Pembrolizumab monotherapy may be an effective first-line therapy in patients with locally advanced or metastatic non-small-cell lung cancer with low programmed death ligand 1 (PD-L1) tumor proportion score (TPS) and without sensitizing EGFR or ALK alterations. Treatment with pembrolizumab may be more effective than chemotherapy for improving overall survival in this patient population, according to a phase 3 study published in the Lancet.
A total of 1274 patients with previously untreated locally advanced or metastatic non-small-cell lung cancer from 213 medical centers in 32 countries were enrolled in the KEYNOTE-042 study (ClinicalTrials.gov identifier: NCT02220894). Inclusion criteria were carcinoma without a sensitizing EGFR mutation or ALK translocation, Eastern Cooperative Oncology Group performance status score of 0 or 1, PD-L1 TPS of ≥1%, and a life expectancy ≥3 months.
Researchers randomly assigned patients (1:1) to either pembrolizumab 200 mg every 3 weeks for up to 35 cycles (n=637) or platinum-based chemotherapy for 4 to 6 cycles (n=637). The primary end point included overall survival in patients with a TPS of ≥50%, ≥20%, and ≥1% in the intention-to-treat population.
At time of enrollment, approximately 47% and 64% of patients had a TPS of ≥50% and ≥20%, respectively. During a median follow-up of 12.8 months, patients in the pembrolizumab group had longer overall survival compared with those in the chemotherapy group in the ≥50% TPS (hazard ratio, 0.69; 95% CI, 0.56-0.85; P =.0003), ≥20% TPS (hazard ratio, 0.77; 95% CI, 0.64-0.92; P =.0020), and ≥1% TPS (hazard ratio, 0.81; 95% CI, 0.71-0.93; P =.0018) groups.
A lower proportion of treatment-related adverse events of grade 3 or worse was observed in the pembrolizumab group vs the chemotherapy group (18% vs 41%, respectively). In addition, a similar proportion of deaths resulting from adverse events occurred in both the pembrolizumab and chemotherapy groups (2% vs 2%).
A potential limitation of the study included its open-label design.
“The results of KEYNOTE-042, in which overall survival was the primary endpoint,” the researchers wrote, “confirm the role of pembrolizumab monotherapy as a standard first-line treatment for non-small-cell lung cancer with high PD-L1 expression and suggest that it is a reasonable treatment option for patients with lower PD-L1 expression levels.”
Disclosures: This study was funded by Merck Sharp & Dohme.
Mok TSK, Wu Y-L, Kudaba I, et al; for the KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial [published online April 4, 2019]. Lancet. doi:10.1016/S0140-6736(18)32409-7