Difference between revisions of "Complex multipart regimens"

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The purpose of this page is to capture information about complex comparisons that is not easily conveyed on the treatment regimen pages. Many complex multipart RCTs are of the "Y-shaped" format "A followed by B1 versus B2" or "A1 versus A2 followed by B" and this can be captured on the treatment regimen pages. This page will convey information on more complicated designs, such as "A followed by B versus B followed by A" or "A followed by B versus C followed by D".
 
The purpose of this page is to capture information about complex comparisons that is not easily conveyed on the treatment regimen pages. Many complex multipart RCTs are of the "Y-shaped" format "A followed by B1 versus B2" or "A1 versus A2 followed by B" and this can be captured on the treatment regimen pages. This page will convey information on more complicated designs, such as "A followed by B versus B followed by A" or "A followed by B versus C followed by D".
  
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
  
−
=Breast cancer=
+
=[[Acute myeloid leukemia]]=
−
==BCIRG-005==
+
==COG AAML0531==
 +
 
 +
To be completed
 +
===References===
 +
# Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25092781/ PubMed]
 +
 
 +
==UK MRC AML12==
 +
 
 +
To be completed
 +
===References===
 +
# Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood. 1999 Jun 15;93(12):4131-43. [http://www.bloodjournal.org/content/93/12/4131.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/10361110/ PubMed]
 +
 
 +
==UK MRC AML15==
 +
 
 +
To be completed
 +
===References===
 +
# Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891/ PubMed]
 +
 
 +
=[[Acute promyelocytic leukemia]]=
 +
==C9710==
 +
 
 +
''Note: this trial included a second randomization during the maintenance phase, which is not complex and is therefore not reported here.''
 +
===Arm 1===
 +
*[[Acute_promyelocytic_leukemia#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, Cytarabine, Daunorubicin]], then [[Acute_promyelocytic_leukemia#ATRA_.26_Daunorubicin_2|ATRA & Daunorubicin]]
 +
===Arm 2, with ATO3===
 +
*[[Acute_promyelocytic_leukemia#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, Cytarabine, Daunorubicin]], then [[Acute_promyelocytic_leukemia#Arsenic_trioxide_monotherapy_2|arsenic trioxide]], then [[Acute_promyelocytic_leukemia#ATRA_.26_Daunorubicin_2|ATRA & Daunorubicin]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Without ATO3
 +
|style="background-color:#d73027"|Inferior EFS
 +
|-
 +
|With ATO3
 +
|style="background-color:#1a9850"|Superior EFS
 +
|-
 +
|}
 +
===References===
 +
# Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://www.bloodjournal.org/content/116/19/3751.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20705755/ PubMed]
 +
 
 +
=[[Breast cancer]]=
 +
==DBCG 82b==
 +
 
 +
===Arm 1 (Experimental)===
 +
*[[Mastectomy]], then [[Breast_cancer#CMF|CMF]] x 1, then radiotherapy, then [[Breast_cancer#CMF|CMF]] x 7
 +
===Arm 2 (Control)===
 +
*[[Mastectomy]], then [[Breast_cancer#CMF|CMF]] x 9
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|With RT
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
|Without RT
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|}
 +
===References===
 +
# Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med. 1997 Oct 2;337(14):949-55. [https://doi.org/10.1056/NEJM199710023371401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9395428/ PubMed]
 +
 
 +
==Loesch et al. 2010==
 +
 
 +
===Arm 1, control===
 +
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4
 +
===Arm 2, experimental===
 +
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Doxorubicin_.26_Paclitaxel_.28AT.29|AT (Taxol)]] x 4, then [[#Paclitaxel_monotherapy.2C_weekly_2|wP]] x 12
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|AC-P
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|AP-WP
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|}
 +
===References===
 +
# Loesch D, Greco FA, Senzer NN, Burris HA, Hainsworth JD, Jones S, Vukelja SJ, Sandbach J, Holmes F, Sedlacek S, Pippen J, Lindquist D, McIntyre K, Blum JL, Modiano MR, Boehm KA, Zhan F, Asmar L, Robert N. Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol. 2010 Jun 20;28(18):2958-65. Epub 2010 May 17. [https://doi.org/10.1200/JCO.2009.24.1000 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20479419/ PubMed]
 +
 
 +
==Mavroudis et al. 2017==
 +
 
 
===Arm 1, sequential===
 
===Arm 1, sequential===
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer#Docetaxel_monotherapy_2|T]]
+
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Epirubicin_monotherapy|Epirubicin]], then [[Breast_cancer#Docetaxel_monotherapy_2|Docetaxel]]
 
===Arm 2, concurrent===
 
===Arm 2, concurrent===
−
*[[Breast_cancer#TAC_.28Taxotere.29|TAC]]
+
*[[Surgery#Breast_cancer_surgery|Surgery]], then Docetaxel & Epirubicin
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Schedule'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Sequential
 +
|style="background-color:#d9ef8b"|Might have superior DFS
 +
|-
 +
|Concurrent
 +
|style="background-color:#fee08b"|Might have inferior DFS
 +
|-
 +
|}
 +
===References===
 +
# Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Fountzilas G, Rigas G, Varthalitis I, Kalbakis K, Agelaki S, Hatzidaki D, Georgoulias V. Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group. Br J Cancer. 2017 Jul 11;117(2):164-170. Epub 2017 Jun 22. [https://doi.org/10.1038/bjc.2017.158 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584474/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28641315/ PubMed]
 +
 
 +
==NeoALTTO==
 +
 
 +
===Arm 1, trastuzumab (C)===
 +
*[[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy|Trastuzumab]] x 6 wk, then [[Breast_cancer,_HER2-positive#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy_2|Trastuzumab]] x 34 wk
 +
===Arm 1, lapatinib (E)===
 +
*Lapatinib x 6 wk, then [[Breast_cancer,_HER2-positive#Lapatinib_.26_Paclitaxel_.28TL.29|TL (Taxol)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then Lapatinib x 34 wk
 +
===Arm 3, lapatinib & trastuzumab (E)===
 +
*[[Breast_cancer,_HER2-positive#Lapatinib_.26_Trastuzumab|Lapatinib & Trastuzumab]] x 6 wk, then [[Breast_cancer,_HER2-positive#THL_.28Paclitaxel.29|THL (Taxol)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then [[Breast_cancer,_HER2-positive#Lapatinib_.26_Trastuzumab_2|Lapatinib & Trastuzumab]] x 34 wk
 
