Clinical Data

The FDA approval was based on the KEYNOTE-189 (NCT02578680), a multicentre, double-blind, active-controlled study in the first-line treatment for metastatic non-squamous NSCLC and randomised 616 patients 2:1 to receive either pembrolizumab plus pemetrexed and investigator’s choice (IC) cisplatin or carboplatin or placebo plus pemetrexed and IC platinum salt. After four cycles of platinum-based chemotherapy, all patients continued to receive pemetrexed with either pembrolizumab or placebo for up to 24 months or until disease progression or unacceptable toxicity. The primary endpoints were overall survival (OS) and progression-free survival (PFS) by blinded independent central review using RECIST 1.1.

In the KEYNOTE-189, adding pembrolizumab to platinum-based chemotherapy was associated with an improved OS  when compared to placebo plus chemotherapy (HR=0.49; 95% CI, 0.38-0.64; p<0.00001). At the time of data cut-off, the median OS was not yet reached for patients receiving pembrolizumab plus chemotherapy and measured 11.3 months for patients randomised to placebo plus chemotherapy. The PFS in the pembrolizumab plus chemotherapy arm was 8.8 months vs 4.9 months in the placebo plus chemotherapy group (HR=0.52; 95% CI, 0.43-0.64; p<0.00001). The overall response rate (ORR) was significantly improved with the addition of pembrolizumab; 48% vs 19% in the placebo group (p=0.0001). Finally, the median duration of response was 11.2 months vs 7.8 months for pembrolizumab plus chemotherapy vs placebo plus chemotherapy, respectively.

In May 2017, the FDA granted accelerated approval for the same indication, based on the improved ORR and PFS for patients receiving treatment with the combination of the programmed death 1 (PD-1) inhibitor pembrolizumab and chemotherapy when compared to patients receiving chemotherapy alone in the KEYNOTE-021 study.