What is the efficacy of pembrolizumab for 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...
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First-line combination treatment of pembrolizumab was approved in May 2017 for metastatic nonsquamous NSCLC. Approval was based on data from the KEYNOTE-021 trial (Cohort G1) in 123 previously untreated patients with metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations and irrespective of PD-L1 expression. In this trial, pembrolizumab plus pemetrexed and carboplatin demonstrated an ORR that was nearly double the ORR of pemetrexed/carboplatin (55% vs 29% respectively; all responses were partial responses). Among patients who received pembrolizumab plus pemetrexed/carboplatin, 93% had a duration of response of 6 months or more (range 1.4+ to 13.0+ months) compared to 81% who received pemetrexed/carboplatin alone (range 1.4+ to 15.2+ months). Progression free survival also improved (median 13.0 months [95% CI]) compared to 8.9 months (95% CI) with pemetrexed/carboplatin alone. [193]

In the KEYNOTE-010 trial, which compared pembrolizumab with docetaxel in 1034 patients with previously treated NSCLC who had PD-L1 expression on at least 1% of tumor cells, pembrolizumab resulted in longer overall survival and had a more favorable benefit-to-risk profile. In this randomized, open-label trial, median overall survival was 10.4 months with pembrolizumab 2 mg/kg, 12.7 months with pembrolizumab 10 mg/kg, and 8.5 months with docetaxel. [194]

In the KEYNOTE-189 trial, the addition of pembrolizumab to standard chemotherapy with pemetrexed and a platinum-based agent resulted in significantly longer overall and progression-free survival. The trial involved 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease. Study patients received either 200 mg of pembrolizumab or placebo every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. [195]

In KEYNOTE-189, 12-month survival was 69% with pembrolizumab versus 49% with placebo; median progression-free survival was 8.8 vs. 4.9 months, respectively. Survival benefit was seen in all subgroups receiving pembrolizumab, including those with a PD-L1 tumor proportion score of less than 1%, although the benefit was greater in patients with a higher score. [195]

Approval for treatment of metastatic squamous NSCLC with pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel was supported by the KEYNOTE-407 study. The combination of pembrolizumab plus chemotherapy (carboplatin and paclitaxel or nab-paclitaxel) significantly improved overall survival (OS) compared with chemotherapy alone, at a median of 15.9 months compared with 11.3 months (hazard ratio [HR], 0.64; P = 0.0017). [174]

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