Difference between revisions of "Malignant pleural mesothelioma"
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**'''2009:''' Stahel et al. [https://doi.org/10.1093/annonc/mdp134 Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454470/ PubMed] | **'''2009:''' Stahel et al. [https://doi.org/10.1093/annonc/mdp134 Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454470/ PubMed] | ||
**'''2008:''' Stahel et al. [https://doi.org/10.1093/annonc/mdn083 Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456764/ PubMed] | **'''2008:''' Stahel et al. [https://doi.org/10.1093/annonc/mdn083 Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456764/ PubMed] | ||
− | == | + | ==NCCN== |
*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1512 NCCN Guidelines - Mesothelioma: Pleural] | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1512 NCCN Guidelines - Mesothelioma: Pleural] | ||
**'''2016:''' Ettinger et al. [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc10187059/ NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016] [https://pubmed.ncbi.nlm.nih.gov/27407123/ PubMed] | **'''2016:''' Ettinger et al. [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc10187059/ NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016] [https://pubmed.ncbi.nlm.nih.gov/27407123/ PubMed] |
Revision as of 11:23, 13 May 2024
Section editor | |
---|---|
Marjorie G. Zauderer, MD, MS, FACP Memorial Sloan Kettering Cancer Center New York, NY, USA |
Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
19 regimens on this page
32 variants on this page
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Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO
- 2018: Kindler et al. Treatment of malignant pleural mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline PubMed
ESMO
- 2021: Popat et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2015: Baas et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
- 2010: Stahel et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Stahel et al. Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Stahel et al. Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
NCCN
- NCCN Guidelines - Mesothelioma: Pleural
- 2016: Ettinger et al. NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016 PubMed
- 2012: Ettinger et al. Malignant pleural mesothelioma. PubMed
SITC
- 2022: Govindan et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma PubMed
Advanced or metastatic disease, first-line therapy
Carboplatin & Pemetrexed
Regimen variant #1, AUC 5/500 x 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Castagneto et al. 2007 | 2003-07 to 2005-03 | Phase 2 | ||
Baas et al. 2021 (CheckMate 743) | 2016-2018 | Phase 3 (C) | Ipilimumab & Nivolumab | Inferior OS1 |
Chu et al. 2023 (IND227) | 2017-01-31 to 2020-09-04 | Phase 3 (C) | 1a. Carboplatin, Pemetrexed, Pembrolizumab 1b. Cisplatin, Pemetrexed, Pembrolizumab |
Seems to have inferior OS |
1Reported efficacy for CheckMate 743 is based on the 2022 update.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second, 30 minutes after pemetrexed
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
Supportive therapy
- (varies depending on reference):
- Folic acid 350 to 600 mcg PO once per day, starting at least 1 week prior to pemetrexed, to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week prior to pemetrexed, then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) by one of the following:
- 4 mg PO twice per day the day before, the day of, and day after pemetrexed
- 8 mg IM once the day before, the day of, and day after pemetrexed
- No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after pemetrexed
21-day cycle for 6 cycles
Regimen variant #2, AUC 5/500 x 9
Study | Dates of enrollment | Evidence |
---|---|---|
Castagneto et al. 2007 | 2003-07 to 2005-03 | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second, 30 minutes after pemetrexed
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
Supportive therapy
- (varies depending on reference):
- Folic acid 350 to 600 mcg PO once per day, starting at least 1 week prior to pemetrexed, to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week prior to pemetrexed, then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
- Alternatively, Dexamethasone (Decadron) may be given 8 mg IM the day before, the day of, and day after pemetrexed
