Malignant pleural mesothelioma - null regimens

The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the main mesothelioma page for current regimens.

Advanced or metastatic disease, first-line therapy

Best supportive care

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Muers et al. 2008 (MS01)	2001-2006	Phase III (C)	1. MVP	Did not meet primary endpoint of OS
			2. Vinorelbine	Might have inferior OS

No antineoplastic treatment; used as a comparator arm and here for reference purposes only.

References

1. 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 verified protocol link to PMC article PubMed ISRCTN54469112

Maintenance after first line therapy

Best supportive care

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Buikhuisen et al. 2013 (NVALT 5)	2004-2009	Phase III (C)	Thalidomide	Did not meet primary endpoint of TTP

No antineoplastic treatment after first-line therapy.

Preceding treatment

• Pemetrexed-containing chemotherapy x 4

References

1. NVALT 5: Buikhuisen WA, Burgers JA, Vincent AD, Korse CM, van Klaveren RJ, Schramel FM, Pavlakis N, Nowak AK, Custers FL, Schouwink JH, Gans SJ, Groen HJ, Strankinga WF, Baas P. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study. Lancet Oncol. 2013 May;14(6):543-51. Epub 2013 Apr 12. link to original article PubMed ISRCTN13632914

Advanced or metastatic disease, subsequent lines of therapy

Best supportive care

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Jassem et al. 2008 (JMEW)	2001-2004	Phase III (C)	Pemetrexed	Seems to have inferior PFS
Maio et al. 2017 (DETERMINE)	2013-2014	Randomized Phase IIb (C)	Tremelimumab	Did not meet primary endpoint of OS

No antineoplastic treatment.

References

1. 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 verified protocol PubMed NCT00190762
2. DETERMINE: Maio M, Scherpereel A, Calabrò L, Aerts J, Cedres Perez S, Bearz A, Nackaerts K, Fennell DA, Kowalski D, Tsao AS, Taylor P, Grosso F, Antonia SJ, Nowak AK, Taboada M, Puglisi M, Stockman PK, Kindler HL. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017 Sep;18(9):1261-1273. Epub 2017 Jul 17. link to original article PubMed NCT01843374

Placebo

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Krug et al. 2015 (VANTAGE-014)	2005-2011	Phase III (C)	Vorinostat	Did not meet primary endpoint of OS
Fennell et al. 2021 (CONFIRMmeso)	2017-2020	Phase III (C)	Nivolumab	Inferior OS

No active antineoplastic treatment. Note that CONFIRM should not be confused with the trial by the same name in breast cancer.

References

1. VANTAGE-014: Krug LM, Kindler HL, Calvert H, Manegold C, Tsao AS, Fennell D, Öhman R, Plummer R, Eberhardt WE, Fukuoka K, Gaafar RM, Lafitte JJ, Hillerdal G, Chu Q, Buikhuisen WA, Lubiniecki GM, Sun X, Smith M, Baas P. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2015 Apr;16(4):447-56. Epub 2015 Mar 20. Erratum in: Lancet Oncol. 2015 May;16(5):e199. link to original article PubMed NCT00128102
2. CONFIRM_meso: 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 protocol link to PMC article PubMed NCT03063450