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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

Author(s): Mok TSK, Wu YL, Kudaba I et al

Lancet. 2019 Apr 4. pii: S0140-6736(18)32409-7

Thoracic oncology
General respiratory patient care

Digest Author(s): Wouter H. van Geffen / 25 April, 2019

In a randomised, open-label, controlled, phase 3 trial the anti-programmed death 1 monoclonal antibody pembrolizumab was assessed for previously untreated advanced or metastatic NSCLC with a PD-L1 of ≥1%. The authors now report the overall survival and progression-free survival. In this study 1274 patients were enrolled. Patients were randomized to treatment with platinum-based chemotherapy or pembrolizumab monotherapy (200mg).

Overall survival was longer in the pembrolizumab group than in the chemotherapy group in all PD-L1 populations (≥50% hazard ratio 0.69, 95% CI 0.56–0.85, p=0.0003; ≥20% 0.77, 0.64–0.92, p=0.0020, and ≥1% 0.81, 0.71–0.93, p=0.0018). The median survival values by PD-L1 population were 20.0 months (95% CI 15.4–24.9) for pembrolizumab versus 12.2 months (10.4–14.2) for chemotherapy, 17.7 months (15.3–22.1) versus 13.0 months (11.6–15.3), and 16.7 months (13.9–19.7) versus 12.1 months (11.3–13.3), respectively. Severe toxicity occurred in 113 out of the pembrolizumab patients (18%) and in 252 (41%) of the chemotherapy patients.


This randomized study provides evidence that pembrolizumab monotherapy provides a sustainable effect on survival and acceptable safety for patients with previously untreated advanced or metastasized non-small-cell lung cancer compared with platinum-based chemotherapy in PD-L1 positive patients. However more research is needed, especially in the 1-49% PD-L1 group. Based on the currently presented results and especially the Kaplan-Meier estimates, it would be interesting to see a future trial comparing pembrolizumab monotherapy with pembrolizumab combined with platinum- based chemotherapy for these groups.