- No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after pemetrexed
21-day cycle for up to 9 cycles
Regimen variant #3, AUC 5/500, indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Ceresoli et al. 2006 | 2002-11 to 2005-03 | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second, 30 minutes after pemetrexed
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
Supportive therapy
- (varies depending on reference):
- Folic acid 350 to 600 mcg PO once per day, starting at least 1 week prior to pemetrexed, to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week prior to pemetrexed, then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
- Alternatively, Dexamethasone (Decadron) may be given 8 mg IM the day before, the day of, and day after pemetrexed
- No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after pemetrexed
21-day cycles
Regimen variant #4, AUC 6/500 x 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chu et al. 2023 (IND227) | 2017-01-31 to 2020-09-04 | Phase 3 (C) | 1a. Carboplatin, Pemetrexed, Pembrolizumab 1b. Cisplatin, Pemetrexed, Pembrolizumab |
Seems to have inferior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Supportive therapy
- (varies depending on reference):
- Folic acid 350 to 600 mcg PO once per day, starting at least 1 week prior to pemetrexed, to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once at least 1 week prior to pemetrexed, then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
- Alternatively, Dexamethasone (Decadron) may be given 8 mg IM the day before, the day of, and day after pemetrexed
- No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days (5 days for NSAIDs with longer half-lives) before or after pemetrexed
21-day cycle for 6 cycles
References
- Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, Ceribelli A, Bearz A, Morenghi E, Cavina R, Marangolo M, Parra HJ, Santoro A. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006 Mar 20;24(9):1443-8. link to original article contains dosing details in manuscript PubMed
- Castagneto B, Botta M, Aitini E, Spigno F, Degiovanni D, Alabiso O, Serra M, Muzio A, Carbone R, Buosi R, Galbusera V, Piccolini E, Giaretto L, Rebella L, Mencoboni M. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann Oncol. 2008 Feb;19(2):370-3. Epub 2007 Dec 20. link to original article contains dosing details in manuscript PubMed
- CheckMate 743: Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Jahan T, Antonia S, Oulkhouir Y, Bautista Y, Cornelissen R, Greillier L, Grossi F, Kowalski D, Rodríguez-Cid J, Aanur P, Oukessou A, Baudelet C, Zalcman G. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. Epub 2021 Jan 21. link to original article contains dosing details in abstract PubMed NCT02899299
- Update: Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, Talbot T, Monnet I, Hiret S, Baas P, Nowak AK, Fujimoto N, Tsao AS, Mansfield AS, Popat S, Zhang X, Hu N, Balli D, Spires T, Zalcman G. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022 May;33(5):488-499. Epub 2022 Feb 3. link to original article PubMed
- IND227: Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. Epub 2023 Nov 3. link to original article contains dosing details in manuscript PubMed NCT02784171
Carboplatin, Pemetrexed, Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (BEAT-meso) | 2019-ongoing | Phase 3 (C) | ABCP | TBD if different primary endpoint of OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4 up to 6: AUC 5 IV once on day 1
- Pemetrexed (Alimta) as follows:
- Cycles 1 to 4 up to 6: 500 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- BEAT-meso: NCT03762018
Carboplatin, Pemetrexed, Pembrolizumab
Regimen variant #1, AUC 5
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chu et al. 2023 (IND227) | 2017-01-31 to 2020-09-04 | Phase 3 (E-esc) | 1a. Carboplatin & Pemetrexed 1b. Cisplatin & Pemetrexed |
Seems to have superior OS (primary endpoint) Median OS: 17.3 vs 16.1 mo (HR 0.79, 95% CI 0.64-0.98) |
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV once on day 1
- Pemetrexed (Alimta) as follows:
- Cycles 1 to 6: 500 mg/m2 IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
Regimen variant #2, AUC 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chu et al. 2023 (IND227) | 2017-01-31 to 2020-09-04 | Phase 3 (E-esc) | 1a. Carboplatin & Pemetrexed 1b. Cisplatin & Pemetrexed |