===Comparative efficacy===
 
===Comparative efficacy===
−
{| border="1" style="text-align:center;" !align="left"
+
''The primary endpoint was pathologic complete response (pCR) rate. Comparison was only between experimental and control arms (i.e., 2 comparisons).''
−
|'''Schedule'''
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+
!'''Backbone'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|Sequential (AC, then T)
+
|Trastuzumab vs. Lapatinib
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|Concurrent (TAC)
+
|Trastuzumab vs. Lapatinib & Trastuzumab
 +
|style="background-color:#d73027"|Inferior pCR rate
 +
|-
 +
|Lapatinib vs. Trastuzumab
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|Lapatinib & Trastuzumab vs. Trastuzumab
 +
|style="background-color:#1a9850"|Superior pCR rate
 +
|-
 +
|}
 +
===References===
 +
# Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed]
 +
## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed]
 +
 +
==NOAH==
 +
 +
===Arm 1, no trastuzumab (Control)===
 +
*AT (Taxol) x 3, then T (Taxol) x 3, then CMF x 3, then [[surgery]]
 +
===Arm 2, with trastuzumab (Experimental)===
 +
*ATH (Paclitaxel) x 3, then [[Breast_cancer,_HER2-positive#Paclitaxel_.26_Trastuzumab_.28TH.29|TH]] x 3, then CMF & H x 3, then [[surgery]], then [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy_2|trastuzumab for a total of 1 year]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
|'''Sequencing'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|With trastuzumab
 +
|style="background-color:#91cf60"|Seems to have superior EFS
 +
|-
 +
|No trastuzumab
 +
|style="background-color:#fc8d59"|Seems to have inferior EFS
 +
|-
 +
|}
 +
===References===
 +
# Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. [https://doi.org/10.1016/S0140-6736(09)61964-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20113825/ PubMed]
 +
## '''Update:''' Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzù D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 May;15(6):640-7. Epub 2014 Mar 20. Erratum in: Lancet Oncol. 2018 Dec;19(12):e667. [https://doi.org/10.1016/S1470-2045(14)70080-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24657003/ PubMed]
 +
 +
==PREPARE==
 +
 +
===Arm 1, control===
 +
*[[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4, then [[Surgery#Breast_cancer_surgery|surgery]]
 +
===Arm 2, experimental===
 +
*ddE x 3, then ddT (Taxol) x 3, then CMF x 3, then [[Surgery#Breast_cancer_surgery|surgery]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Control
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|Experimental
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|}
 +
===References===
 +
# Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Beckmann MW, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Nekljudova V, Lebeau A, Loibl S, Fasching PA; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer--outcome on prognosis. Ann Oncol. 2011 Sep;22(9):1999-2006. Epub 2011 Mar 7. [https://doi.org/10.1093/annonc/mdq713 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21382868/ PubMed]
 +
 +
==Recht et al. 1996==
 +
 +
===Arm 1, chemo first===
 +
*[[Surgery#Lumpectomy|Lumpectomy]], then [[Breast_cancer_-_historical#CAMFP|CAMFP]], then RT
 +
===Arm 2, RT first===
 +
*[[Surgery#Lumpectomy|Lumpectomy]], then RT, then [[Breast_cancer_-_historical#CAMFP|CAMFP]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 50%"|'''anti-HER2 medication'''
 +
!style="width: 50%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|Chemo first
 +
| style="background-color:#91cf60" |Seems to have superior MFS
 +
|-
 +
|RT first
 +
| style="background-color:#fc8d59" |Seems to have inferior MFS
 +
|-
 +
|}
 +
===References===
 +
# Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. [https://doi.org/10.1056/NEJM199605233342102 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8614420/ PubMed]
 +
 +
==SBG 9401==
 +
 +
===Arm 1 (control)===
 +
*[[Surgery]], then [[Breast_cancer#FEC_2|FEC]] x 2, then HD-FEC x 1, then [[Breast_cancer_-_historical#CTCb.2C_then_auto_HSCT|CTCb with auto HSCT]]
 +
===Arm 2 (experimental)===
 +
*Tailored FEC x 6
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Control
 +
| style="background-color:#fc8d59" |Seems to have inferior RFS
 +
|-
 +
|Experimental
 +
| style="background-color:#91cf60" |Seems to have superior RFS
 
|-
 
|-
 
|}
 
|}
 
===References===
 
===References===
−
# Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. [http://jco.ascopubs.org/content/29/29/3877.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21911726 PubMed]
+
# Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group 9401 study. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. [https://doi.org/10.1016/s0140-6736(00)02841-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11052580/ PubMed]
  
−
==BCIRG 006==
+
==SWOG-8814==
−
===Arm 1, sequential without trastuzumab===
+
 
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer#Docetaxel_monotherapy_2|T]]
+
===Arm 1 (Control)===
−
===Arm 2, sequential with trastuzumab===
+
*[[Surgery]], then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|tamoxifen]] x 5 y
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer,_HER-2_positive#TH_.28Taxotere.29_2|TH]]
+
===Arm 2, CAF-T (Experimental)===
−
===Arm 3, concurrent with trastuzumab===
+
*[[Surgery]], then [[Breast_cancer#FAC_2|CAF]] x 6, then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|tamoxifen]] x 5 y
−
*[[Breast_cancer,_HER-2_positive#TCH_.28Taxotere.2C_Carboplatin.29|TCH]]
+
===Arm 3, CAFT (Experimental)===
 +
*[[Surgery]], then CAFT
 
===Comparative efficacy===
 
===Comparative efficacy===
−
*Analyzed using a step-down design
 
 
====Comparison 1====
 
====Comparison 1====
−
{| border="1" style="text-align:center;" !align="left"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
|'''Trastuzumab-containing regimens vs. AC, then T'''
+
!'''Design'''
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|No chemotherapy
 +
| style="background-color:#fee08b" |Might have inferior OS
 +
|-
 +
|With chemotherapy
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|}
 +
====Comparison 2====
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Timing'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Concurrent (CAFT)
 +
| style="background-color:#fee08b" |Might have inferior DFS
 +
|-
 +
|Sequential (CAF-T)
 +
| style="background-color:#d9ef8b" |Might have superior DFS
 +
|-
 +
|}
 +
===References===
 +
# Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. Epub 2009 Dec 10. [https://doi.org/10.1016/S0140-6736(09)61523-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20004966/ PubMed]
 +
 
 +
==TRYPHAENA==
 +
 
 +
===Arm A===
 +
*FEC & HP x 3, then [[Breast_cancer,_HER2-positive#THP_.28Docetaxel.29|THP]] x 3, then [[surgery]]
 +
===Arm B===
 +
*[[Breast_cancer#FEC|FEC]] x 3, then [[Breast_cancer,_HER2-positive#THP_.28Docetaxel.29|THP]] x 3, then [[surgery]]
 +
===Arm C===
 +
*[[Breast_cancer,_HER2-positive#TCHP_.28Docetaxel.29|TCHP]] x 6, then [[surgery]]
 +
===Comparative efficacy===
 +
''Note: this was a cardiac safety study; efficacy findings are not reported.''
 +
===References===
 +
# Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. [https://doi.org/10.1093/annonc/mdt182 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23704196/ PubMed]
 +
 
 +
=Cervical cancer=
 +
==NOGGO-AGO==
 +
 
 +
===Arm 1 (Control)===
 +
*[[Surgery]], then [[Cervical_cancer#Carboplatin_.26_Ifosfamide|adjuvant Carboplatin & Ifosfamide]] x 4, then [[Cervical_cancer#Radiation_therapy_2|EBRT]]
 +
===Arm 2 (Experimental)===
 +
*[[Surgery]], then adjuvant Carboplatin, Ifosfamide, Erythropoietin alfa, then EBRT & Erythropoietin alfa
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|No EPO
 +
|style="background-color:#fee08b"|Might have inferior RFS
 +
|-
 +
|With EPO
 +
|style="background-color:#d9ef8b"|Might have superior RFS
 +
|-
 +
|}
 +
 
 +
===References===
 +
# Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2010.30.4899 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21860000/ PubMed]
 +
 
 +
=[[Colorectal cancer]]=
 +
==CAIRO==
 +
 
 +
===Arm 1, sequential single agent (Control)===
 +
*[[Colon_cancer#Capecitabine_monotherapy_2|First-line capecitabine]], then [[Colon_cancer#Irinotecan_monotherapy_2|second-line irinotecan]], then [[Colon_cancer#CapeOx_4|third-line CapeOx]]
 +
===Arm 2, sequential combinations (Experimental)===
 +
*[[Colon_cancer#CAPIRI|First-line CAPIRI]], then [[Colon_cancer#CapeOx_3|second-line CapeOx]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Approach'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Sequential single agent
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|Sequential combinations
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|}
 +
===References===
 +
# Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, de Jong RS, Rodenburg CJ, Vreugdenhil G, Loosveld OJ, van Bochove A, Sinnige HA, Creemers GM, Tesselaar ME, Slee PHTJ, Werter MJ, Mol L, Dalesio O, Punt CJ. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007 Jul 14;370(9582):135-142. [https://doi.org/10.1016/s0140-673607610861 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17630036/ PubMed]
 +
 
