The Phase 3 KEYNOTE-789 trial, evaluating pembrolizumab in combination with chemotherapy for patients with EGFR-mutated metastatic non-small cell lung cancer (NSCLC) who had progressed on EGFR-tyrosine kinase inhibitor (TKI) therapy, did not meet its primary endpoint of overall survival (OS). The study's findings indicate that adding pembrolizumab to chemotherapy did not provide a statistically significant improvement in OS compared to chemotherapy alone in this patient population.
Study Design and Patient Population
KEYNOTE-789 was a randomized, double-blind, Phase 3 clinical trial designed to assess the efficacy and safety of pembrolizumab plus chemotherapy versus placebo plus chemotherapy in patients with EGFR-mutated metastatic NSCLC who had experienced disease progression following treatment with an EGFR-TKI. The trial enrolled patients with confirmed EGFR mutations and documented progression on or after EGFR-TKI therapy. The primary endpoint was overall survival, with secondary endpoints including progression-free survival (PFS) and objective response rate (ORR).
Key Findings
The results of the KEYNOTE-789 trial indicated that the addition of pembrolizumab to chemotherapy did not significantly improve overall survival in patients with EGFR-mutated metastatic NSCLC following EGFR-TKI therapy. Furthermore, no statistically significant differences were observed in progression-free survival or objective response rate between the pembrolizumab plus chemotherapy arm and the chemotherapy alone arm. These findings suggest that pembrolizumab does not offer a clinical benefit in this specific patient population.
Implications for Clinical Practice
These results do not support the use of pembrolizumab in combination with chemotherapy for patients with EGFR-mutated metastatic NSCLC who have progressed on EGFR-TKI therapy. The study underscores the importance of identifying predictive biomarkers to guide treatment decisions and highlights the need for alternative therapeutic strategies for this challenging patient population.
