What is the role of pembrolizumab (Keytruda) in the treatment of metastatic non–small cell lung cancer (NSCLC)?

Updated: Jun 05, 2020
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
  • Print
Answer

In October 2015, a second PD-1 inhibitor, pembrolizumab (Keytruda), was approved for metastatic NSCLC. Approval of pembrolizumab was based in part on data from the KEYNOTE-001 trial, in which pembrolizumab produced an overall response rate of nearly 20% in 495 previously treated and treatment-naive patients with advanced or metastatic NSCLC. The overall response rate was much higher, at 45.2%, in a cohort of patients with NSCLC that showed high expression of PD-L1. The median duration of response exceeded 1 year (12.5 months) in all responders, regardless of the degree of PD-L1 expression. Median overall survival was 12.0 months (95% confidence interval [CI], 9.3–14.7 months) for all patients, 9.3 months (95% CI, 8.4–12.4 months) for previously treated patients, and 16.2 months (95% CI, 16.2 months–not reached) for previously untreated patients. [189]

In October 2016, pembrolizumab was approved as monotherapy for first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] ≥50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. This expanded approval was based on results from the KEYNOTE-024 trial, which showed significantly longer PFS and OS and fewer adverse events with pembrolizumab than with platinum-based chemotherapy. Median PFS was 10.3 months (95% CI, 6.7 to not reached) in the pembrolizumab group compared with 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P< 0.001). [191]

The above indication was expanded in April 2019 to include patients with stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (TPS ≥1%) with no EGFR or ALK genomic tumor aberrations. Approval was based on the KEYNOTE-042 trial (n=1274) that compared pembrolizumab with the investigator’s choice of platinum-based chemotherapy. Results suggest that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitizing EGFR or ALK alterations and with low PD-L1 TPS. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (ie, ≥50%, ≥20%, and ≥1%). [192]


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!