 +
==FFCD 2000-05==
 +
 
 +
===Arm 1, sequential (Control)===
 +
*[[Colon_cancer#Fluorouracil_.26_Folinic_acid_2|First-line sLV5FU2]], then [[Colon_cancer#mFOLFOX6_4|second-line mFOLFOX6]], then [[Colon_cancer#FOLFIRI_4|third-line FOLFIRI]]
 +
===Arm 2, combination (Experimental)===
 +
*[[Colon_cancer#mFOLFOX6_3|First-line mFOLFOX6]], then [[Colon_cancer#FOLFIRI_3|second-line FOLFIRI]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Approach'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
![[Levels_of_Evidence#Toxicity|Toxicity]]
 +
|-
 +
|Sequential
 +
| style="background-color:#ffffbf" |Seems not superior
 +
| style="background-color:#1a9850" |Less toxic
 +
|-
 +
|Combination
 +
| style="background-color:#ffffbf" |Seems not superior
 +
| style="background-color:#d73027" |More toxic
 +
|-
 +
|}
 +
===References===
 +
# Ducreux M, Malka D, Mendiboure J, Etienne PL, Texereau P, Auby D, Rougier P, Gasmi M, Castaing M, Abbas M, Michel P, Gargot D, Azzedine A, Lombard-Bohas C, Geoffroy P, Denis B, Pignon JP, Bedenne L, Bouché O; Fédération Francophone de Cancérologie Digestive (FFCD) 2000–05 Collaborative Group. Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial. Lancet Oncol. 2011 Oct;12(11):1032-44. Epub 2011 Sep 6. [https://doi.org/10.1016/s1470-2045(11)70199-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21903473/ PubMed]
 +
 
 +
=[[Diffuse large B-cell lymphoma]]=
 +
==SWOG S8736==
 +
 
 +
===Arm 1 - Control===
 +
*[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 8
 +
===Arm 2 - Experimental===
 +
*[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, then [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] x 40 to 5500 cGy
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|CHOP x 8
 +
|style="background-color:#fc8d59"|Seems to have inferior OS
 +
|-
 +
|CHOP x 3, then RT
 +
|style="background-color:#91cf60"|Seems to have superior OS
 +
|-
 +
|}
 +
===References===
 +
# Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. [https://doi.org/10.1056/NEJM199807023390104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9647875/ PubMed]
 +
 
 +
=[[Endometrial cancer]]=
 +
==PORTEC-3==
 +
 
 +
===Arm 1 - Control===
 +
*[[Surgery#Endometrial_cancer_surgery|Surgery]], then [[Endometrial_cancer#Radiation_therapy|RT]]
 +
===Arm 2 - Experimental===
 +
*[[Surgery#Endometrial_cancer_surgery|Surgery]], then [[Endometrial_cancer#Cisplatin_.26_RT|Cisplatin & RT]], then [[Endometrial_cancer#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]]
 +
===Comparative efficacy===
 +
{| class="wikitable" style="width: 40%; text-align:center;"
 +
!style="width: 50%"|Modality
 +
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Radiotherapy
 +
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 +
|-
 +
|Chemoradiotherapy
 +
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2019 update.''
 +
===References===
 +
# de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. Epub 2018 Feb 12. [https://doi.org/10.1016/S1470-2045(18)30079-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840256/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29449189/ PubMed]
 +
## '''Update:''' de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Gribaudo S, Provencher D, Hanzen C, Kruitwagen RF, Smit VTHBM, Singh N, Do V, Lissoni A, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019 Sep;20(9):1273-1285. Epub 2019 Jul 22. Erratum in: Lancet Oncol. 2019 Sep;20(9):e468. [https://doi.org/10.1016/S1470-2045(19)30395-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/31345626/ PubMed]
 +
 
 +
=[[Follicular lymphoma]]=
 +
==GALLIUM==
 +
 
 +
===Arm 1 - Control===
 +
*[[Follicular_lymphoma#Bendamustine_.26_Rituximab_.28BR.29|BR]] x 6 or [[Follicular_lymphoma#R-CHOP|R-CHOP]] x 8 or [[Follicular_lymphoma#R-CVP|R-CVP]] x 8, then [[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance x 2 y
 +
===Arm 2 - Experimental===
 +
*[[Follicular_lymphoma#Bendamustine_.26_Obinutuzumab|Bendamustine & Obinutuzumab]] x 6 or [[Follicular_lymphoma#G-CHOP|G-CHOP]] x 8 or [[Follicular_lymphoma#G-CVP|G-CVP]] x 8, then [[Follicular_lymphoma#Obinutuzumab_monotherapy|Obinutuzumab]] maintenance x 2y
 +
===Comparative efficacy===
 +
{| class="wikitable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|mAb
 +
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
!style="width: 33%"|[[Levels_of_Evidence#Toxicity|Toxicity]]
 +
|-
 +
|Rituximab-chemotherapy
 +
| style="background-color:#d73027" |Inferior PFS
 +
| style="background-color:#1a9850" |Superior toxicity
 +
|-
 +
|Obinutuzumab-chemotherapy
 +
| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>PFS36: 80% vs 73%<br>(HR 0.66, 95% CI 0.51-0.85)
 +
| style="background-color:#d73027" |Inferior toxicity
 +
|-
 +
|}
 +
 
 +
===References===
 +
# Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] [https://pubmed.ncbi.nlm.nih.gov/28976863/ PubMed]
 +
 
 +
=Gastroesophageal cancer=
 +
==POET==
 +
 
 +
===Arm 1===
 +
*[[Esophageal_cancer#CLF|PLF]] x 15 wk, then [[surgery]]
 +
===Arm 2===
 +
*[[Esophageal_cancer#CLF|PLF]] x 12 wk, then [[Esophageal_cancer#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]], then [[surgery]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Neoadjuvant chemotherapy only
 +
|style="background-color:#fee08b"|Might have inferior OS
 +
|-
 +
|Neoadjuvant chemotherapy and chemoradiotherapy
 +
|style="background-color:#d9ef8b"|Might have superior OS
 +
|-
 +
|}
 +
===References===
 +
# Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. [https://doi.org/10.1200/JCO.2008.17.0506 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19139439/ PubMed]
 +
 
 +
==PRODIGE5/ACCORD17==
 +
 
 +
===Arm 1 - Control===
 +
*[[Esophageal_cancer#Cisplatin_.26_Fluorouracil_.28CF.29_.26_RT_2|Definitive CF & RT]], then [[Esophageal_cancer#Cisplatin_.26_Fluorouracil_.28CF.29_2|CF]] x 2
 +
===Arm 2 - Experimental===
 +
*[[Esophageal_cancer#FOLFOX4_.26_RT|Definitive FOLFOX4 & RT]], then [[Esophageal_cancer#FOLFOX4|FOLFOX4]] x 3
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|CF-based
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|FOLFOX4-based
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|}
 +
===References===
 +
# Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. [https://doi.org/10.1016/S1470-2045(14)70028-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24556041/ PubMed]
 +
 
 +
=[[Glioblastoma]]=
 +
==AVAglio==
 +
 
 +
===Arm 1, control===
 +
*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|temozolomide]] maintenance
 +
===Arm 2, experimental===
 +
*[[Surgery]], then adjuvant temozolomide, bevacizumab, RT, then temozolomide & bevacizumab maintenance, then bevacizumab maintenance
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Temozolomide alone
 +
|style="background-color:#d73027"|Inferior PFS
 +
|-
 +
|Bevacizumab-containing arm
 +
|style="background-color:#1a9850"|Superior PFS
 +
|-
 +
|}
 +
===References===
 +
# Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. [https://doi.org/10.1056/NEJMoa1308345 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24552318/ PubMed]
 +
 
 +
==EORTC 22981/26981; NCIC-CTG CE.3==
 +
 
 +
===Arm 1, control===
 +
*[[Surgery]], then [[Glioblastoma#Radiation_therapy|adjuvant radiotherapy]]
 +
===Arm 2, experimental===
 +
*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant Temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|Temozolomide]] maintenance
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Radiotherapy alone
 +
|style="background-color:#d73027"|Inferior OS
 +
|-
 +
|Temozolomide-containing arm
 +
|style="background-color:#1a9850"|Superior OS
 +
|-
 +
|}
 +
===References===
 +
# Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; [[Study_Groups#EORTC|EORTC]] Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. [https://doi.org/10.1056/NEJMoa043330 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15758009/ PubMed]
 +
 
 +
==RTOG 0825==
 +
 
 +
===Arm 1, control===
 +
*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant Temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|Temozolomide]] maintenance
 +
===Arm 2, experimental===
 +
*[[Surgery]], then adjuvant Temozolomide, Bevacizumab, RT, then Temozolomide & Bevacizumab maintenance
 +
===Comparative efficacy===
 +
''Note: although the control regimen had inferior PFS, the effect size did not reach the prespecified improvement target.''
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Temozolomide alone
 +
|style="background-color:#d73027"|Inferior PFS
 +
|-
 +
|Bevacizumab-containing arm
 +
|style="background-color:#1a9850"|Superior PFS (co-primary endpoint)
 +
|-
 +
|}
 +
 
