Health Canada has approved the combination of pembrolizumab with chemotherapy for first-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma (MPM). This represents Canada’s first approved pembrolizumab-chemotherapy combination regimen for patients with MPM.
The decision was based on findings from the IND.227/KEYNOTE-483 trial, which revealed statistically significant improvements in overall survival (OS), overall response rate (ORR), and progression-free survival (PFS) for pembrolizumab plus chemotherapy compared with chemotherapy alone.
IND.227/KEYNOTE-483 Overview
The multicenter, randomized, open-label, phase II/III trial investigated the effects of pembrolizumab on MPM and whether it outperforms standard pemetrexed and platinum-based chemotherapy alone.1 The study also assessed side effects and the impact of the pembrolizumab-chemotherapy combination on quality of life.1
Findings
The trial’s final analysis revealed that pembrolizumab in combination with chemotherapy had a significantly longer OS compared with chemotherapy alone (median OS: pembrolizumab-chemotherapy vs. chemotherapy, 17.3 months vs. 16.1 months).2 The pembrolizumab-chemotherapy combination also demonstrated an advantage over chemotherapy monotherapy for the 3-year OS rate (25% vs. 17%).2
The median PFS was the same for the combination treatment and chemotherapy monotherapy (7.1 months); however, pembrolizumab plus chemotherapy yielded a significantly higher ORR compared with chemotherapy monotherapy (52% vs. 29%).3
Adverse events (AEs) related to study treatment of grade 3 or 4 occurred in 27% participants in the pembrolizumab group and in 15% of participants in the chemotherapy-alone group.2 Hospital admissions for serious AEs related to one or more study drugs were reported in 18% of participants in the pembrolizumab group and 6% of participants in the chemotherapy-alone group.2
Key Outcomes and Trial Design
Participants were randomized 1:1 to intravenous chemotherapy (cisplatin [75 mg/m2] or carboplatin [area under the concentration-time curve 5-6 mg/mL per min] with pemetrexed 500 mg/m2, every 3 weeks for up to six cycles), with or without intravenous pembrolizumab 200 mg every 3 weeks (up to 2 years).2
The primary endpoint was OS, which was monitored continuously throughout the study and during follow-up.1 Participants were evaluated at each treatment cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death.1 The secondary outcomes were PFS and objective response rate (ORR).1
References
- 1. https://clinicaltrials.gov/study/NCT02784171
- 2. Chu Q, Perrone F, Greillier L, et al. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10419):2295-2306. doi:10.1016/S0140-6736(23)01613-6
- 3. https://www.merck.ca/en/newsroom/health-canada-approves-kn483/