Seems to have superior OS (primary endpoint) Median OS: 17.3 vs 16.1 mo (HR 0.79, 95% CI 0.64-0.98) |
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 IV once on day 1
- Pemetrexed (Alimta) as follows:
- Cycles 1 to 6: 500 mg/m2 IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- IND227: Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. Epub 2023 Nov 3. link to original article contains dosing details in manuscript PubMed NCT02784171
Cisplatin monotherapy
Regimen variant #1, 75 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vogelzang et al. 2003 (EMPHACIS) | 1999-2001 | Phase 3 (C) | Cisplatin & Pemetrexed | Seems to have inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Regimen variant #2, 80 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van Meerbeeck et al. 2005 (EORTC 08983) | 2000-2003 | Phase 3 (C) | Cisplatin & Raltitrexed | Seems to have inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
References
- EMPHACIS: Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. link to original article contains dosing details in manuscript PubMed NCT00005636
- Update: Manegold C, Symanowski J, Gatzemeier U, Reck M, von Pawel J, Kortsik C, Nackaerts K, Lianes P, Vogelzang NJ. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Ann Oncol. 2005 Jun;16(6):923-7. Epub 2005 Apr 11. link to original article PubMed
- EORTC 08983: van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G; EORTC Lung Cancer Group; National Cancer Institute of Canada Clinical Trials Group. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005 Oct 1;23(28):6881-9. link to original article contains dosing details in manuscript PubMed NCT00004920
Cisplatin & Gemcitabine (GC)
Regimen variant #1, 100/1000
Study | Evidence |
---|---|
Nowak et al. 2002 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 1, given first
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, given second
Supportive therapy
- Minimum of 3 liters of IV hydration for [cisplatin, with magnesium supplementation
- 5-HT3 antagonists & Dexamethasone (Decadron) IV once per day on days 1, 8, 15, prior to chemotherapy
- 5-HT3 antagonists, Dexamethasone (Decadron), and/or phenothiazines for antiemesis PO or by rectal suppository for 3 to 5 days after cisplatin
28-day cycle for up to 6 cycles
Regimen variant #2, 80/1250
Study | Evidence |
---|---|
van Haarst et al. 2002 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 3 hours once on day 1, given second
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
Supportive therapy
- Minimum of 2 liters of IV hydration for cisplatin
- 5-HT3 antagonists prior to cisplatin
- corticosteroids prior to cisplatin
21-day cycle for up to 6 cycles
References
- van Haarst JM, Baas P, Manegold Ch, Schouwink JH, Burgers JA, de Bruin HG, Mooi WJ, van Klaveren RJ, de Jonge MJ, van Meerbeeck JP. Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma. Br J Cancer. 2002 Feb 1;86(3):342-5. link to original article contains dosing details in manuscript link to PMC article PubMed content property of HemOnc.org
- Nowak AK, Byrne MJ, Williamson R, Ryan G, Segal A, Fielding D, Mitchell P, Musk AW, Robinson BW. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma. Br J Cancer. 2002 Aug 27;87(5):491-6. link to original article contains dosing details in manuscript link to PMC article PubMed
Cisplatin & Pemetrexed
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vogelzang et al. 2003 (EMPHACIS) | 1999-2001 | Phase 3 (E-RT-esc) | Cisplatin | Seems to have superior OS (primary endpoint) Median OS: 12.1 vs 9.3 mo (HR 0.77) |
Zalcman et al. 2016 (MAPS) | 2008-2014 | Phase 3 (C) | PCB | Seems to have inferior OS |
Grosso et al. 2017 (LUME-Meso) | 2013-09 to 2014-12 | Phase 2/3 (C) | Cisplatin, Nintedanib, Pemetrexed | Did not meet primary endpoint of PFS1 |
Baas et al. 2021 (CheckMate 743) | 2016-2018 | Phase 3 (C) | Ipilimumab & Nivolumab | Inferior OS2 |
Chu et al. 2023 (IND227) | 2017-01-31 to 2020-09-04 | Phase 3 (C) | 1a. Carboplatin, Pemetrexed, Pembrolizumab 1b. Cisplatin, Pemetrexed, Pembrolizumab |
Seems to have inferior OS |
Awaiting publication (DREAM3R) | 2021-ongoing | Phase 3 (C) | 1a. Carboplatin, Pemetrexed, Durvalumab 1b. Cisplatin, Pemetrexed, Durvalumab |
TBD if different primary endpoint of OS |
1Reported efficacy for LUME-Meso is based on the 2019 update.
2Reported efficacy for CheckMate 743 is based on the 2022 update.