 +
===References===
 +
# Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. [https://doi.org/10.1056/NEJMoa1308573 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201043/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552317/ PubMed]
 +
 
 +
=[[Head and neck cancer]]=
 +
==EORTC 24954==
 +
 
 +
===Arm 1, control===
 +
*[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29|CF]] x 4, then [[Head_and_neck_cancer#Radiation_therapy|RT]]
 +
===Arm 2, experimental===
 +
*[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29_.26_RT|CF/RT]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Sequential RT
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|Alternating RT
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|}
 +
===References===
 +
# Lefebvre JL, Rolland F, Tesselaar M, Bardet E, Leemans CR, Geoffrois L, Hupperets P, Barzan L, de Raucourt D, Chevalier D, Licitra L, Lunghi F, Stupp R, Lacombe D, Bogaerts J, Horiot JC, Bernier J, Vermorken JB; [[Study_Groups#EORTC|EORTC]] Head and Neck Cancer Cooperative Group; [[Study_Groups#EORTC|EORTC]] Radiation Oncology Group. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009 Feb 4;101(3):142-52. Epub 2009 Jan 27. [https://academic.oup.com/jnci/article/101/3/142/947754 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724854/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19176454/ PubMed]
 +
 
 +
==RTOG 91-11==
 +
===Arm 1, induction chemotherapy, then radiotherapy (Control)===
 +
*[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29|PF]] x 3, then [[Head_and_neck_cancer#Radiation_therapy|RT]]
 +
===Arm 2, concurrent chemoradiotherapy (Experimental)===
 +
*[[Head_and_neck_cancer#Cisplatin_.26_RT|Cisplatin & RT]]
 +
===Arm 3, radiotherapy (Experimental)===
 +
*[[Head_and_neck_cancer#Radiation_therapy|RT]]
 +
===Comparative efficacy===
 +
''Efficacy is based on the 2012 update.''
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen vs.'''
 +
!'''Arm 1'''
 +
!'''Arm 2'''
 +
!'''Arm 3'''
 +
|-
 +
|Arm 1 vs.
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d73027" |Inferior LFS
 +
| style="background-color:#91cf60" |Seems to have superior LFS
 +
|-
 +
|Arm 2 vs.
 +
| style="background-color:#1a9850" |Superior LFS
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#91cf60" |Seems to have superior LFS
 +
|-
 +
|Arm 3 vs.
 +
| style="background-color:#fc8d59" |Seems to have inferior LFS
 +
| style="background-color:#fc8d59" |Seems to have inferior LFS
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|}
 +
===References===
 +
# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [https://doi.org/10.1056/NEJMoa031317 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14645636/ PubMed]
 +
## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [https://doi.org/10.1200/jco.2012.43.6097 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577950/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23182993/ PubMed]
 +
 
 +
=[[Classical Hodgkin lymphoma]]=
 +
==EORTC-GELA H8-F==
 +
 
 +
===Arm 1===
 +
*[[Classical_Hodgkin_lymphoma#MOPP-ABV|MOPP-ABV]] x 3, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
 +
===Arm 2===
 +
*[[Classical_Hodgkin_lymphoma#Radiotherapy|STNI]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|AC, then TH
+
|MOPP-ABV x 3, then IFRT
 
|style="background-color:#1a9850"|Superior OS
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|-
−
|TCH
+
|STNI
 +
|style="background-color:#d73027"|Inferior OS
 +
|-
 +
|}
 +
===References===
 +
# Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; [[Study_Groups#EORTC|EORTC]]; GELA. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. [https://doi.org/10.1056/NEJMoa064601 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/17989384/ PubMed]
 +
 
 +
==EORTC-GELA H8-U==
 +
 
 +
===Arm 1===
 +
*[[Classical_Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 4, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
 +
===Arm 2===
 +
*[[Classical_Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 4, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|STNI]]
 +
===Arm 3 (control)===
 +
*[[Classical_Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 6, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
 +
===Comparative efficacy===
 +
''Note: the paper describes this as an equivalence study, although the primary endpoint of EFS had p=0.80.''
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|MOPP-ABV x 4, then IFRT
 +
|style="background-color:#ffffbf"|Inconclusive whether equivalent
 +
|-
 +
|MOPP-ABV x 4, then STNI
 +
|style="background-color:#ffffbf"|Inconclusive whether equivalent
 +
|-
 +
|MOPP-ABV x 6, then IFRT
 +
|style="background-color:#ffffbf"|Inconclusive whether equivalent
 +
|-
 +
|}
 +
===References===
 +
# Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; [[Study_Groups#EORTC|EORTC]]-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. [https://doi.org/10.1056/NEJMoa064601 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/17989384/ PubMed]
 +
 
 +
==EORTC/LYSA/FIL H10==
 +
 
 +
''Note: randomization in this trial occurred before treatment, but took effect after 2 cycles of ABVD, and only if interim PET-CT was negative.''
 +
===Arm 1===
 +
*Favorable: [[Classical_Hodgkin_lymphoma#ABVD|ABVD]] x 4
 +
*Unfavorable: [[Classical_Hodgkin_lymphoma#ABVD|ABVD]] x 6
 +
===Arm 2===
 +
*Favorable: [[Classical_Hodgkin_lymphoma#ABVD|ABVD]] x 3, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|INRT]]
 +
*Unfavorable: [[Classical_Hodgkin_lymphoma#ABVD|ABVD]] x 4, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|INRT]]
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|ABVD x 4
 +
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
 +
|-
 +
|ABVD x 3, then INRT
 +
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
 +
|-
 +
|}
 +
===References===
 +
# Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. [https://doi.org/10.1200/jco.2013.51.9298 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24637998/ PubMed]
 +
## '''Update:''' André MPE, Girinsky T, Federico M, Reman O, Fortpied C, Gotti M, Casasnovas O, Brice P, van der Maazen R, Re A, Edeline V, Fermé C, van Imhoff G, Merli F, Bouabdallah R, Sebban C, Specht L, Stamatoullas A, Delarue R, Fiaccadori V, Bellei M, Raveloarivahy T, Versari A, Hutchings M, Meignan M, Raemaekers J. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2017 Jun 1;35(16):1786-1794. Epub 2017 Mar 14. [https://doi.org/10.1200/JCO.2016.68.6394 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28291393/ PubMed]
 +
 
 +
==GHSG HD17==
 +
 
 +
===Arm 1 (Control)===
 +
*[[Classical_Hodgkin_lymphoma#eBEACOPP|eBEACOPP]] x 2, then [[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 2, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 3000 cGy
 +
===Arm 2 (Experimental)===
 +
*PET4 positive: [[Classical_Hodgkin_lymphoma#eBEACOPP|eBEACOPP]] x 2, then [[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 2, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 3000 cGy
 +
*PET4 negative: [[Classical_Hodgkin_lymphoma#eBEACOPP|eBEACOPP]] x 2, then [[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 2
 +
 
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 40%; text-align:center;"
 +
!style="width: 50%"|Chemotherapy
 +
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|2+2 -> IFRT
 +
| style="background-color:#eeee01" |Non-inferior PFS
 +
|-
 +
|PET-guided therapy
 +
| style="background-color:#eeee01" |Non-inferior PFS
 +
|-
 +
|}
 +
===References===
 +
# Borchmann P, Plütschow A, Kobe C, Greil R, Meissner J, Topp MS, Ostermann H, Dierlamm J, Mohm J, Thiemer J, Sökler M, Kerkhoff A, Ahlborn M, Halbsguth TV, Martin S, Keller U, Balabanov S, Pabst T, Vogelhuber M, Hüttmann A, Wilhelm M, Zijlstra JM, Moccia A, Kuhnert G, Bröckelmann PJ, von Tresckow B, Fuchs M, Klimm B, Rosenwald A, Eich H, Baues C, Marnitz S, Hallek M, Diehl V, Dietlein M, Engert A. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):223-234. [https://doi.org/10.1016/s1470-2045(20)30601-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539742/ PubMed] [https://clinicaltrials.gov/study/NCT01356680 NCT01356680]
 +
 
