Tumor response rate and progression-free survival (PFS) were the benchmarks that helped pembrolizumab (Keytruda) gain accelerated approval as first-line treatment for metastatic nonsquamous non-small cell lung cancer (NSCLC), in combination with pemetrexed (pem) and carboplatin (carbo), irrespective of PD-L1 expression.
Observations in a subpopulation of patients who were part of the KEYNOTE-021 trial led to the new approval. A cohort of 123 treatment-naïve patients with metastatic nonsquamous NSCLC, with no mutations in EGFR
genes, were treated with pembrolizumab plus pem/carbo or pem/carbo alone. Including pembrolizumab in the treatment regimen improved the objective response rate from 29% (95% CI: 18-41) to 55% (95% CI: 42-68). Further, a majority of patients (93%) who received pembrolizumab had a duration of response that was at least 6 months (range, 1.4+ to 13+ months), compared with 81% of patients who did not (range, 1.4+ to 15.2+ months). Pembrolizumab also improved the median PFS by about 3.1 months.
With respect to adverse events, pembrolizumab treatment resulted in pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Pembrolizumab can also cause severe or life-threatening infusion-related reactions.
“This approval marks an important milestone in the treatment of lung cancer. Now, pembrolizumab in combination with pemetrexed and carboplatin can be prescribed in the first-line setting for patients with metastatic nonsquamous non-small cell lung cancer, irrespective of PD-L1 expression,” said
Corey Langer, MD, director of thoracic oncology and professor of medicine at the Hospital of the University of Pennsylvania. Langer emphasized that physicians should consider individual patient characteristics, such as biomarker status, histology, and other clinical factors, to carve out an appropriate treatment plan.
The approval of pembrolizumab as first-line therapy, alone
or in combination with chemotherapy agents, has opened up the horizon’s for Merck, the company that has developed the molecule. More than 200,000 individuals are diagnosed annually
with NSCLC in the United States.
The drug spend will be an issue—the combination of pembrolizumab and chemotherapy will cost
more than $250,000 annually.