Note: EMPHACIS (aka JMCH) did not specify the total number of cycles and some patients did receive more than 6 cycles.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 2 hours once on day 1, given second, 30 minutes after pemetrexed
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
Supportive therapy
- Folic acid 350 to 1000 mcg PO once per day, starting 1 to 3 weeks prior to pemetrexed, to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 3 weeks prior to pemetrexed, then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) (dose not specified by reference) the day before, the day of, and day after pemetrexed
21-day cycle for up to 6 cycles (see note)
References
- EMPHACIS: Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. link to original article contains dosing details in manuscript PubMed NCT00005636
- Update: Manegold C, Symanowski J, Gatzemeier U, Reck M, von Pawel J, Kortsik C, Nackaerts K, Lianes P, Vogelzang NJ. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Ann Oncol. 2005 Jun;16(6):923-7. Epub 2005 Apr 11. link to original article PubMed
- MAPS: Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, Rivière F, Janicot H, Gervais R, Locher C, Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Parienti JJ, Scherpereel A; IFCT. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2;387(10026):1405-14. Epub 2015 Dec 21. Erratum in: Lancet. 2016 Apr 2;387(10026):e24. link to original article contains dosing details in abstract PubMed NCT00651456
- LUME-Meso: Grosso F, Steele N, Novello S, Nowak AK, Popat S, Greillier L, John T, Leighl NB, Reck M, Taylor P, Planchard D, Sørensen JB, Socinski MA, von Wangenheim U, Loembé AB, Barrueco J, Morsli N, Scagliotti G. Nintedanib plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma: Phase II results from the randomized, placebo-controlled LUME-Meso trial. J Clin Oncol. 2017 Nov 1;35(31):3591-3600. Epub 2017 Sep 11. link to original article contains dosing details in manuscript PubMed NCT01907100
- Update: Scagliotti GV, Gaafar R, Nowak AK, Nakano T, van Meerbeeck J, Popat S, Vogelzang NJ, Grosso F, Aboelhassan R, Jakopovic M, Ceresoli GL, Taylor P, Orlandi F, Fennell DA, Novello S, Scherpereel A, Kuribayashi K, Cedres S, Sørensen JB, Pavlakis N, Reck M, Velema D, von Wangenheim U, Kim M, Barrueco J, Tsao AS. Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2019 Jul;7(7):569-580. Epub 2019 May 15. link to original article PubMed
- CheckMate 743: Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Jahan T, Antonia S, Oulkhouir Y, Bautista Y, Cornelissen R, Greillier L, Grossi F, Kowalski D, Rodríguez-Cid J, Aanur P, Oukessou A, Baudelet C, Zalcman G. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. Epub 2021 Jan 21. link to original article contains dosing details in abstract PubMed NCT02899299
- Update: Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, Talbot T, Monnet I, Hiret S, Baas P, Nowak AK, Fujimoto N, Tsao AS, Mansfield AS, Popat S, Zhang X, Hu N, Balli D, Spires T, Zalcman G. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022 May;33(5):488-499. Epub 2022 Feb 3. link to original article PubMed
- IND227: Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. Epub 2023 Nov 3. link to original article contains dosing details in manuscript PubMed NCT02784171
- DREAM3R: NCT04334759
Cisplatin & Raltitrexed
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van Meerbeeck et al. 2005 (EORTC 08983) | 2000-2003 | Phase 3 (E-esc) | Cisplatin | Seems to have superior OS (primary endpoint) Median OS: 11.4 vs 8.8 mo (HR 0.76, 95% CI 0.58-1.00) |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 1 to 2 hours once on day 1, given second
- Raltitrexed (Tomudex) 3 mg/m2 IV over 15 minutes once on day 1, given first
21-day cycles
References
- EORTC 08983: van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, Legrand C, Bottomley A, Debruyne C, Giaccone G; EORTC Lung Cancer Group; National Cancer Institute of Canada Clinical Trials Group. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005 Oct 1;23(28):6881-9. link to original article contains dosing details in manuscript PubMed NCT00004920
Cisplatin, Pemetrexed, Bevacizumab
PCB: Pemetrexed, Cisplatin, Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zalcman et al. 2016 (MAPS) | 2008-2014 | Phase 3 (E-esc) | PC | Superior OS (primary endpoint) Median OS: 18.8 vs 16.1 mo (HR 0.77, 95% CI 0.62-0.95) |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 6 cycles
References
