On October 30th, 2018, the FDA approved the use of programmed death 1 (PD-1) inhibitor pembrolizumab (Keytruda®, Merck) in combination with carboplatin plus paclitaxel or nab-paclitaxel for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC).

KEYNOTE-407

The multi-centre, double-blind, placebo-controlled KEYNOTE-407 (NCT02775435) study randomised 559 metastatic squamous NSCLC patients 1:1 to pembrolizumab or placebo plus carboplatin, and investigator’s choice (IC) paclitaxel or nab-paclitaxel for 4 cycles followed by maintenance pembrolizumab or placebo. Eligible patients had any PD-1 ligand (PD-L1) expression and did not receive prior systemic therapy in the metastatic setting. The treatment continued for up to 24 months or until progression disease (PD) or an unacceptable toxicity. The primary efficacy measures included the overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) as assessed by a blinded independent review committee (BIRC).

The results of the study showed significant improvements in OS, PFS, and ORR in favour of the addition of the PD-1 inhibitor pembrolizumab to IC chemotherapy compared to placebo plus IC chemotherapy. The median OS for pembrolizumab plus chemotherapy was 15.9 months vs 11.3 months for placebo plus chemotherapy (HR=0.64; 95% CI, 0.49-0.85; P=0.0017). The median PFS measured 6.4 months in patients receiving pembrolizumab plus chemotherapy and 4.8 months in patients receiving  placebo plus chemotherapy (HR=0.56; 95% CI, 0.45-0.70; P<0.0001). The ORR analysis was limited to the initial 204 randomised patients only. The ORR by BIRC measured 58% vs 35% with an estimated median response duration of 7.2 vs 4.9 months both for pembrolizumab plus chemotherapy vs placebo plus chemotherapy, respectively (ORR Δ=23.6%; 95% CI, 9.9-36.4; P=0.0008).

Safety

Common (≥20% of patients) adverse reactions in the pembrolizumab plus IC chemotherapy in the KEYNOTE-407 included fatigue/asthenia, nausea, constipation, diarrhoea, vomiting, pyrexia, decreased appetite, rash, cough, dyspnoea, alopecia, and peripheral neuropathy.

Keytruda® Prescribing Information