EU Approves Keytruda for First-Line Treatment of Metastatic Nonsquamous NSCLC

Pembrolizumab (Keytruda) earned European approval this week, in combination with platinum-based pemetrexed, for the first-line treatment of metastatic nonsquamous non-small cell lung cancer (NSCLC) in adults whose tumors have no EGFR or ALK mutations. This approval marks the first immunotherapy available in Europe for previously untreated patients.

The approval was based on data collected from the KEYNOTE-189 trial that studied the combination treatment in patients with metastatic nonsquamous NSCLC regardless of PD-L1 tumor expression status. The European Union (EU) approval allows for the marketing of the product in all 28 EU member states and Iceland, Lichtenstein, and Norway.

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KEYNOTE-189 is a phase 3, multicenter, randomized, active-controlled, double-blind trial. Patients were randomized to receive pembrolizumab 200 mg, cisplatin or carboplatin, and pemetrexed intravenously every 3 weeks for 4 cycles followed by pembrolizumab 200 mg for up to 24 months and pemetrexed every 3 weeks (n = 410); or placebo, with cisplatin or carboplatin and pemetrexed, intravenously every 3 weeks for 4 cycles followed by pemetrexed every 3 weeks (n = 206).

The primary outcome endpoints were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included overall response rate (ORR) and duration of response (DOR). Researchers found a statistically significant improvement in OS and PFS for patients randomized to the pembrolizumab combination, with a reduction in the risk of death by 51% (hazard ratio [HR] = 4.9 [95%CI, 0.38-0.64]; P<.00001) and a 48% reduction in the risk of progression or death (HR = 0.52 [95% CI, 0.43-0.64]; P<.00001).

In terms of the secondary outcomes, the ORR was 48% (95% CI, 43-53) for patients randomized to the pembrolizumab combination treatment compared with 19% (95% CI, 14-25) for patients randomized to pemetrexed and platinum chemotherapy alone. The median DOR for patients receiving the pembrolizumab combination therapy was 11.2 months (range, 1.1+ to 18.0+), compared with 7.8 months (range, 2.1+ to 16.4+) for patients receiving pemetrexed and platinum chemotherapy alone.

Pembrolizumab is also approved as a monotherapy in Europe for the first-line treatment of metastatic squamous or nonsquamous NSCLC in patients whose tumors have high PD-L1 expression but lack EGFR or ALK mutations.

“This approval is a first in Europe and adds to the rapidly growing role of Keytruda as a foundation for the treatment of lung cancer,” said Roger Perlmutter, MD, president of Merck Research Laboratories in a statement.

“Lung cancer is the leading cause of cancer death in Europe, and we are committed to doing everything in our power to help address it,” said Frank Clyburn, president of Merck Oncology in a statement.