Randomized Study of Maintenance Pemetrexed Versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901

Arkadiusz Z. Dudek, Xiaofei Wang, Lin Gu, Stephanie Duong, Thomas E. Stinchcombe, Robert Kratzke, Hossein Borghaei, Everett E. Vokes, Hedy L. Kindler

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

BACKGROUND: The role of maintenance therapy for malignant pleural mesothelioma (MPM) is unknown. We performed a randomized phase II trial to determine if continuation of pemetrexed after first-line pemetrexed and platinum would improve progression-free survival (PFS).

PATIENTS AND METHODS: Eligible patients with unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum were randomized 1:1 to observation or continuation of pemetrexed until progression, stratified by number of cycles (< 6 or 6), cis- or carboplatin containing regimen, and histology. Study size was calculated based on the assumption that observation would produce a median PFS of 3 months and pemetrexed would yield median PFS of 6 months.

RESULTS: A total of 72 patients were registered from December 2010 to June 2016. The study closed early after 53 patients were randomized; 49 eligible (22 on the observation arm and 27 on the pemetrexed arm) were included in the analysis. The median PFS was 3 months (95% confidence interval [CI], 2.6-11.9 months) on observation and 3.4 months (95% CI, 2.8-9.8 months) on pemetrexed (hazard ratio [HR], 0.99; 95% CI, 0.51-1.90; P = .9733). The median overall survival (OS) was 11.8 months (95% CI, 9.3-28.7 months) for observation, and 16.3 months (95% CI, 10.5-26.0 months) for pemetrexed (HR, 0.86; 95% CI, 0.44-1.71; P = .6737). Grade 3 or 4 toxicities on the pemetrexed arm included anemia (8%), lymphopenia (8%), neutropenia (4%), and fatigue (4%). A higher baseline level of soluble mesothelin-related peptide was associated with worse PFS (HR, 1.86; 95% CI, 1.00-3.46; P = .049).

CONCLUSION: Maintenance pemetrexed following initial pemetrexed and platinum chemotherapy does not improve PFS in patients with MPM.

Original languageEnglish (US)
Pages (from-to)553-561.e1
JournalClinical Lung Cancer
Volume21
Issue number6
DOIs
StatePublished - Nov 2020

Bibliographical note

Funding Information:
Dr Dudek has received honoraria from Vanquish Oncology, TTC Oncology, IGF Oncology, Squarex, and Martell Diagnostic Laboratories outside the submitted work; and has received grants to institution for his research from Merck , Eli Lilly , and Bristol-Myers Squibb . Dr Stinchcombe reports receiving grants from Genentech /Roche and AstraZeneca ; and personal fees from Regeneron, Takeda, AstraZeneca, Novartis, Genentech/Roche, and G1 Therapeutics outside the submitted work. Dr Vokes received consulting or advisory fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Merck, Novartis, and Regeneron. Dr Borghaei reports personal fees from Millennium, Merck, BMS, Lilly, Genentech, Celgene, Pfizer, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Axiom, PharmaMar, Huya Bio, and Takeda outside the submitted work. Dr Kindler reports grants and personal fees from AstraZeneca , personal fees from Aldeyra Therapuetics, Astellas, Erytech, Five Prime Therapeutics, Ipsen Pharmaceuticals, Kyow, Merck, Boehringer-Ingelheim, Paredox Therapeutics, Bristol-Myers Squibb, MedImmune, Aduro, Bayer, Deciphera, Glaxo Smith Kline, Lilly, Polaris, and Verastem. The remaining authors have stated that they have no conflicts of interest.

Funding Information:
Dr Dudek has received honoraria from Vanquish Oncology, TTC Oncology, IGF Oncology, Squarex, and Martell Diagnostic Laboratories outside the submitted work; and has received grants to institution for his research from Merck, Eli Lilly, and Bristol-Myers Squibb. Dr Stinchcombe reports receiving grants from Genentech/Roche and AstraZeneca; and personal fees from Regeneron, Takeda, AstraZeneca, Novartis, Genentech/Roche, and G1 Therapeutics outside the submitted work. Dr Vokes received consulting or advisory fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Merck, Novartis, and Regeneron. Dr Borghaei reports personal fees from Millennium, Merck, BMS, Lilly, Genentech, Celgene, Pfizer, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Axiom, PharmaMar, Huya Bio, and Takeda outside the submitted work. Dr Kindler reports grants and personal fees from AstraZeneca, personal fees from Aldeyra Therapuetics, Astellas, Erytech, Five Prime Therapeutics, Ipsen Pharmaceuticals, Kyow, Merck, Boehringer-Ingelheim, Paredox Therapeutics, Bristol-Myers Squibb, MedImmune, Aduro, Bayer, Deciphera, Glaxo Smith Kline, Lilly, Polaris, and Verastem. The remaining authors have stated that they have no conflicts of interest.The authors would like to thank James P. Zacny, PhD for assistance in manuscript preparation. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821, U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233253, and UG1CA233327 (https://acknowledgments.alliancefound.org), and the Engdahl Family Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
The authors would like to thank James P. Zacny, PhD for assistance in manuscript preparation. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821, U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233253, and UG1CA233327 (https://acknowledgments.alliancefound.org), and the Engdahl Family Foundation . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2020 The Author(s)

Keywords

  • Continuation pemetrexed
  • Phase II study
  • Progression-free survival
  • Unresectable mesothelioma

PubMed: MeSH publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Journal Article
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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