- MAPS: Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, Rivière F, Janicot H, Gervais R, Locher C, Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Parienti JJ, Scherpereel A; IFCT. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2;387(10026):1405-14. Epub 2015 Dec 21. Erratum in: Lancet. 2016 Apr 2;387(10026):e24. link to original article contains dosing details in abstract PubMed NCT00651456
Cisplatin, Pemetrexed, Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chu et al. 2023 (IND227) | 2017-01-31 to 2020-09-04 | Phase 3 (E-esc) | 1a. Carboplatin & Pemetrexed 1b. Cisplatin & Pemetrexed |
Seems to have superior OS (primary endpoint) Median OS: 17.3 vs 16.1 mo (HR 0.79, 95% CI 0.64-0.98) |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 6: 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) as follows:
- Cycles 1 to 6: 500 mg/m2 IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- IND227: Chu Q, Perrone F, Greillier L, Tu W, Piccirillo MC, Grosso F, Lo Russo G, Florescu M, Mencoboni M, Morabito A, Cecere FL, Ceresoli GL, Dawe DE, Zucali PA, Pagano M, Goffin JR, Sanchez ML, Gridelli C, Zalcman G, Quantin X, Westeel V, Gargiulo P, Delfanti S, Tu D, Lee CW, Leighl N, Sederias J, Brown-Walker P, Luo Y, Lantuejoul S, Tsao MS, Scherpereel A, Bradbury P, Laurie SA, Seymour L. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023 Dec 16;402(10419):2295-2306. Epub 2023 Nov 3. link to original article contains dosing details in manuscript PubMed NCT02784171
Cisplatin, Pemetrexed, TTFields
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Ceresoli et al. 2019 (STELLAR) | 2015-2017 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
Tumor treating fields
References
- STELLAR: Ceresoli GL, Aerts JG, Dziadziuszko R, Ramlau R, Cedres S, van Meerbeeck JP, Mencoboni M, Planchard D, Chella A, Crinò L, Krzakowski M, Rüssel J, Maconi A, Gianoncelli L, Grosso F. Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1702-1709. Epub 2019 Oct 15. link to original article PubMed NCT02397928
Ipilimumab & Nivolumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baas et al. 2021 (CheckMate 743) | 2016-2018 | Phase 3 (E-RT-switch-ooc) | 1a. Carboplatin & Pemetrexed 1b. Cisplatin & Pemetrexed |
Superior OS1 (primary endpoint) Median OS: 18.1 vs 14.1 mo (HR 0.73, 95% CI 0.61-0.87) |
1Reported efficacy is based on the 2022 update.
Immunotherapy
- Ipilimumab (Yervoy) 1 mg/kg IV once on day 1
- Nivolumab (Opdivo) 3 mg/kg IV once per day on days 1, 15, 29
42-day cycle for up to 18 cycles (2 years)
References
- CheckMate 743: Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Jahan T, Antonia S, Oulkhouir Y, Bautista Y, Cornelissen R, Greillier L, Grossi F, Kowalski D, Rodríguez-Cid J, Aanur P, Oukessou A, Baudelet C, Zalcman G. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. Epub 2021 Jan 21. link to original article contains dosing details in abstract PubMed NCT02899299
- Update: Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, Talbot T, Monnet I, Hiret S, Baas P, Nowak AK, Fujimoto N, Tsao AS, Mansfield AS, Popat S, Zhang X, Hu N, Balli D, Spires T, Zalcman G. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022 May;33(5):488-499. Epub 2022 Feb 3. link to original article PubMed
Pemetrexed monotherapy
Regimen
Study | Evidence |
---|---|
Taylor et al. 2008 | Phase 2 |
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
Supportive therapy
- Folic acid 350 to 600 mcg PO once per day, starting 1 to 2 weeks before pemetrexed, to continue throughout therapy and at least 3 weeks after the last dose of pemetrexed
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 2 weeks prior to pemetrexed, then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
21-day cycles
References
- Taylor P, Castagneto B, Dark G, Marangolo M, Scagliotti GV, van Klaveren RJ, Labianca R, Serke M, Schuette W, van Meerbeeck JP, Heigener D, Liu Y, Adachi S, Blatter J, von Pawel J. Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. J Thorac Oncol. 2008 Jul;3(7):764-71. link to original article contains dosing details in manuscript PubMed
Vinorelbine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Muers et al. 2008 (MS01) | 2001-2006 | Phase 3 (E-esc) | 1. Best supportive care | Might have superior OS (primary endpoint) Median OS: 9.5 vs 7.6 mo (HR 0.80, 95% CI 0.63-1.02) |
2. MVP | Not directly compared |
Note: Some guidelines list the dosage as 25 to 30 mg/m2. No primary reference could be found for the 25 mg/m2 dosage. Note also that it is not clear from the reference whether 11 or 12 doses were given.
