Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer

Area of Science:

• Oncology
• Immunotherapy
• Pharmacology

Background:

• Advanced non-small-cell lung cancer (NSCLC) remains a significant clinical challenge.
• Current first-line treatments often have limited efficacy and considerable toxicity.
• The role of immune checkpoint inhibitors in NSCLC is an area of active research.

Purpose of the Study:

• To review clinical trials evaluating pembrolizumab as a first-line therapy for advanced non-small-cell lung cancer (NSCLC).
• To assess the efficacy and safety of pembrolizumab, alone and in combination, in specific NSCLC patient populations.

Main Methods:

• Review of Phase III KEYNOTE-024 study data for pembrolizumab monotherapy versus chemotherapy in NSCLC with PD-L1 expression ≥50%.
• Analysis of Phase I/II KEYNOTE-021 cohort G data for pembrolizumab plus chemotherapy versus chemotherapy alone in nonsquamous NSCLC.

Main Results:

• Pembrolizumab monotherapy significantly improved progression-free survival and overall survival with fewer adverse events compared to chemotherapy in NSCLC with high PD-L1 expression.
• Combination therapy with pembrolizumab, pemetrexed, and carboplatin significantly improved objective response rate and progression-free survival in nonsquamous NSCLC with manageable toxicity.

Conclusions:

• Pembrolizumab demonstrates significant clinical benefit as a first-line treatment for advanced NSCLC in selected patient groups.
• These findings support the integration of pembrolizumab into the first-line management of advanced NSCLC, altering current treatment paradigms.