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".


Acute promyelocytic leukemia

C9710

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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 verified protocol link to PMC article PubMed

Breast cancer

ABCSG-8

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ABCSG-8: Austrian Breast and Colorectal Cancer Study Group 8

Arm 1, monotherapy (Control)

Arm 2, sequential (Experimental)

Comparative efficacy

Regimen Efficacy
Tamoxifen Might have inferior RFS
Tamoxifen, then Anastrozole Might have superior RFS

References

  1. Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. link to original article PubMed

ACOSOG Z1041

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Arm 1 - Control

Arm 2 - Experimental

Comparative efficacy

Approach Efficacy
Sequential trastuzumab (C) Seems not superior
Concurrent trastuzumab (E) Seems not superior

References

  1. Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig G, Royce M, McCall LM, Ewer MS, Hunt KK; American College of Surgeons Oncology Group investigators. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1317-25. Epub 2013 Nov 13. link to original article link to PMC article PubMed

ARNO 95

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Arm 1, monotherapy (Control)

Arm 2, sequential (Experimental)

Comparative efficacy

Regimen Efficacy
Tamoxifen, then Anastrozole Seems to have superior OS
Tamoxifen Seems to have inferior OS

References

  1. Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. link to original article PubMed

Assikis et al. 2003

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
FAC, then MV Seems not superior
Tamoxifen Seems not superior

References

  1. Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. link to original article contains protocol PubMed

BCIRG-005

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Arm 1, sequential

Arm 2, concurrent

Comparative efficacy

Schedule Efficacy
Sequential (AC, then T) Seems not superior
Concurrent (TAC) Seems not superior

References

  1. 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. link to original article contains verified protocol PubMed

BCIRG 006

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Arm 1, sequential without trastuzumab

Arm 2, sequential with trastuzumab

Arm 3, concurrent with trastuzumab

Comparative efficacy

  • Analyzed using a step-down design

Comparison 1

Trastuzumab-containing regimens vs. AC, then T Efficacy
AC, then TH Superior OS
TCH Seems to have superior OS

Comparison 2

Trastuzumab-containing regimens Efficacy
AC, then TH Seems not superior
TCH Seems not superior

References

  1. 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. link to original article link to PMC article PubMed

BIG 1-98

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Arm 1, monotherapy

Arm 2, sequential

Arm 3, monotherapy

Arm 4, sequential

Comparative efficacy

  • Analyzed by several methods; efficacy here is based on the 2011 update.

Comparison 1

Monotherapy Efficacy
Letrozole Superior OS
Tamoxifen Inferior OS

Comparison 2

Sequential therapies Efficacy
Letrozole, then Tamoxifen Seems not superior
Tamoxifen, then Letrozole Seems not superior

Comparison 3

Letrozole-containing therapies Efficacy
Letrozole Seems not superior
Letrozole, then Tamoxifen Seems not superior
Tamoxifen, then Letrozole Seems not superior

References

  1. Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. link to original article PubMed
    1. Update: Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. link to original article PubMed
    2. Subgroup analysis: Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. link to original article PubMed
    3. Subgroup analysis: Crivellari D, Sun Z, Coates AS, Price KN, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens RJ, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Gladieff L, Rabaglio M, Smith IE, Chirgwin JH, Goldhirsch A. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008 Apr 20;26(12):1972-9. Epub 2008 Mar 10. link to original article PubMed
    4. Update: Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG 1-98 Collaborative Group.; International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. link to original article link to PMC article PubMed

BR9601

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
CMF x 8 Inferior OS
EC x 4, then CMF x 4 Superior OS

References

  1. Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. link to original article contains verified protocol PubMed

Buzdar et al. 2005

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Arm 1

  • Neoadjuvant T, then FEC

Arm 2

Comparative efficacy

Regimen Efficacy
T, then FEC Seems to have inferior pCR rate
TH, then FEC & H Seems to have superior pCR rate

References

  1. Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. link to original article PubMed

CALGB 9741

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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

  • A, then T, then C

Arm 2, dose-dense sequential

Arm 3, "concurrent"

Arm 4, dose-dense "concurrent"

Comparative efficacy

  • Analyzed using a 2 x 2 factorial design

Comparison 1

Dose density Efficacy
Dose-dense (q2wk) Seems to have superior OS
Standard (q3wk) Seems to have inferior OS