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
7-week cycle for 2 cycles
References
- MS01: Muers MF, Stephens RJ, Fisher P, Darlison L, Higgs CM, Lowry E, Nicholson AG, O'Brien M, Peake M, Rudd R, Snee M, Steele J, Girling DJ, Nankivell M, Pugh C, Parmar MK; MS01 Trial Management Group. Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet. 2008 May 17;371(9625):1685-94. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00075699
Advanced or metastatic disease, subsequent lines of therapy
Doxorubicin monotherapy
Regimen variant #1, 60 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gregorc et al. 2018 (NGR015) | 2010-2013 | Phase 3 (C) | Investigator's choice of: 1a. Doxorubicin & NGR-hTNF 1b. Gemcitabine & NGR-hTNF 1c. Vinorelbine & NGR-hTNF |
Did not meet primary endpoint of OS Median OS: 8 vs 8.5 mo (HR 1.06, 95% CI 0.85-1.33) |
Note: this is the lower bound of dosing used in NGR015. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Prior treatment criteria
- NGR015: One prior pemetrexed-containing regimen
Regimen variant #2, 75 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gregorc et al. 2018 (NGR015) | 2010-2013 | Phase 3 (C) | Investigator's choice of: 1a. Doxorubicin & NGR-hTNF 1b. Gemcitabine & NGR-hTNF 1c. Vinorelbine & NGR-hTNF |
Did not meet primary endpoint of OS Median OS: 8 vs 8.5 mo (HR 1.06, 95% CI 0.85-1.33) |
Note: this is the upper bound of dosing used in NGR015. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Prior treatment criteria
- NGR015: One prior pemetrexed-containing regimen
References
- NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article contains dosing details in abstract PubMed NCT01098266
Gemcitabine monotherapy
Regimen variant #1, 1000 mg/m2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gregorc et al. 2018 (NGR015) | 2010-2013 | Phase 3 (C) | Investigator's choice of: 1a. Doxorubicin & NGR-hTNF 1b. Gemcitabine & NGR-hTNF 1c. Vinorelbine & NGR-hTNF |
Did not meet primary endpoint of OS Median OS: 8 vs 8.5 mo (HR 1.06, 95% CI 0.85-1.33) |
Popat et al. 2020 (PROMISE-meso) | 2017-09 to 2018-08 | Phase 3 (C) | Pembrolizumab | Did not meet primary endpoint of PFS |
Note: this is the lower bound of dosing used in NGR015. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Prior treatment criteria
- NGR015: One prior pemetrexed-containing regimen
- PROMISE-meso: Failure of platinum-based chemotherapy
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #2, 1000 mg/m2, 3 out of 4 weeks
Study | Evidence |
---|---|
Zauderer et al. 2014meso | Retrospective, fewer than 20 pts |
Regimen variant #3, 1250 mg/m2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gregorc et al. 2018 (NGR015) | 2010-2013 | Phase 3 (C) | Investigator's choice of: 1a. Doxorubicin & NGR-hTNF 1b. Gemcitabine & NGR-hTNF 1c. Vinorelbine & NGR-hTNF |
Did not meet primary endpoint of OS Median OS: 8 vs 8.5 mo (HR 1.06, 95% CI 0.85-1.33) |
Note: this is the upper bound of dosing used in NGR015. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Prior treatment criteria
- NGR015: One prior pemetrexed-containing regimen
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
References
- Retrospective: Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer. 2014 Jun;84(3):271-4. Epub 2014 Mar 14. link to original article contains dosing details in abstract link to PMC article PubMed
- NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article contains dosing details in abstract PubMed NCT01098266