 +
==NCIC-CTG/ECOG HD.6==
 +
 
 +
''Note: this randomization was for patients with unfavorable risk.''
 +
===Arm 1===
 +
*[[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 4
 +
===Arm 2===
 +
*[[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 2, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|STNI]]
 +
===Comparative efficacy===
 +
''Efficacy is based on the 2011 update.''
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|ABVD x 4
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|style="background-color:#91cf60"|Seems to have superior OS
 +
|-
 +
|ABVD x 2, then STNI
 +
|style="background-color:#fc8d59"|Seems to have inferior OS
 +
|-
 +
|}
 +
===References===
 +
# Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Bezjak A, Wells WA, Burns BF, Winter JN, Horning SJ, Dar AR, Djurfeldt MS, Ding K, Shepherd LE; National Cancer Institute of Canada Clinical Trials Group; [[Study_Groups#ECOG|ECOG]]. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005 Jul 20;23(21):4634-42. Epub 2005 Apr 18. [https://doi.org/10.1200/JCO.2005.09.085 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15837968/ PubMed]
 +
## '''Update:''' Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; [[Study_Groups#ECOG|ECOG]]. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. [https://doi.org/10.1056/NEJMoa1111961 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22149921/ PubMed]
 +
 +
=[[Mantle cell lymphoma]]=
 +
==MCL Younger==
 +
===Arm 1 (Control)===
 +
*[[Mantle_cell_lymphoma#R-CHOP|R-CHOP]] x 6, then [[Stem_cell_mobilization#DexaBEAM_.26_G-CSF|Dexa-BEAM]], then [[Mantle_cell_lymphoma#Cyclophosphamide_.26_TBI.2C_then_auto_HSCT|Cy/TBI auto HSCT]]
 +
===Arm 2 (Experimental)===
 +
*[[Mantle_cell_lymphoma#R-CHOP.2FR-DHAP|R-CHOP/R-DHAP]] x 6, then cytarabine, melphalan, TBI auto HSCT
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 50%"|Regimen
 +
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|SOC
 +
| style="background-color:#fc8d59" |Seems to have inferior TTTF
 +
|-
 +
|Cytarabine-based
 +
|style="background-color:#91cf60"|Seems to have superior TTTF
 +
|-
 +
|}
 +
===References===
 +
# Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. Epub 2016 Jun 14. [https://doi.org/10.1016/S0140-6736(16)00739-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/27313086/ PubMed]
 +
##'''Update:''' Hermine O, Jiang L, Walewski J, Bosly A, Thieblemont C, Szymczyk M, Pott C, Salles G, Feugier P, Hübel K, Haioun C, Casasnovas RO, Schmidt C, Bouabdallah K, Ribrag V, Kanz L, Dürig J, Metzner B, Sibon D, Cheminant M, Burroni B, Klapper W, Hiddemann W, Unterhalt M, Hoster E, Dreyling M; European Mantle Cell Lymphoma Network. High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023 Jan 20;41(3):479-484. Epub 2022 Dec 5. [https://doi.org/10.1200/jco.22.01780 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36469833/ PubMed]
 +
 +
=[[Multiple myeloma]]=
 +
==HOVON-50==
 +
===Arm 1 (Control)===
 +
*[[Multiple_myeloma_-_historical#VAD|VAD]], then [[Stem_cell_mobilization#CAD_.26_G-CSF|CAD & G-CSF stem cell mobilization]], then [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan_monotherapy.2C_then_auto_HSCT|single]] or [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem]] melphalan auto HSCT, then [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|interferon alfa]] maintenance
 +
===Arm 2 (Experimental)===
 +
*[[Multiple_myeloma,_induction#TAD_.28Thalidomide.29|TAD]] x 3, then [[Stem_cell_mobilization#CAD_.26_G-CSF|CAD & G-CSF stem cell mobilization]], then [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan_monotherapy.2C_then_auto_HSCT|single]] or [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem]] melphalan auto HSCT, then [[Multiple_myeloma,_consolidation_and_maintenance#Thalidomide_monotherapy|thalidomide]] maintenance
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 50%"|Regimen
 +
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|SOC
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|Thalidomide-based
 +
| style="background-color:#1a9850" |Superior PFS
 
|-
 
|-
 
|}
 
|}
−
====Comparison 2====
+
===References===
−
{| border="1" style="text-align:center;" !align="left"
+
# Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [http://www.bloodjournal.org/content/115/6/1113 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19880501/ PubMed]
−
|'''Trastuzumab-containing regimens'''
+
## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https://doi.org/10.1016/S2352-3026(18)30149-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290905/ PubMed]
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+
 
 +
=[[Non-small cell lung cancer]]=
 +
==ECOG 3598==
 +
 
 +
===Arm 1 (Control)===
 +
*[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_.28CP.29_2|PC]] induction, then [[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_.28CP.29_.26_RT|Carboplatin, Paclitaxel, RT]]
 +
===Arm 2, with thalidomide (Experimental)===
 +
*TPC, then Carboplatin, Paclitaxel, Thalidomide, RT
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|AC, then TH
+
|Without thalidomide
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|TCH
+
|With thalidomide
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
 
===References===
 
===References===
−
# Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. [http://www.nejm.org/doi/full/10.1056/NEJMoa0910383 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21991949 PubMed]
+
# Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.36.9116 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295560/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22271472/ PubMed]
  
−
==CALGB 9741==
+
==IUNO==
−
''Note: what is referred to in this study as concurrent is in fact the same regimen that is referred to as sequential in other studies.''
+
 
−
===Arm 1, sequential===
+
===Arm 1, "early" erlotinib===
−
*A, then [[Breast_cancer#Paclitaxel_monotherapy_2|T]], then C
+
*[[Non-small_cell_lung_cancer#Erlotinib_monotherapy|Maintenance erlotinib]]
−
===Arm 2, dose-dense sequential===
+
===Arm 2, "late" erlotinib===
−
*ddA, then [[Breast_cancer#Paclitaxel_monotherapy_2|ddT]], then ddC
+
*[[Non-small_cell_lung_cancer#Placebo_3|Placebo]] until progression or intolerance, then [[Non-small_cell_lung_cancer#Erlotinib_monotherapy_2|erlotinib]]
−
===Arm 3, "concurrent"===
+
===Comparative efficacy===
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer#Paclitaxel_monotherapy_2|T]]
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
===Arm 4, dose-dense "concurrent"===
+
!'''Timing'''
−
*[[Breast_cancer#ddAC_2|ddAC]], then [[Breast_cancer#Paclitaxel_monotherapy_2|ddT]]
+
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Maintenance erlotinib
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 +
|-
 +
|Second-line erlotinib
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
===References===
 +
# Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [https://doi.org/10.1016/j.lungcan.2016.10.007 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27987585/ PubMed]
 +
 
 +
==RTOG 9410==
 +
 
 +
===Arm 1, sequential (control)===
 +
*[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinblastine_2|Cisplatin & Vinblastine]], then [[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
 +
===Arm 2, concurrent (experimental)===
 +
*[[Non-small_cell_lung_cancer#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]]
 +
===Arm 3, concurrent (experimental)===
 +
*[[Non-small_cell_lung_cancer#Cisplatin.2C_Vinblastine.2C_RT|Cisplatin, Vinblastine, RT]]
 
===Comparative efficacy===
 
===Comparative efficacy===
−
*Analyzed using a 2 x 2 factorial design
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
====Comparison 1====
+
!'''Schedule'''
−
{| border="1" style="text-align:center;" !align="left"
+
![[Levels_of_Evidence#Efficacy|Efficacy]]
−
|'''Dose density'''
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
 
|-
 
|-
−
|Dose-dense (q2wk)
+
|Concurrent
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|-
 
|-
−
|Standard (q3wk)
+
|Sequential
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
−
====Comparison 2====
+
===References===
−
{| border="1" style="text-align:center;" !align="left"  
+
# Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21903745/ PubMed]
−
|'''Schedule'''
+
 
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+
=[[Ovarian cancer]]=
 +
==GOG 114==
 +
 