Comparison 2

Schedule Efficacy
Concurrent Seems not superior
Sequential Seems not superior

References

  1. 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. link to original article contains verified protocol PubMed

DBCG 07-READ

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Arm 1

Arm 2, "EC-D"

  • EC x 3, then D x 3

Comparative efficacy

Regimen Efficacy
DC x 6 Seems not superior
EC x 3, then D x 3 Seems not superior

References

  1. Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. link to original article contains verified protocol PubMed

DEVA

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Arm 1 (Control)

Arm 2 (Experimental)

Comparative efficacy

Regimen Efficacy
Epirubicin Inferior DFS
Epirubicin, then Docetaxel Superior DFS

References

  1. Coombes RC, Bliss JM, Espie M, Erdkamp F, Wals J, Tres A, Marty M, Coleman RE, Tubiana-Mathieu N, den Boer MO, Wardley A, Kilburn LS, Cooper D, Thomas MW, Reise JA, Wilkinson K, Hupperets P. Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer. J Clin Oncol. 2011 Aug 20;29(24):3247-54. Epub 2011 Jul 18. link to original article PubMed

FinXX

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Arm 1 (Control)

Arm 2 (Experimental)

  • TX x 3, then CEX x 3

Comparative efficacy

Regimen Efficacy
T x 3, then CEF x 3 Might have inferior RFS
TX x 3, then CEX x 3 Might have superior RFS

References

  1. Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtiö K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, Leinonen M, Lindman H; FinXX Study Investigators. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol. 2009 Dec;10(12):1145-51. Epub 2009 Nov 10. link to SD article PubMed
    1. Update: Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol. 2012 Jan 1;30(1):11-8. Epub 2011 Nov 21. link to original article PubMed

FNCLCC PACS 01

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
FEC x 6 Seems to have inferior OS
FEC x 3, then D x 3 Seems to have superior OS

References

  1. Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 Dec 20;24(36):5664-71. Epub 2006 Nov 20. link to original article PubMed

GEICAM 9906

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
FEC x 6 Inferior DFS
FEC x 4, then T Superior DFS

References

  1. 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. link to original article PubMed

GeparQuinto

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Arm 1 - Control

Arm 2 - Experimental

Comparative efficacy

Note that while this study met the primary efficacy endpoint, the advantage for bevacizumab was only seen in the triple-negative breast cancer patients, with p=0.003 in this subgroup.

Regimen Efficacy
No bevacizumab Seems to have inferior pCR rate
With bevacizumab Seems to have superior pCR rate

References

  1. von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article PubMed

HannaH

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Arm 1, IV trastuzumab

Arm 2, SC trastuzumab

Comparative efficacy

Route of administration Efficacy
IV trastuzumab Non-inferior pCR rate
SC trastuzumab Non-inferior pCR rate

References

  1. Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. Epub 2012 Aug 9. link to original article contains verified protocol PubMed

HORG CT/07.17

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
ddFEC → D Inconclusive whether non-inferior
TC Inconclusive whether non-inferior

References

  1. Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG), Athens, Greece. Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. link to original article PubMed

IES

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IES: Intergroup Exemestane Study

Arm 1, monotherapy (Control)

Arm 2, sequential (Experimental)

Comparative efficacy

Note: reported efficacy is based on the 2011 update.

Regimen Efficacy
Tamoxifen x 5y Seems to have inferior OS
Tamoxifen x 2-3y, then Exemestane x 2-3y (5y total) Seems to have superior OS

References

  1. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. link to original article PubMed
    1. Update: Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. link to original article PubMed
    2. Update: Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC. Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J Clin Oncol. 2012 Mar 1;30(7):709-17. Epub 2011 Oct 31. link to original article PubMed

Mavroudis et al. 2017

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Arm 1, sequential

Arm 2, concurrent

  • 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 articlecontains verified protocol PubMed

NCCTG N9831

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Arm 1, no trastuzumab

Arm 2, sequential trastuzumab

Arm 3, concurrent trastuzumab

Comparative efficacy

Comparison 1

Note: Arm 2 was not included in this joint analysis. Efficacy is based on the 2014 update.