- PROMISE-meso: Popat S, Curioni-Fontecedro A, Dafni U, Shah R, O'Brien M, Pope A, Fisher P, Spicer J, Roy A, Gilligan D, Gautschi O, Nadal E, Janthur WD, López Castro R, García Campelo R, Rusakiewicz S, Letovanec I, Polydoropoulou V, Roschitzki-Voser H, Ruepp B, Gasca-Ruchti A, Peters S, Stahel RA. A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Ann Oncol. 2020 Dec;31(12):1734-1745. Epub 2020 Sep 22. link to original article contains dosing details in manuscript PubMed NCT02991482
Gemcitabine & Vinorelbine
Regimen
Study | Evidence |
---|---|
Zauderer et al. 2014meso | Retrospective, fewer than 20 pts |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Retrospective: Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer. 2014 Jun;84(3):271-4. Epub 2014 Mar 14. link to original article contains dosing details in abstract link to PMC article PubMed
Nivolumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fennell et al. 2021 (CONFIRMmeso) | 2017-2020 | Phase 3 (E-esc) | Placebo | Superior OS (co-primary endpoint) Median OS: 10.2 vs 6.9 mo (HR 0.69, 95% CI 0.52-0.91) |
Note: this trial should not be confused with the one by the same name in breast cancer.
Prior treatment criteria
- Failure of first-line platinum-based chemotherapy
Immunotherapy
- Nivolumab (Opdivo) 240 mg IV over 30 minutes once on day 1
14-day cycle for up to 26 cycles (1 year)
References
- CONFIRMmeso: Fennell DA, Ewings S, Ottensmeier C, Califano R, Hanna GG, Hill K, Danson S, Steele N, Nye M, Johnson L, Lord J, Middleton C, Szlosarek P, Chan S, Gaba A, Darlison L, Wells-Jordan P, Richards C, Poile C, Lester JF, Griffiths G; CONFIRM trial investigators. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol. 2021 Nov;22(11):1530-1540. Epub 2021 Oct 14. link to original article contains dosing details in abstract link to PMC article PubMed NCT03063450
Pemetrexed monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jassem et al. 2008 (JMEW) | 2001-2004 | Phase 3 (E-esc) | Best supportive care | Did not meet primary endpoint of OS Median OS: 9.7 vs 8.4 mo |
Prior treatment criteria
- One prior systemic chemotherapy regimen, not including pemetrexed
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
Supportive therapy
- Folic acid 350 to 1000 mcg PO once per day, starting 1 to 2 weeks prior to pemetrexed, to continue throughout therapy and at least 3 weeks after the last dose of pemetrexed
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once 1 to 2 weeks prior to pemetrexed, then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
21-day cycle for 8 or more cycles
References
- JMEW: Jassem J, Ramlau R, Santoro A, Schuette W, Chemaissani A, Hong S, Blatter J, Adachi S, Hanauske A, Manegold C. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol. 2008 Apr 1;26(10):1698-704. link to original article contains dosing details in manuscript PubMed NCT00190762
Vinorelbine monotherapy
Regimen variant #1, 25 mg/m2 IV, 2 weeks out of 3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gregorc et al. 2018 (NGR015) | 2010-2013 | Phase 3 (C) | Investigator's choice of: 1a. Doxorubicin & NGR-hTNF 1b. Gemcitabine & NGR-hTNF 1c. Vinorelbine & NGR-hTNF |
Did not meet primary endpoint of OS Median OS: 8 vs 8.5 mo (HR 1.06, 95% CI 0.85-1.33) |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Prior treatment criteria
- NGR015: One prior pemetrexed-containing regimen
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #2, 25 mg/m2 IV, weekly
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gregorc et al. 2018 (NGR015) | 2010-2013 | Phase 3 (C) | Investigator's choice of: 1a. Doxorubicin & NGR-hTNF 1b. Gemcitabine & NGR-hTNF 1c. Vinorelbine & NGR-hTNF |