 +
===Arm 1 - Control===
 +
*[[Ovarian_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] x 6
 +
===Arm 2 - Experimental===
 +
*[[Ovarian_cancer#Carboplatin_monotherapy|Carboplatin]] AUC 9 x 2, then [[Ovarian_cancer#IP_Cisplatin_.26_Paclitaxel|IP Cisplatin & IV Paclitaxel]] x 6
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 50%"|'''Regimen'''
 +
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Control
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|Experimental
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|}
 +
===References===
 +
# Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. [https://doi.org/10.1200/JCO.2001.19.4.1001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11181662/ PubMed]
 +
 
 +
=[[Pancreatic cancer]]=
 +
==GERCOR LAP07==
 +
 
 +
''This study had two randomizations; the second only occurred if patients were progression-free after 4 cycles.''
 +
===Arm 1 - Control===
 +
*[[Pancreatic_cancer#Gemcitabine_monotherapy_2|Gemcitabine]] x 6
 +
===Arm 2 - Experimental===
 +
*[[Pancreatic_cancer#Gemcitabine_monotherapy_2|Gemcitabine]] x 4, then Capecitabine & RT
 +
===Arm 3 - Experimental===
 +
*[[Pancreatic_cancer#Erlotinib_.26_Gemcitabine|Erlotinib & Gemcitabine]] x 6
 +
===Arm 4 - Experimental===
 +
*[[Pancreatic_cancer#Erlotinib_.26_Gemcitabine|Erlotinib & Gemcitabine]] x 4, then Capecitabine, Erlotinib, RT
 +
===Comparative efficacy===
 +
====First randomization====
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Gemcitabine
 +
|style="background-color:#d9ef8b"|Might have superior OS
 +
|-
 +
|With Erlotinib
 +
|style="background-color:#fee08b"|Might have inferior OS
 +
|-
 +
|}
 +
====Second randomization====
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Modality'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|Concurrent
+
|Chemotherapy
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|Sequential
+
|Chemoradiotherapy
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
 
===References===
 
===References===
−
# Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. [http://jco.ascopubs.org/content/21/8/1431.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12668651 PubMed]
+
# Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. [https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.4324 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27139057/ PubMed]
 +
 
 +
=[[Rectal cancer]]=
 +
==CinClare==
 +
===Arm 1 (Control)===
 +
[[Rectal_cancer#Capecitabine_.26_RT|Capecitabine & RT]], then [[Rectal_cancer#CapeOx|CapeOx]] x 1, then TME, then CapeOx x 5
 +
 
 +
===Arm 2 (Experimental)===
 +
Genotype-dosed CAPIRI & RT, then genotype-dosed CAPIRI x 1, then TME, then CapeOx x 5
 +
 
 +
===Comparative efficacy===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!'''Regimen'''
 +
![[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|Control
 +
| style="background-color:#d73027" |Inferior pCR rate
 +
|-
 +
|Experimental
 +
| style="background-color:#1a9850" |Superior pCR rate
 +
|-
 +
|}
 +
===References===
 +
#Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. [https://doi.org/10.1200/jco.20.01932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33119477/ PubMed] [https://clinicaltrials.gov/study/NCT02605265 NCT02605265]
 +
 
 +
==RAPIDO==
 +
===Arm 1 (Control)===
 +
[[Rectal_cancer#Capecitabine_.26_RT|Capecitabine & RT]], then TME, then (per hospital policy) CapeOx x 8 or FOLFOX4 x 12
 +
 
 +
===Arm 2 (Experimental)===
 +
[[Rectal_cancer#Radiation_therapy|RT]], then [[Rectal_cancer#CapeOx|CapeOx]] x 6 or [[Rectal_cancer#FOLFOX4|FOLFOX4]] x 9, then TME
  
−
==GEICAM 9906==
 
−
===Arm 1===
 
−
*[[Breast_cancer#FEC_2|FEC]] x 6
 
−
===Arm 2===
 
−
*[[Breast_cancer#FEC_2|FEC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy_2|T]]
 
 
===Comparative efficacy===
 
===Comparative efficacy===
−
{| border="1" style="text-align:center;" !align="left"
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
|'''Regimen'''
+
!'''Regimen'''
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|FEC x 6
+
|RT, then chemo, then TME
−
|style="background-color:#d73027"|Inferior DFS
+
| style="background-color:#91cf60" |Seems to have superior DRTF
 
|-
 
|-
−
|FEC x 4, then T
+
|Chemo-RT, then TME, +/- adjuvant chemo
−
|style="background-color:#1a9850"|Superior DFS
+
| style="background-color:#fc8d59" |Seems to have inferior DRTF
 
|-
 
|-
 
|}
 
|}
 
===References===
 
===References===
−
# Martín M, Rodríguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Munárriz B, Rodríguez CA, Crespo C, de Alava E, López García-Asenjo JA, Guitián MD, Almenar S, González-Palacios JF, Vera F, Palacios J, Ramos M, Gracia Marco JM, Lluch A, Alvarez I, Seguí MA, Mayordomo JI, Antón A, Baena JM, Plazaola A, Modolell A, Pelegrí A, Mel JR, Aranda E, Adrover E, Alvarez JV, García Puche JL, Sánchez-Rovira P, Gonzalez S, López-Vega JM; GEICAM 9906 Study Investigators. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst. 2008 Jun 4;100(11):805-14. Epub 2008 May 27. [http://jnci.oxfordjournals.org/content/100/11/805.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18505968 PubMed]
+
#Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. [https://doi.org/10.1016/s1470-2045(20)30555-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33301740/ PubMed]
 +
 
  
 
[[Category:General reference pages]]
 
[[Category:General reference pages]]

Revision as of 11:09, 25 May 2024

Back to Top

The purpose of this page is to capture information about complex comparisons that is not easily conveyed on the treatment regimen pages. Many complex multipart RCTs are of the "Y-shaped" format "A followed by B1 versus B2" or "A1 versus A2 followed by B" and this can be captured on the treatment regimen pages. This page will convey information on more complicated designs, such as "A followed by B versus B followed by A" or "A followed by B versus C followed by D".


Acute myeloid leukemia

COG AAML0531

To be completed

References

  1. Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article PubMed

UK MRC AML12

To be completed

References

  1. Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood. 1999 Jun 15;93(12):4131-43. link to original article PubMed

UK MRC AML15

To be completed

References

  1. Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed

Acute promyelocytic leukemia

C9710

Note: this trial included a second randomization during the maintenance phase, which is not complex and is therefore not reported here.

Arm 1

Arm 2, with ATO3

Comparative efficacy

Regimen Efficacy
Without ATO3 Inferior EFS
With ATO3 Superior EFS

References

  1. Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. link to original article contains dosing details in manuscript link to PMC article PubMed

Breast cancer

DBCG 82b

Arm 1 (Experimental)

Arm 2 (Control)

Comparative efficacy

Regimen Efficacy
With RT Superior OS
Without RT Inferior OS

References

  1. Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med. 1997 Oct 2;337(14):949-55. link to original article PubMed

Loesch et al. 2010

Arm 1, control

Arm 2, experimental

Comparative efficacy

Regimen Efficacy
AC-P Seems not superior
AP-WP Seems not superior

References

  1. Loesch D, Greco FA, Senzer NN, Burris HA, Hainsworth JD, Jones S, Vukelja SJ, Sandbach J, Holmes F, Sedlacek S, Pippen J, Lindquist D, McIntyre K, Blum JL, Modiano MR, Boehm KA, Zhan F, Asmar L, Robert N. Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol. 2010 Jun 20;28(18):2958-65. Epub 2010 May 17. link to original article PubMed

Mavroudis et al. 2017

Arm 1, sequential

Arm 2, concurrent

  • Surgery, then Docetaxel & Epirubicin

Comparative efficacy

Schedule Efficacy
Sequential Might have superior DFS
Concurrent Might have inferior DFS

References

  1. Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Fountzilas G, Rigas G, Varthalitis I, Kalbakis K, Agelaki S, Hatzidaki D, Georgoulias V. Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group. Br J Cancer. 2017 Jul 11;117(2):164-170. Epub 2017 Jun 22. link to original article contains dosing details in manuscript link to PMC article PubMed

NeoALTTO

Arm 1, trastuzumab (C)

Arm 1, lapatinib (E)

Arm 3, lapatinib & trastuzumab (E)

Comparative efficacy

The primary endpoint was pathologic complete response (pCR) rate. Comparison was only between experimental and control arms (i.e., 2 comparisons).

