FDA Expands Keytruda Indication for First-Line Treatment of Non-Small Cell Lung Cancer

The Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) for the first-line treatment of patients with stage 3 non-small cell lung cancer (NSCLC), who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, with a PD-L1 expression level of 1% or more and do not harbor EGFR or ALK aberrations.

The approval was based on the randomized, multicenter, open-label, active-controlled phase III KEYNOTE-042 trial, conducted in 1,274 patients with stage 3 or 4 NSCLC who had not received prior systemic treatment for metastatic NSCLC and whose tumors expressed PD-L1 (TPS ≥1%).

Patients were randomized to receive 200 mg of Keytruda intravenously every three weeks or investigator’s choice of a carboplatin-containing regimen with either Alimta (pemetrexed) or Taxol (paclitaxel).

Overall survival in those with a PD-L1 expression level of 50% or more, 20% or more and the overall population served as the primary endpoint.

The trial demonstrated statistically significant improved overall survival for patients treated with Keytruda compared with chemotherapy in all three populations.

In the overall population, the median overall survival was 16.7 and 12.1 months for the Keytruda and chemotherapy arms, respectively. For those with a PD-L1 expression level of 20% or more, the median overall survival was 17.7 months for the Keytruda arm compared with 13.0 months in the chemotherapy arm; for those with a PD-L1 expression level of 50% or more, the estimated median overall survival was 20 months and 12.2 months, respectively. There were no significant differences in progression-free survival or overall response rate between arms in any population.

The most common side effects associated with Keytruda monotherapy included fatigue, decreased appetite, dyspnea, cough, rash, constipation, diarrhea, nausea, hypothyroidism, pneumonia, pyrexia and weight loss.

The recommended Keytruda dose for NSCLC is 200 mg as an intravenous infusion over 30 minutes every three weeks.