Clinical Efficacy and Safety of Nivolumab in Japanese Patients With Malignant Pleural Mesothelioma: 3-Year Results of the MERIT Study

Our plain-English summary of Clinical Efficacy and Safety of Nivolumab in Japanese Patients With Malignant Pleural Mesothelioma: 3-Year Results of the MERIT Study, by N. Fujimoto, M. Okada, T. Kijima, et al (JTO Clinical and Research Reports, 2021).

The study

• Authors: N. Fujimoto, M. Okada, T. Kijima, K. Aoe, T. Kato, K. Nakagawa, Y. Takeda, T. Hida, K. Kanai, J. Hirano, Y. Ohe
• Journal: JTO Clinical and Research Reports
• Published: 2021;2(3):100135
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: We examined the long-term efficacy and safety of nivolumab, a human monoclonal antibody that inhibits interactions between the programmed cell death protein-1 receptor and its ligands (programmed death-ligand 1 and programmed death-ligand 2), in Japanese patients with malignant pleural mesothelioma (MPM).

Methods: Japanese patients with previously treated MPM (one or two regimens) were enrolled in a single-arm, phase 2 study and received nivolumab intravenously 240 mg every 2 weeks until progressive disease or unacceptable toxicity. The primary end point was the centrally assessed objective response rate. Other end points included overall survival (OS), progression-free survival (PFS), treatment-related adverse events, and patient-reported outcomes (Lung Cancer Symptom Scale for mesothelioma and EuroQOL visual analog scale). Patient enrollment started on June 16, 2016. Here, we report 3-year follow-up data (cutoff date: November 12, 2019).

Results: Thirty-four patients were enrolled. The centrally assessed objective response rate was previously reported (29.4%). The 2- and 3-year OS rates were 35.3% and 23.5%, respectively, and the corresponding PFS rates were 17.0% and 12.7%. Median OS and PFS were 17.3 and 5.9 months, respectively. Eight patients were alive at 3 years of follow-up. Nivolumab was well tolerated and no new safety signals were found. The patient-reported outcomes were maintained without marked deteriorations during the study.

Conclusions: Our results reveal clinically relevant long-term efficacy and safety of nivolumab for the treatment of MPM.

© 2021 The Authors.

In plain English

This article reported 3-year results of MERIT, a single-arm phase 2 trial in Japan. Thirty-four patients with malignant pleural mesothelioma, previously treated with one or two chemotherapy regimens, received nivolumab, an immunotherapy drug, every 2 weeks. The study did not examine asbestos exposure. Ten of 34 patients (29.4%; 95% CI 16.8% to 46.2%) had a partial response. Overall survival was 35.3% (95% CI 19.9% to 51.0%) at 2 years and 23.5% (11.1% to 38.6%) at 3 years; median survival was 17.3 months (11.5 to 26.6). Eight patients were alive at 3 years; median progression-free survival was 5.9 months. Progression-free survival was longer in 7 patients with sarcomatoid or biphasic tumors, pooled, than in 27 with epithelioid tumors. Treatment-related side effects occurred in 26 patients (76.5%), grade 3 to 4 in 11 (32.4%); none appeared after the earlier report. Quality-of-life scores were maintained among patients with available data. The authors concluded nivolumab showed longer-term efficacy and safety as second- or third-line therapy. They named the single-arm design and small numbers as limitations. Ono Pharmaceutical and Bristol-Myers Squibb funded the study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Open-label, single-arm, phase 2 clinical trial (MERIT); this article reports 3-year follow-up data
• Who was studied: 34 Japanese patients (29 male, 5 female) with unresectable malignant pleural mesothelioma resistant or intolerant to one or two previous regimens (platinum and pemetrexed), at 15 centers in Japan. Enrollment began June 16, 2016, and the data cutoff was November 12, 2019.
• Exposure: Treatment with nivolumab 240 mg by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. Asbestos exposure was not studied.
• Main results:
  • All 34 patients: the centrally assessed objective response rate was 29.4% (95% CI 16.8%–46.2%), or 10 of 34 patients. All 10 were partial responses.
  • All patients: 2-year overall survival was 35.3% (95% CI 19.9–51.0) and 3-year overall survival was 23.5% (95% CI 11.1–38.6). Median overall survival was 17.3 months (95% CI 11.5–26.6 months).
  • All patients: 2-year progression-free survival was 17.0% and 3-year progression-free survival was 12.7%. Median progression-free survival was 5.9 months.
  • Eight patients were alive at 3 years of follow-up, including seven at the database lock.
  • PD-L1-positive patients had 2- and 3-year overall survival of 35.0% and 15.0%, with a median of 19.1 months. PD-L1-negative patients had 2- and 3-year overall survival of 33.3% each, with a median of 11.6 months. The authors reported no significant differences in overall or progression-free survival at 2 or 3 years between these groups.
  • Non-epithelioid patients (sarcomatoid or biphasic pooled, 7 patients) had a median overall survival of 26.6 months, 2- and 3-year overall survival of 57.1% and 42.9%, and a median progression-free survival of 18.2 months. Epithelioid patients (27) had a median overall survival of 15.7 months, 2- and 3-year overall survival of 29.6% and 18.5%, and a median progression-free survival of 3.9 months. The hazard ratio for epithelioid versus non-epithelioid was 2.79 for progression-free survival (95% CI 1.03–7.56, p = 0.043) and 2.10 for overall survival (95% CI 0.73–6.11, p = 0.171).
  • The response rate was 37.5% (9 of 24) in patients with one previous treatment and 10.0% (1 of 10) in patients with two previous treatments.
  • Treatment-related adverse events occurred in 26 patients (76.5%), and grade 3 to 4 events in 11 (32.4%). No additional treatment-related adverse events were seen after the March 14, 2018 cutoff, and there were no grade 5 events.
  • Quality of life, measured with the EQ-VAS and the LCSS-Meso symptom burden scale, was maintained over time among patients with available data.
  • In an exploratory comparison, 3-year survivors had a significantly higher proportion of patients with ECOG performance status 0 than nonsurvivors (p = 0.033). There were no other marked differences in patient characteristics.
• The authors' conclusion: The authors concluded that the 3-year follow-up showed longer-term efficacy and safety of nivolumab, with survival beyond 3 years in some patients and a clinical benefit as second- or third-line therapy for malignant pleural mesothelioma.
• Limitations the authors state:
  • Single-arm design and small sample size (34 patients).
  • Subgroups were small and the study was not powered to detect differences among subgroups, which might introduce bias.
  • The authors cautioned against generalizing the results to patients treated in clinical practice and said the findings should be confirmed in larger studies.

Topics

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Pleural Mesothelioma, Monoclonal Antibody, Overall Survival, Progression-Free Survival, Lung Cancer, Mesothelioma.

Related studies

• A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors — T. Shimizu, K. Fukuoka, et al. (2016)
• Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma — K. Nakagawa, T. Kijima, et al. (2021)
• Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings — N. Ueno, S. Banno, et al. (2019)
• Safety of First-Line Nivolumab Plus Ipilimumab in Very Old (≥ 80 Years) Patients With Unresectable Malignant Pleural Mesothelioma: A Retrospective Single-Center Case Series — T. Shimamoto, Y. Morimoto, et al. (2024)
• Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743 — A. Scherpereel, P. Baas, et al. (2026)
• Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials — J.M. Mankor, M.J. Disselhorst, et al. (2020)

Browse more research in JTO Clinical and Research Reports, or return to medical research.