Backbone Efficacy
Trastuzumab vs. Lapatinib Seems not superior
Trastuzumab vs. Lapatinib & Trastuzumab Inferior pCR rate
Lapatinib vs. Trastuzumab Seems not superior
Lapatinib & Trastuzumab vs. Trastuzumab Superior pCR rate

References

  1. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains dosing details in manuscript PubMed
    1. Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed

NOAH

Arm 1, no trastuzumab (Control)

  • AT (Taxol) x 3, then T (Taxol) x 3, then CMF x 3, then surgery

Arm 2, with trastuzumab (Experimental)

Comparative efficacy

Sequencing Efficacy
With trastuzumab Seems to have superior EFS
No trastuzumab Seems to have inferior EFS

References

  1. Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. link to original article PubMed
    1. Update: Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzù D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 May;15(6):640-7. Epub 2014 Mar 20. Erratum in: Lancet Oncol. 2018 Dec;19(12):e667. link to original article PubMed

PREPARE

Arm 1, control

Arm 2, experimental

  • ddE x 3, then ddT (Taxol) x 3, then CMF x 3, then surgery

Comparative efficacy

Regimen Efficacy
Control Seems not superior
Experimental Seems not superior

References

  1. Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Beckmann MW, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Nekljudova V, Lebeau A, Loibl S, Fasching PA; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer--outcome on prognosis. Ann Oncol. 2011 Sep;22(9):1999-2006. Epub 2011 Mar 7. link to original article PubMed

Recht et al. 1996

Arm 1, chemo first

Arm 2, RT first

Comparative efficacy

anti-HER2 medication Comparative Efficacy
Chemo first Seems to have superior MFS
RT first Seems to have inferior MFS

References

  1. Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. link to original article PubMed

SBG 9401

Arm 1 (control)

Arm 2 (experimental)

  • Tailored FEC x 6

Comparative efficacy

Regimen Efficacy
Control Seems to have inferior RFS
Experimental Seems to have superior RFS

References

  1. Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group 9401 study. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. link to original article PubMed

SWOG-8814

Arm 1 (Control)

Arm 2, CAF-T (Experimental)

Arm 3, CAFT (Experimental)

Comparative efficacy

Comparison 1

Design Efficacy
No chemotherapy Might have inferior OS
With chemotherapy Might have superior OS

Comparison 2

Timing Efficacy
Concurrent (CAFT) Might have inferior DFS
Sequential (CAF-T) Might have superior DFS

References

  1. Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. Epub 2009 Dec 10. link to original article link to PMC article PubMed

TRYPHAENA

Arm A

Arm B

Arm C

Comparative efficacy

Note: this was a cardiac safety study; efficacy findings are not reported.

References

  1. Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. link to original article PubMed

Cervical cancer

NOGGO-AGO

Arm 1 (Control)

Arm 2 (Experimental)

  • Surgery, then adjuvant Carboplatin, Ifosfamide, Erythropoietin alfa, then EBRT & Erythropoietin alfa

Comparative efficacy

Regimen Efficacy
No EPO Might have inferior RFS
With EPO Might have superior RFS

References

  1. Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. link to original article PubMed

Colorectal cancer

CAIRO

Arm 1, sequential single agent (Control)

Arm 2, sequential combinations (Experimental)

Comparative efficacy

Approach Efficacy
Sequential single agent Seems not superior
Sequential combinations Seems not superior

References

  1. Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, de Jong RS, Rodenburg CJ, Vreugdenhil G, Loosveld OJ, van Bochove A, Sinnige HA, Creemers GM, Tesselaar ME, Slee PHTJ, Werter MJ, Mol L, Dalesio O, Punt CJ. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007 Jul 14;370(9582):135-142. link to original article PubMed

FFCD 2000-05

Arm 1, sequential (Control)

Arm 2, combination (Experimental)

Comparative efficacy

Approach Efficacy Toxicity
Sequential Seems not superior Less toxic
Combination Seems not superior More toxic

References

  1. Ducreux M, Malka D, Mendiboure J, Etienne PL, Texereau P, Auby D, Rougier P, Gasmi M, Castaing M, Abbas M, Michel P, Gargot D, Azzedine A, Lombard-Bohas C, Geoffroy P, Denis B, Pignon JP, Bedenne L, Bouché O; Fédération Francophone de Cancérologie Digestive (FFCD) 2000–05 Collaborative Group. Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial. Lancet Oncol. 2011 Oct;12(11):1032-44. Epub 2011 Sep 6. link to original article PubMed

Diffuse large B-cell lymphoma

SWOG S8736

Arm 1 - Control

Arm 2 - Experimental

  • CHOP x 3, then RT x 40 to 5500 cGy

Comparative efficacy

Regimen Efficacy
CHOP x 8 Seems to have inferior OS
CHOP x 3, then RT Seems to have superior OS

References

  1. Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. link to original article PubMed

Endometrial cancer

PORTEC-3

Arm 1 - Control

Arm 2 - Experimental

Comparative efficacy

Modality Efficacy
Radiotherapy Seems to have inferior OS1
Chemoradiotherapy Seems to have superior OS1

1Reported efficacy is based on the 2019 update.

References

  1. de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. Epub 2018 Feb 12. link to original article link to PMC article PubMed
    1. Update: de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Gribaudo S, Provencher D, Hanzen C, Kruitwagen RF, Smit VTHBM, Singh N, Do V, Lissoni A, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019 Sep;20(9):1273-1285. Epub 2019 Jul 22. Erratum in: Lancet Oncol. 2019 Sep;20(9):e468. link to original article PubMed

Follicular lymphoma

GALLIUM

Arm 1 - Control

Arm 2 - Experimental

Comparative efficacy

mAb Efficacy Toxicity
Rituximab-chemotherapy Inferior PFS Superior toxicity
Obinutuzumab-chemotherapy Superior PFS (primary endpoint)
PFS36: 80% vs 73%
(HR 0.66, 95% CI 0.51-0.85) 		Inferior toxicity

References

  1. Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix PubMed

Gastroesophageal cancer

POET

Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
Neoadjuvant chemotherapy only Might have inferior OS
Neoadjuvant chemotherapy and chemoradiotherapy Might have superior OS

References

  1. Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. link to original article PubMed

PRODIGE5/ACCORD17

Arm 1 - Control

Arm 2 - Experimental

Comparative efficacy

Regimen Efficacy
CF-based Seems not superior
FOLFOX4-based Seems not superior

References

  1. Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article PubMed

Glioblastoma

AVAglio

Arm 1, control

Arm 2, experimental

  • Surgery, then adjuvant temozolomide, bevacizumab, RT, then temozolomide & bevacizumab maintenance, then bevacizumab maintenance

Comparative efficacy

Regimen Efficacy
Temozolomide alone Inferior PFS
Bevacizumab-containing arm Superior PFS

References

  1. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. link to original article PubMed

EORTC 22981/26981; NCIC-CTG CE.3

Arm 1, control

Arm 2, experimental

Comparative efficacy

Regimen Efficacy
Radiotherapy alone Inferior OS
Temozolomide-containing arm Superior OS

References

  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; EORTC Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. link to original article PubMed

RTOG 0825

Arm 1, control

Arm 2, experimental

  • Surgery, then adjuvant Temozolomide, Bevacizumab, RT, then Temozolomide & Bevacizumab maintenance

Comparative efficacy

Note: although the control regimen had inferior PFS, the effect size did not reach the prespecified improvement target.

Regimen Efficacy
Temozolomide alone Inferior PFS
Bevacizumab-containing arm Superior PFS (co-primary endpoint)

References

  1. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. link to original article link to PMC article PubMed

Head and neck cancer

EORTC 24954

Arm 1, control

Arm 2, experimental

Comparative efficacy

Regimen Efficacy
Sequential RT Seems not superior
Alternating RT Seems not superior

References

  1. Lefebvre JL, Rolland F, Tesselaar M, Bardet E, Leemans CR, Geoffrois L, Hupperets P, Barzan L, de Raucourt D, Chevalier D, Licitra L, Lunghi F, Stupp R, Lacombe D, Bogaerts J, Horiot JC, Bernier J, Vermorken JB; EORTC Head and Neck Cancer Cooperative Group; EORTC Radiation Oncology Group. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009 Feb 4;101(3):142-52. Epub 2009 Jan 27. link to original article link to PMC article PubMed

RTOG 91-11

Arm 1, induction chemotherapy, then radiotherapy (Control)

Arm 2, concurrent chemoradiotherapy (Experimental)

Arm 3, radiotherapy (Experimental)

Comparative efficacy

Efficacy is based on the 2012 update.