Regimen Efficacy
AC, then T Inferior OS
AC, then TH Superior OS

Comparison 2

Note: efficacy is as reported in the 2011 update.

Trastuzumab-containing regimens Efficacy
AC, then T, then H Might have inferior DFS
AC, then TH Might have superior DFS

References

  1. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. link to original article PubMed
    1. Update: Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. link to original article link to PMC article PubMed
    2. Update: Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. link to original article link to PMC article PubMed

NEAT

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
CMF x 6 Inferior OS
EC x 4, then CMF x 4 Superior OS

References

  1. Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. link to original article contains verified protocol PubMed

NeoALTTO

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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 verified protocol 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

NSABP B-38

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Arm 1, sequential without gemcitabine

Arm 1, sequential with gemcitabine

Arm 3, concurrent

Comparative efficacy

Schedule Efficacy
Sequential (ddAC, then ddP) Seems not superior
Sequential (ddAC, then ddPG) Seems not superior
Concurrent (TAC) Seems not superior

References

  1. Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. link to original article link to PMC article contains verified protocol PubMed

NSABP B-40

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Arm 1 - Control

Arm 2

Arm 3

  • TX x 4, then AC x 4, then surgery

Arm 4

Arm 5

  • TG x 4, then AC x 4, then surgery

Arm 6

Comparative efficacy

This trial was analyzed using a 3 x 2 factorial design; primary endpoint was pathologic complete response (pCR) rate.

Addition of bevacizumab

Regimen Efficacy
No bevacizumab (C) Seems to have inferior pCR rate
Bevacizumab-based therapy (E) Seems to have superior pCR rate

Addition of capecitabine or gemcitabine

Regimen Efficacy
Docetaxel alone (C) Seems not superior
TX or TG (E) Seems not superior

References

  1. Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
    1. Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed

TACT2

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Arm 1

Arm 2

Arm 3

Arm 4

Comparative efficacy

  • Analyzed using a 2 x 2 factorial design

Comparison 1

Dose density of epirubicin Efficacy
Dose-dense (q2wk) Seems not superior
Standard (q3wk) Seems not superior

Comparison 2

Capecitabine vs. CMF Efficacy
Capecitabine Non-inferior TTR
CMF Non-inferior TTR

References

  1. Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. link to original article link to PMC article contains verified protocol PubMed

TEAM

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Arm 1, monotherapy

Arm 2, sequential

Comparative efficacy

Regimen Efficacy
Tamoxifen x 5y Seems not superior
Tamoxifen x 2.5-3y, then Exemestane x 2-2.5y Seems not superior

References

  1. van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. link to original article contains verified protocol PubMed
    1. Update: Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. 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

Gastroesophageal cancer

FLOT4-AIO

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Arm 1 - Control

Arm 2 - Experimental

Comparative efficacy

Regimen Efficacy
ECF/ECX Seems to have inferior OS
FLOT Seems to have superior OS

References

  1. Abstract: Salah-Eddin Al-Batran, Nils Homann, Harald Schmalenberg, Hans-Georg Kopp, Georg Martin Haag, Kim Barbara Luley, Wolff H. Schmiegel, Gunnar Folprecht, Stephan Probst, Nicole Prasnikar, Peter C. Thuss-Patience, Wolfgang Fischbach, Jorg Trojan, Michael Koenigsmann, Claudia Pauligk, Thorsten Oliver Goetze, Elke Jaeger, Johannes Meiler, Martin H. Schuler, and Ralf Hofheinz. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. Journal of Clinical Oncology 2017 35:15_suppl, 4004-4004 link to abstract

MAGIC

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Arm 1 - Control

Arm 2 - Experimental

  • ECF x 3, then surgery, then ECF x 3

Comparative efficacy

Regimen Efficacy
Surgery alone Inferior OS
Perioperative ECF Superior OS

References

  1. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article PubMed

POET

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Arm 1

  • PLF x 15 wk, then surgery

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

Glioblastoma

EORTC 22981/26981; NCIC CTG CE.3

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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; European Organisation for Research and Treatment of Cancer 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

Hodgkin lymphoma

EORTC 20012

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
BEACOPP4+4 Seems not superior
ABVD x 8 Seems not superior

