Pembrolizumab and Chemotherapy Receive FDA Approval for First-Line Treatment of Pleural Mesothelioma

On 17 September 2024, the United States Food and Drug Administration (FDA) approved the combination of the immunotherapy pembrolizumab (Keytruda, Merck) with pemetrexed and platinum-based chemotherapy as first-line treatment for unresectable advanced or metastatic malignant pleural mesothelioma (MPM).

Pleural mesotheliomais an aggressive cancer affecting the lining of the lungs and is usually associated with asbestos exposure. About 3,000 people in the United States and about 500 in Türkiye are diagnosed with mesothelioma each year. Although there is still no curative treatment for mesothelioma, which is often diagnosed at an advanced stage, innovations in chemotherapy, targeted therapies, immunotherapies and electrotherapy are producing promising results.

FDA Approval Based on the KEYNOTE-483 Study

KEYNOTE-483 was a phase 3, multicenter, open-label study of patients with previously untreated advanced pleural mesothelioma who were not eligible for surgery. Of the 440 participants, 218 received chemotherapy alone and 222 received chemotherapy with pembrolizumab.

Findings

According to the study results:

• Median overall survival among patients receiving chemotherapy with pembrolizumab was 17.3 months, compared with 16.1 months (HR 0.79; 95% CI 0.64–0.98, p=0·0324) with chemotherapy alone.
• The two-year overall survival rate was 39% and the three-year rate was 25% among patients treated with the addition of pembrolizumab, compared with 33% and 17%, respectively, with chemotherapy alone.
• Median progression-free survival was 7.1 months in the pembrolizumab treatment group and 7.1 months in the chemotherapy-only group. However, the risk of progression was lower among those treated with pembrolizumab (HR: 0.80; p=0.0194).
• The confirmed objective response rate was 52% in the pembrolizumab group and 29% in the chemotherapy-only group.

Treatment-related adverse events of any grade were frequent in both groups: 98% versus 95%. The most common were fatigue and nausea. Diarrhea, skin effects and myelosuppression were more common among patients receiving pembrolizumab. Grade 3-4 (serious) adverse events occurred in 27% of patients receiving pembrolizumab and 15% of those receiving chemotherapy alone.

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