Clinical Outcomes Associated With Pembrolizumab Immunotherapy in Mesothelioma: A Systematic Review
Author(s)
Nallamothu Bhargavi, Ph.D.1, Kapil Maheshchandra KHAMBHOLJA, Ph.D.2, VATSAL AKHILESH CHHAYA, M.S.2, Arpit Shah, Ph.D.2.
1Medical Writing, Catalyst Clinical Research, Trivandrum, India, 2Medical Writing, Catalyst Clinical Research, Vadodara, India.
1Medical Writing, Catalyst Clinical Research, Trivandrum, India, 2Medical Writing, Catalyst Clinical Research, Vadodara, India.
OBJECTIVES: To summarize current evidence on pembrolizumab in mesothelioma, focusing on efficacy, safety, and predictive biomarkers across subtypes and treatment settings.
METHODS: A systematic review was conducted using PubMed and ClinicalTrials.gov to identify studies on pembrolizumab in mesothelioma (Jan 2015-May 2025). Included were clinical trials, observational studies, and real-world reports assessing efficacy, safety, and biomarkers in pleural and peritoneal mesothelioma across treatment lines. Outcomes included ORR, PFS, OS, adverse events, and biomarker associations. Non-English publications, reviews, and non-pembrolizumab studies were excluded
RESULTS: Of 94 records screened, 25 studies met inclusion. In first-line malignant pleural mesothelioma (MPM), the KEYNOTE-483 trial showed pembrolizumab plus pemetrexed-platinum improved OS (17.3 vs. 16.1 months; HR=0.79, p=0.0162), ORR (52% vs. 29%), and 1- and 2-year PFS. Benefits were seen across PD-L1 levels and more so in non-epithelioid histology. FDA approval followed in Sept 2024, despite higher grade 3-4 toxicity (27% vs. 15%). In second-line MPM, early-phase and real-world studies showed ORRs of 18-21% and OS up to 20.9 months, especially in PD-L1 ≥50% or non-epithelioid subtypes. PROMISE-meso showed no PFS advantage over chemotherapy. Investigational strategies (DREAM3R, BEAT-meso, neoadjuvant use, CAR T-cell combinations) are ongoing. PD-L1, TMB, and MSI-H lacked consistent predictive value; histology remains the most reliable marker. Immune-related AEs require close monitoring in patients with limited pulmonary reserve.
CONCLUSIONS: Pembrolizumab shows benefit in mesothelioma, particularly first-line MPM in combination with chemotherapy per KEYNOTE-483. Monotherapy may help select second-line patients with non-epithelioid disease. Biomarker performance remains limited; histology is most predictive. In peritoneal mesothelioma, early efficacy signals warrant further study.
METHODS: A systematic review was conducted using PubMed and ClinicalTrials.gov to identify studies on pembrolizumab in mesothelioma (Jan 2015-May 2025). Included were clinical trials, observational studies, and real-world reports assessing efficacy, safety, and biomarkers in pleural and peritoneal mesothelioma across treatment lines. Outcomes included ORR, PFS, OS, adverse events, and biomarker associations. Non-English publications, reviews, and non-pembrolizumab studies were excluded
RESULTS: Of 94 records screened, 25 studies met inclusion. In first-line malignant pleural mesothelioma (MPM), the KEYNOTE-483 trial showed pembrolizumab plus pemetrexed-platinum improved OS (17.3 vs. 16.1 months; HR=0.79, p=0.0162), ORR (52% vs. 29%), and 1- and 2-year PFS. Benefits were seen across PD-L1 levels and more so in non-epithelioid histology. FDA approval followed in Sept 2024, despite higher grade 3-4 toxicity (27% vs. 15%). In second-line MPM, early-phase and real-world studies showed ORRs of 18-21% and OS up to 20.9 months, especially in PD-L1 ≥50% or non-epithelioid subtypes. PROMISE-meso showed no PFS advantage over chemotherapy. Investigational strategies (DREAM3R, BEAT-meso, neoadjuvant use, CAR T-cell combinations) are ongoing. PD-L1, TMB, and MSI-H lacked consistent predictive value; histology remains the most reliable marker. Immune-related AEs require close monitoring in patients with limited pulmonary reserve.
CONCLUSIONS: Pembrolizumab shows benefit in mesothelioma, particularly first-line MPM in combination with chemotherapy per KEYNOTE-483. Monotherapy may help select second-line patients with non-epithelioid disease. Biomarker performance remains limited; histology is most predictive. In peritoneal mesothelioma, early efficacy signals warrant further study.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO48
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Oncology