FDA Approves Pembrolizumab Plus Chemotherapy for Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma

The US Food and Drug Administration announced it has approved pembrolizumab (Keytruda, Merck) plus pemetrexed and platinum chemotherapy as a first-line treatment for unresectable advanced or metastatic malignant pleural mesothelioma (MPM).

The efficacy of the combination was evaluated in KEYNOTE-483, a randomized, open-label trial including patients with unresectable advanced or metastatic MPM who had not received prior systemic therapy for advanced or metastatic disease.

Trial investigators randomized patients 1:1 to receive pembrolizumab for up to 2 years in combination with pemetrexed and platinum-based chemotherapy for up to 6 cycles (n=222) or pemetrexed and platinum-based chemotherapy for up to 6 cycles (n=218).

KEYNOTE-483 showed a statistically significant improvement in overall survival (OS), which was the main efficacy outcome measure of the trial, in patients receiving pembrolizumab with chemotherapy (median OS, 17.3 months) compared to those who received chemotherapy alone (median OS, 16.1 months; hazard ratio [HR], 0.79; P=.0162).

The median progression-free survival was 7.1 months (95% CI, 6.9-8.1) in those receiving the combination therapy and 7.1 months (95% CI, 6.8-7.7) in those receiving chemotherapy alone (HR, 0.80 [95% CI: 0.65, 0.99]; P=.0194).

The confirmed overall response rate was 52% (95% CI, 45.5-59.0) in patients receiving pembrolizumab plus chemotherapy, compared to 29% (95% CI, 23.0-35.4) in those receiving chemotherapy alone. The median duration of response was 6.9 months (95% CI: 5.8, 8.3) in those receiving the combination therapy and 6.8 months (95% CI: 5.5, 8.5) in those receiving chemotherapy alone.

The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity for up to 2 years.

“Adverse reactions occurring in patients with MPM were similar to those receiving pembrolizumab with pemetrexed and platinum chemotherapy,” according to FDA officials. The full prescribing information will be posted on Drugs@FDA.

Source: FDA