Real-world safety of nivolumab in patients with malignant pleural mesothelioma in Japan: post-marketing surveillance study

Our plain-English summary of Real-world safety of nivolumab in patients with malignant pleural mesothelioma in Japan: post-marketing surveillance study, by N. Fujimoto, A. Akamatsu, C. Honda, et al (Japanese Journal of Clinical Oncology, 2024).

The study

• Authors: N. Fujimoto, A. Akamatsu, C. Honda, M. Aoki, Y. Ohe
• Journal: Japanese Journal of Clinical Oncology
• Published: 2024;54(12):1321-1328
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: This post-marketing surveillance (PMS) was conducted to evaluate the incidence of adverse events with nivolumab in patients with unresectable, advanced or recurrent malignant pleural mesothelioma (MPM) that had progressed after first-line chemotherapy and to identify factors that potentially affected its safety in real-world clinical practice.

Methods: Patients who had not received nivolumab previously were registered between November 2018 and February 2021. Nivolumab was given intravenously 240 mg every 2 weeks or 480 mg every 4 weeks. Patients were followed up for 6 months after treatment initiation. Information on patient characteristics, treatment status, and adverse events was collected.

Results: This PMS enrolled 124 patients, involving 48 sites across Japan. At 6 months, nivolumab therapy was ongoing in 35.5% of patients (44/124) and had been discontinued in 64.5% (80/124). The overall incidence of treatment-related adverse events (TRAEs) was 40.3%; the incidence of Grade 3 or higher TRAEs was 12.9%. The pattern of TRAEs based on System Organ Class categories was generally consistent with those seen in the Japanese phase II MERIT study. The most common Grade 3 or higher TRAEs were interstitial lung disease (2.4%), lung disorder, and diarrhea (each 1.6%). The incidence of TRAEs was significantly higher in inpatients or patients who had good PS, high bodyweight, high body mass index, or autoimmune diseases than in those without these characteristics.

Conclusion: The post-marketing incidence of TRAEs with nivolumab in patients with MPM has been evaluated, and no new safety signals were identified compared to the phase II clinical trial in Japan.

© The Author(s) 2024. Published by Oxford University Press.

In plain English

This study recorded side effects of nivolumab in routine Japanese care of malignant pleural mesothelioma that was unresectable, advanced or recurrent and had progressed after first-line chemotherapy. This prospective post-marketing surveillance study followed 124 patients at 48 sites for 6 months each. Side-effect rates did not differ significantly by asbestos exposure history, which 72 (58.1%) had. Side effects for which a link to nivolumab could not be ruled out occurred in 40.3% of patients (50/124), and Grade 3 or higher ones in 12.9% (16/124). Two deaths were counted as treatment-related because their cause was unknown. These side effects were more frequent in inpatients (49.4%, 40/81) than in outpatients (23.3%, 10/43). They were also more frequent in patients with good performance status, higher body weight or body mass index, or autoimmune disease. The authors cautioned that the autoimmune group had only five patients and that the significant subgroup findings were difficult to interpret clinically. They concluded that no new safety signals were found compared with the earlier 34-patient MERIT trial. They noted there was no control group and follow-up lasted only 6 months.

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: Prospective post-marketing surveillance study (drug safety monitoring in routine clinical practice), with 6 months of observation per patient
• Who was studied: 124 patients in Japan with unresectable, advanced or recurrent malignant pleural mesothelioma (MPM) that had progressed after first-line chemotherapy and who had not received nivolumab before. They were registered at 48 sites between 1 November 2018 and 28 February 2021. Median age was 71.0 years and 83.9% were male. 58.1% (72/124) had a history of asbestos exposure, 25.8% (32/124) did not, and for 16.1% (20/124) it was not known. Median exposure duration was 20.5 years (range 0 to 50) among those with a history.
• Exposure: The drug nivolumab, given intravenously at 240 mg every 2 weeks and/or 480 mg every 4 weeks. Asbestos exposure history was recorded only as a background factor; it was not the exposure under study.
• Main results:
  • Treatment-related adverse events (TRAEs, events where a causal relationship to nivolumab could not be denied) occurred in 40.3% of all patients (50/124).
  • Grade 3 or higher TRAEs occurred in 12.9% of all patients (16/124).
  • The most common Grade 3 or higher TRAEs were interstitial lung disease in 2.4% (3/124), and lung disorder, diarrhea and death in 1.6% each (2/124). The two deaths were regarded as treatment-related because their cause was unknown.
  • TRAEs in the category 'respiratory, thoracic, and mediastinal disorders' were more frequent in this surveillance (9.7%; 12/124) than in the MERIT trial (5.9%; 2/34).
  • TRAEs were statistically significantly more frequent in inpatients (49.4%, 40/81) than in outpatients (23.3%, 10/43), P = 0.007. They were also more frequent in patients with performance status 0 to 1 (43.9%, 50/114) than in those with 2 to 4 (0%, 0/10), P = 0.007.
  • TRAEs were also more frequent with higher body weight (P = 0.024) and higher body mass index (P = 0.050). They occurred in 100% (5/5) of patients with a history of autoimmune disease versus 37.8% (45/119) of those without, P = 0.009.
  • No significant difference in TRAE incidence was seen between subgroups by asbestos exposure history (or by sex, age and other listed background factors).
  • At 6 months, nivolumab had been stopped in 64.5% of patients (80/124). Stopping because of an adverse event accounted for 21.8% (27/124).
  • During the 6-month observation period, 25 of the 124 patients (20.2%) died from any cause.
• The authors' conclusion: The authors concluded that the post-marketing incidence of TRAEs with nivolumab in MPM had been evaluated and that no new safety signals were identified compared with the Japanese phase II MERIT trial.
• Limitations the authors state:
  • There was no control group, and follow-up was limited to 6 months.
  • Efficacy data were not collected.
  • The small size of the MERIT trial (34 patients) limits comparison of event rates with it.
  • The group with poorer performance status (2 or above) was small, so the absence of TRAEs in that group calls for caution.
  • The autoimmune disease subgroup was too small (5 patients) to draw conclusions about a link with TRAEs.
  • The authors found it difficult to give a clear clinical interpretation for all the factors that showed a significantly higher incidence of TRAEs.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Pleural Mesothelioma, Unresectable, Chemotherapy, Interstitial Lung Disease, Clinical Trial.

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