Pembrolizumab Plus Chemotherapy Approved for Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma
Expert Perspectives · Lyn Brook · 2024-09-19
The FDA has granted approval to pembrolizumab (Keytruda®, Merck) plus pemetrexed and platinum chemotherapy as first-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma (MPM).
Why it matters: “Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum-pemetrexed is a standard treatment,” wrote Quincy Chu, MD, Chair of the Canadian Cancer Trials Group (CCTG) Investigational New Drug Committee, and colleagues, in the KEYNOTE-483 trial (NCT02784171), on which approval was based. “We hypothesized that the addition of pembrolizumab to platinum-pemetrexed would improve overall survival in patients with pleural mesothelioma.”
What they studied: Efficacy was studied in the phase 2/3, open-label trial which enrolled 440 patients with unresectable advanced or metastatic MPM and no prior systemic therapy for advanced/metastatic disease. Patients were randomized 1:1 to receive either pembrolizumab plus pemetrexed and platinum-based chemotherapy or pemetrexed and platinum-based chemotherapy for six cycles, up to two years.
The primary efficacy outcome measured was overall survival with key secondary efficacy outcomes measured: progression-free survival, objective response rate, and duration of response, as assessed by Blinded Independent Central Review (BICR), according to RECIST v1.1 for mesothelioma.
What they found: For patients receiving pembrolizumab plus chemotherapy, a statistically significant improvement in overall survival was observed. The median overall survival for those receiving pembrolizumab plus chemotherapy was 17.3 months compared with those receiving chemotherapy alone at 16.1 months. Progression-free survival was observed at median of 7.1 months in both arms. The confirmed objective response rate was 52% in the pembrolizumab plus chemotherapy arm compared with 29% in the chemotherapy alone arm. The median duration of response was 6.9 months in the pembrolizumab plus chemotherapy arm compared with 6.8 months in the chemotherapy alone arm.
Adverse events: Adverse events experienced by patients with MPM were similar to those receiving pembrolizumab plus pemetrexed and platinum chemotherapy. Refer to the prescribing information for complete details.
Conclusion: “In patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy was tolerable and resulted in a significant improvement in overall survival,” concluded Dr. Chu and colleagues. “This regimen is a new treatment option for previously untreated advanced pleural mesothelioma.”
Instructions: The recommended dosage is 200 mg of pembrolizumab every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity for up to two years.