References

  1. Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, Caillot D, Gaillard I, Bologna S, Ferme C, Lugtenburg PJ, Morschhauser F, Aurer I, Coiffier B, Meyer R, Seftel M, Wolf M, Glimelius B, Sureda A, Mounier N. Eight cycles of ABVD versus four cycles of BEACOPPescalated plus four cycles of BEACOPPbaseline in stage III to IV, International Prognostic Score ≥ 3, high-risk Hodgkin lymphoma: First results of the phase III EORTC 20012 Intergroup trial. J Clin Oncol. 2016 Jun 10;34(17):2028-36. Epub 2016 Apr 25. link to original article contains verified protocol PubMed

EORTC-GELA H8-F

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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 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 verified protocol in supplement PubMed

EORTC-GELA H8-U

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Arm 1

Arm 2

Arm 3

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 verified protocol in supplement PubMed

EORTC/LYSA/FIL H10

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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

GHSG HD11

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Note: the primary endpoints of this trial, which were to determine the superiority of BEACOPP vs. ABVD and noninferiority of 20 Gy vs. 30 Gy of IFRT, were not reported in the manuscript.

Arm 1

Arm 2

Arm 3

Arm 4

Comparative efficacy

  • Designed using a 2 x 2 factorial design

Comparison 1

Chemotherapy Efficacy
ABVD Not reported
BEACOPP Not reported

Comparison 2

Radiotherapy Efficacy
IFRT x 20 Gy Not reported
IFRT x 30 Gy Not reported

References

  1. Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, Ho A, Dörken B, Rank A, Grosu AL, Wiegel T, Karstens JH, Greil R, Willich N, Schmidberger H, Döhner H, Borchmann P, Müller-Hermelink HK, Müller RP, Engert A. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20;28(27):4199-206. Epub 2010 Aug 16. link to original article PubMed

GHSG HD12

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Arm 1

Arm 2

Arm 3

Arm 4

Comparative efficacy

  • Designed using a 2 x 2 factorial design

Comparison 1

Chemotherapy Efficacy
BEACOPPescalated x 8 Non-inferior 5-year FFTF
BEACOPPescalated x 4, then BEACOPP x 4 Non-inferior 5-year FFTF

Comparison 2

Radiotherapy Efficacy
ISRT x 30 Gy Might have superior 5-year FFTF
No radiotherapy Might have inferior 5-year FFTF

References

  1. Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed

GHSG HD14

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Arm 1

Arm 2

Comparative efficacy

Chemotherapy Efficacy
ABVD x 4 Inferior FFTF
eBEACOPP x 2, then ABVD x 2 Superior FFTF

References

  1. von Tresckow B, Plütschow A, Fuchs M, Klimm B, Markova J, Lohri A, Kral Z, Greil R, Topp MS, Meissner J, Zijlstra JM, Soekler M, Stein H, Eich HT, Mueller RP, Diehl V, Borchmann P, Engert A. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20;30(9):907-13. Epub 2012 Jan 23. link to original article PubMed

LYSA H34

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
BEACOPP4+4 Might have superior EFS
ABVD x 8 Might have inferior EFS

References

  1. Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed

NCIC CTG/ECOG HD.6

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Note: this randomization was for patients with unfavorable risk.

Arm 1

Arm 2

Comparative efficacy

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, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. 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

Viviani et al. 2011 (IIL)

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Arm 1

Arm 2

Comparative efficacy

Regimen Efficacy
BEACOPP4+4 Seems to have superior FFFP
ABVD x 8 Seems to have inferior FFFP

References

  1. Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article PubMed

Non-small cell lung cancer

ECOG 3598

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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

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Arm 1, "early" erlotinib

Arm 2, "late" erlotinib

Comparative efficacy

Timing Efficacy
Maintenance erlotinib Seems not superior
Second-line erlotinib Seems not superior

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 verified protocol PubMed

RTOG 9410

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Arm 1, sequential

Arm 2, concurrent

Arm 3, concurrent

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

OCEANS

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Arm 1 - Control

Arm 2 - Experimental

Comparative efficacy

Regimen Efficacy
Carbo-Gem Inferior PFS
With Bevacizumab Superior PFS

References

  1. Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. Epub 2012 Apr 23. link to original article link to PMC article PubMed

Pancreatic cancer

GERCOR LAP07

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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
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