Did not meet primary endpoint of OS Median OS: 8 vs 8.5 mo (HR 1.06, 95% CI 0.85-1.33) |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Prior treatment criteria
- NGR015: One prior pemetrexed-containing regimen
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Regimen variant #3, 30 mg/m2 IV, 2 weeks out of 3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Popat et al. 2020 (PROMISE-meso) | 2017-09 to 2018-08 | Phase 3 (C) | Pembrolizumab | Did not meet primary endpoint of PFS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Prior treatment criteria
- PROMISE-meso: Failure of platinum-based chemotherapy
Regimen variant #4, 30 mg/m2 IV, weekly
Study | Evidence |
---|---|
Stebbing et al. 2008 | Phase 2 |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 (maximum dose of 60 mg) IV over 5 minutes once per day on days 1, 8, 15, 22, 29, 36
42-day cycles
Regimen variant #5, 60 mg/m2 PO, 2 weeks out of 3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gregorc et al. 2018 (NGR015) | 2010-2013 | Phase 3 (C) | Investigator's choice of: 1a. Doxorubicin & NGR-hTNF 1b. Gemcitabine & NGR-hTNF 1c. Vinorelbine & NGR-hTNF |
Did not meet primary endpoint of OS Median OS: 8 vs 8.5 mo (HR 1.06, 95% CI 0.85-1.33) |
Popat et al. 2020 (PROMISE-meso) | 2017-09 to 2018-08 | Phase 3 (C) | Pembrolizumab | Did not meet primary endpoint of PFS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Prior treatment criteria
- NGR015: One prior pemetrexed-containing regimen
- PROMISE-meso: Failure of platinum-based chemotherapy
Regimen variant #6, 60 mg/m2 PO, weekly
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gregorc et al. 2018 (NGR015) | 2010-2013 | Phase 3 (C) | Investigator's choice of: 1a. Doxorubicin & NGR-hTNF 1b. Gemcitabine & NGR-hTNF 1c. Vinorelbine & NGR-hTNF |
Did not meet primary endpoint of OS Median OS: 8 vs 8.5 mo (HR 1.06, 95% CI 0.85-1.33) |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Prior treatment criteria
- NGR015: One prior pemetrexed-containing regimen
Chemotherapy
- Vinorelbine (Navelbine) 60 mg/m2 PO once per day on days 1, 8, 15
21-day cycle for 4 cycles
Regimen variant #7, 80 mg/m2 PO, 2 weeks out of 3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Popat et al. 2020 (PROMISE-meso) | 2017-09 to 2018-08 | Phase 3 (C) | Pembrolizumab | Did not meet primary endpoint of PFS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Prior treatment criteria
- PROMISE-meso: Failure of platinum-based chemotherapy
References
- Stebbing J, Powles T, McPherson K, Shamash J, Wells P, Sheaff MT, Slater S, Rudd RM, Fennell D, Steele JP. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer. 2009 Jan;63(1):94-7. Epub 2008 May 16. link to original article contains dosing details in manuscript PubMed
- NGR015: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, Bidoli P, Tiseo M, Shah R, Taylor P, Novello S, Muzio A, Bearz A, Greillier L, Fontana F, Salini G, Lambiase A, O'Brien M. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018 Jun;19(6):799-811. Epub 2018 May 9. link to original article contains dosing details in abstract PubMed NCT01098266
- PROMISE-meso: Popat S, Curioni-Fontecedro A, Dafni U, Shah R, O'Brien M, Pope A, Fisher P, Spicer J, Roy A, Gilligan D, Gautschi O, Nadal E, Janthur WD, López Castro R, García Campelo R, Rusakiewicz S, Letovanec I, Polydoropoulou V, Roschitzki-Voser H, Ruepp B, Gasca-Ruchti A, Peters S, Stahel RA. A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Ann Oncol. 2020 Dec;31(12):1734-1745. Epub 2020 Sep 22. link to original article contains dosing details in manuscript PubMed NCT02991482