FDA Approves Lung Cancer Drug Keytruda as Part of First-Line Combination Regimen

Approval expands product labelling

The FDA has given the nod to pembrolizumab (Keytruda, Merck), an anti-programmed death 1 (PD-1) therapy, in combination with pemetrexed (Alimta, Eli Lilly) and carboplatin (pem/carbo), a commonly used chemotherapy regimen, for the first-line treatment of patients with metastatic nonsquamous non–small-cell lung cancer (NSCLC), irrespective of programmed death ligand 1 (PD-L1) expression. This indication was approved based on tumor response rates and progression-free survival. Continued approval for this indication may be contingent on the verification and description of clinical benefit in confirmatory trials.

The FDA’s decision was based on data from the KEYNOTE-021 trial in 123 previously untreated patients with metastatic nonsquamous NSCLC with no epidermal growth factor receptor (EGFR) or ALK genomic tumor aberrations and irrespective of PD-L1 expression. Pembrolizumab plus pem/carbo demonstrated an objective response rate (ORR) that was nearly double the ORR of pem/carbo alone (55% vs. 29%; respectively); all responses were partial responses. Among patients who received pembrolizumab plus pem/carbo, 93% had a duration of response of six months or longer compared with 81% of patients who received pem/carbo alone. In addition, the findings demonstrated a significant improvement in progression-free survival (PFS), with a median PFS of 13.0 months for patients treated with pembrolizumab plus pem/carbo compared with 8.9 months for those receiving pem/carbo alone (hazard ratio, 0.53; P = 0.0205).

Immune-mediated adverse events occurred during treatment with pembrolizumab. These events included pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of these adverse events, pembrolizumab should be withheld or discontinued and corticosteroids administered when appropriate. Pembrolizumab may also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, pembrolizumab may cause fetal harm when administered to a pregnant woman.

Pembrolizumab is the only anti–PD-1 therapy approved in the first-line setting as both monotherapy and combination therapy for appropriate patients with metastatic NSCLC. Pembrolizumab is approved as monotherapy in the first-line setting for patients with metastatic NSCLC whose tumors have high PD-L1 expression, as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. Pembrolizumab as monotherapy is also indicated for the second-line or greater treatment of patients with metastatic NSCLC whose tumors express PD-L1, with disease progression during or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should demonstrate disease progression during FDA-approved therapy for these aberrations before receiving pembrolizumab.

Source: Merck; May 10, 2017.