Pembrolizumab improves OS across PD-L1 subgroups

In 2016, KEYNOTE-024 established the superior efficacy of first-line pembrolizumab over chemotherapy for metastatic non-small-cell lung cancer (NSCLC) with a programmed cell death 1 ligand 1 (PD-L1) tumour proportion score (TPS) ≥50%. Now, overall survival (OS) data from the second interim analysis of KEYNOTE-042, which investigated the efficacy of pembrolizumab in patients with a lower PD-L1 TPS, have been reported.

The phase III trial enrolled 1,274 patients with previously untreated, PD-L1-positive (TPS ≥1%), locally advanced or metastatic NSCLC without a sensitizing EGFR or ALK alteration. Patients were randomized 1:1 to receive pembrolizumab or platinum-based chemotherapy. The primary end point was OS across three predefined subgroups (TPS ≥50%, ≥20% and ≥1%).

At a median follow-up duration of 12.8 months, OS was significantly longer in patients receiving pembrolizumab than in those receiving chemotherapy across all PD-L1 subgroups (TPS ≥50% HR 0.69, 95% CI 0.56–0.85, P = 0.0003; TPS ≥20% HR 0.77, 95% CI 0.64–0.92, P = 0.0020; TPS ≥1% HR 0.81, 95% CI 0.71–0.93, P = 0.0018). Median OS for pembrolizumab versus chemotherapy was 20.0 versus 12.2 months, 17.7 versus 13.0 months and 16.7 versus 12.1 months for the TPS ≥50%, ≥20% and ≥1% subgroups, respectively.

Any grade (63% versus 90%) and grade ≥3 (18% versus 42%) treatment-related adverse events (TRAEs) were lower with pembrolizumab. In each arm, TRAEs led to death in 2% and to treatment discontinuation in 9% of patients.

Overall, these findings have led the FDA to extend the indication for pembrolizumab to patients with a PD-L1 TPS as low as 1%.