Regimen vs. Arm 1 Arm 2 Arm 3
Arm 1 vs. Inferior LFS Seems to have superior LFS
Arm 2 vs. Superior LFS Seems to have superior LFS
Arm 3 vs. Seems to have inferior LFS Seems to have inferior LFS

References

  1. Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. link to original article PubMed
    1. Update: Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. link to original article contains partial protocol link to PMC article PubMed

Classical Hodgkin lymphoma

EORTC-GELA H8-F

Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
MOPP-ABV x 3, then IFRT Superior OS
STNI Inferior OS

References

  1. Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC; GELA. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains dosing details in supplement PubMed

EORTC-GELA H8-U

Arm 1

Arm 2

Arm 3 (control)

Comparative efficacy

Note: the paper describes this as an equivalence study, although the primary endpoint of EFS had p=0.80.

Regimen Efficacy
MOPP-ABV x 4, then IFRT Inconclusive whether equivalent
MOPP-ABV x 4, then STNI Inconclusive whether equivalent
MOPP-ABV x 6, then IFRT Inconclusive whether equivalent

References

  1. Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains dosing details in supplement PubMed

EORTC/LYSA/FIL H10

Note: randomization in this trial occurred before treatment, but took effect after 2 cycles of ABVD, and only if interim PET-CT was negative.

Arm 1

  • Favorable: ABVD x 4
  • Unfavorable: ABVD x 6

Arm 2

Comparative efficacy

Regimen Efficacy
ABVD x 4 Inconclusive whether non-inferior
ABVD x 3, then INRT Inconclusive whether non-inferior

References

  1. Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article PubMed
    1. Update: André MPE, Girinsky T, Federico M, Reman O, Fortpied C, Gotti M, Casasnovas O, Brice P, van der Maazen R, Re A, Edeline V, Fermé C, van Imhoff G, Merli F, Bouabdallah R, Sebban C, Specht L, Stamatoullas A, Delarue R, Fiaccadori V, Bellei M, Raveloarivahy T, Versari A, Hutchings M, Meignan M, Raemaekers J. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2017 Jun 1;35(16):1786-1794. Epub 2017 Mar 14. link to original article PubMed

GHSG HD17

Arm 1 (Control)

Arm 2 (Experimental)

Comparative efficacy

Chemotherapy Efficacy
2+2 -> IFRT Non-inferior PFS
PET-guided therapy Non-inferior PFS

References

  1. Borchmann P, Plütschow A, Kobe C, Greil R, Meissner J, Topp MS, Ostermann H, Dierlamm J, Mohm J, Thiemer J, Sökler M, Kerkhoff A, Ahlborn M, Halbsguth TV, Martin S, Keller U, Balabanov S, Pabst T, Vogelhuber M, Hüttmann A, Wilhelm M, Zijlstra JM, Moccia A, Kuhnert G, Bröckelmann PJ, von Tresckow B, Fuchs M, Klimm B, Rosenwald A, Eich H, Baues C, Marnitz S, Hallek M, Diehl V, Dietlein M, Engert A. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):223-234. link to original article PubMed NCT01356680

NCIC-CTG/ECOG HD.6

Note: this randomization was for patients with unfavorable risk.

Arm 1

Arm 2

Comparative efficacy

Efficacy is based on the 2011 update.

Regimen Efficacy
ABVD x 4 Seems to have superior OS
ABVD x 2, then STNI Seems to have inferior OS

References

  1. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Bezjak A, Wells WA, Burns BF, Winter JN, Horning SJ, Dar AR, Djurfeldt MS, Ding K, Shepherd LE; National Cancer Institute of Canada Clinical Trials Group; ECOG. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005 Jul 20;23(21):4634-42. Epub 2005 Apr 18. link to original article PubMed
    1. Update: Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; ECOG. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. link to original article link to PMC article PubMed

Mantle cell lymphoma

MCL Younger

Arm 1 (Control)

Arm 2 (Experimental)

Comparative efficacy

Regimen Efficacy
SOC Seems to have inferior TTTF
Cytarabine-based Seems to have superior TTTF

References

  1. Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. Epub 2016 Jun 14. link to original article PubMed
    1. Update: Hermine O, Jiang L, Walewski J, Bosly A, Thieblemont C, Szymczyk M, Pott C, Salles G, Feugier P, Hübel K, Haioun C, Casasnovas RO, Schmidt C, Bouabdallah K, Ribrag V, Kanz L, Dürig J, Metzner B, Sibon D, Cheminant M, Burroni B, Klapper W, Hiddemann W, Unterhalt M, Hoster E, Dreyling M; European Mantle Cell Lymphoma Network. High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023 Jan 20;41(3):479-484. Epub 2022 Dec 5. link to original article PubMed

Multiple myeloma

HOVON-50

Arm 1 (Control)

Arm 2 (Experimental)

Comparative efficacy

Regimen Efficacy
SOC Inferior PFS
Thalidomide-based Superior PFS

References

  1. Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. link to original article PubMed
    1. Update: van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. link to original article PubMed

Non-small cell lung cancer

ECOG 3598

Arm 1 (Control)

Arm 2, with thalidomide (Experimental)

  • TPC, then Carboplatin, Paclitaxel, Thalidomide, RT

Comparative efficacy

Regimen Efficacy
Without thalidomide Seems not superior
With thalidomide Seems not superior

References

  1. Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. link to original article link to PMC article PubMed

IUNO

Arm 1, "early" erlotinib

Arm 2, "late" erlotinib

Comparative efficacy

Timing Efficacy
Maintenance erlotinib Did not meet primary endpoint of OS
Second-line erlotinib Did not meet primary endpoint of OS

References

  1. Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. link to original article contains dosing details in manuscript PubMed

RTOG 9410

Arm 1, sequential (control)

Arm 2, concurrent (experimental)

Arm 3, concurrent (experimental)

Comparative efficacy

Schedule Efficacy
Concurrent Seems to have superior OS
Sequential Seems to have inferior OS

References

  1. Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article PubMed

Ovarian cancer

GOG 114

Arm 1 - Control

Arm 2 - Experimental

Comparative efficacy

Regimen Efficacy
Control Seems to have inferior OS
Experimental Seems to have superior OS

References

  1. Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. link to original article PubMed

Pancreatic cancer

GERCOR LAP07

This study had two randomizations; the second only occurred if patients were progression-free after 4 cycles.

Arm 1 - Control

Arm 2 - Experimental

Arm 3 - Experimental

Arm 4 - Experimental

Comparative efficacy

First randomization

Regimen Efficacy
Gemcitabine Might have superior OS
With Erlotinib Might have inferior OS

Second randomization

Modality Efficacy
Chemotherapy Seems not superior
Chemoradiotherapy Seems not superior

References

  1. Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. link to original article PubMed

Rectal cancer

CinClare

Arm 1 (Control)

Capecitabine & RT, then CapeOx x 1, then TME, then CapeOx x 5

Arm 2 (Experimental)

Genotype-dosed CAPIRI & RT, then genotype-dosed CAPIRI x 1, then TME, then CapeOx x 5

Comparative efficacy

Regimen Efficacy
Control Inferior pCR rate
Experimental Superior pCR rate

References

  1. Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. link to original article link to PMC article PubMed NCT02605265

RAPIDO

Arm 1 (Control)

Capecitabine & RT, then TME, then (per hospital policy) CapeOx x 8 or FOLFOX4 x 12

Arm 2 (Experimental)

RT, then CapeOx x 6 or FOLFOX4 x 9, then TME

Comparative efficacy

Regimen Efficacy
RT, then chemo, then TME Seems to have superior DRTF
Chemo-RT, then TME, +/- adjuvant chemo Seems to have inferior DRTF

References

  1. Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. link to original article PubMed
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