In a cohort of a Dutch single-center phase II study (PEMMELA) reported in The Lancet Oncology, Douma et al found that pembrolizumab plus lenvatinib was active in patients with pleural mesothelioma whose disease progressed after treatment with nivolumab plus ipilimumab.
In cohort 1 in the trial, pembrolizumab plus lenvatinib was active in patients whose disease progressed on platinum-based chemotherapy.
Study Details
In cohort 2 of the study, 20 patients enrolled at the Netherlands Cancer Institute, Amsterdam, between December 2022 and March 2023 received pembrolizumab at 200 mg every 3 weeks plus lenvatinib at 20 mg daily for up to 2 years or until disease progression or unacceptable toxicity. The primary endpoint was objective response on investigator assessment.
Key Findings
At data cutoff (in September 2024), median follow-up was 11.9 months (interquartile range = 10.8–15.8 months).
Objective response was observed in 12 (60%, 95% confidence interval [CI] = 36%–81%) of 20 patients, with complete response in 1. Median duration of response was 8.6 months (95% CI = 3.1 months to not reached). Disease control rates at 3 and 6 months were 90.0% and 52.6%, respectively. Median progression-free survival was 6.9 months (95% CI = 5.5 months to not reached).
Grade 3 or 4 treatment-related adverse events occurred in 85% of patients, most commonly hypertension (25%, all grade 3), fatigue (20%, all grade 3), and musculoskeletal pain (10%, all grade 3). Grade 4 events consisted of hyponatremia, decreased neutrophils, and respiratory failure in one patient each. Treatment-related serious adverse events were observed in 35% of patients. A total of 45% of patients required at least one dose reduction, and two (10%) discontinued treatment due to toxicity. No treatment-related deaths occurred.
The investigators concluded: “This study met its primary endpoint, showing high clinical activity of pembrolizumab plus lenvatinib, but with substantial toxicity, in patients with pleural mesothelioma who had progressed after first-line nivolumab plus ipilimumab. This drug combination is promising for future studies in pleural mesothelioma.”
Jacobus A. Burgers, MD, PhD, of the Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp and Dohme. For full disclosures of all study authors, visit thelancet.com.
