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

Updated: Jul 15, 2021
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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A second PD-1 inhibitor, pembrolizumab, was approved for metastatic NSCLC. Approval was based on data from the KEYNOTE-001 trial, in which pembrolizumab produced an overall response rate (ORR) of nearly 20% in 495 previously treated and treatment-naive patients with advanced or metastatic NSCLC. The ORR 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 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. [192]

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). [193]

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%). [194]

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