Research in context
Evidence before this study
We searched PubMed on Nov 2, 2015, using the following terms: “PD-1 OR PD-L1 OR MK-3475 OR pembrolizumab OR lambrolizumab OR Keytruda OR nivolumab OR BMS-936558 OR Opdivo OR atezolizumab OR MPDL3280A OR BMS-936559 OR durvalumab OR MEDI4736 OR avelumab OR MSB0010718C OR docetaxel” AND “non-small-cell lung cancer OR NSCLC”. The search was not limited by date. We also searched the abstracts for the 2014 and 2015 American Society of Clinical Oncology Annual Meetings, the 2014 European Society for Medical Oncology Congress, and the 2015 European Cancer Congress using the same search terms. We identified three randomised trials of anti-PD-1 or anti-PD-L1 treatment versus docetaxel for non-small-cell lung cancer: the CheckMate 017 study of nivolumab for squamous non-small-cell lung cancer, the CheckMate 057 study of nivolumab for non-squamous non-small-cell lung cancer, and the POPLAR study of atezolizumab for squamous and non-squamous non-small-cell lung cancer. We focused on the CheckMate studies because they are published in peer-reviewed journals.
Added value of this study
Results of KEYNOTE-010 confirm the efficacy and safety of PD-1 inhibition with pembrolizumab in patients with previously treated non-small-cell lung cancer. These data are the first published report of a randomised, controlled clinical trial of non-small-cell lung cancer that prospectively shows the utility of PD-L1 as a biomarker. This study is also the first of a PD-1 inhibitor for non-small-cell lung cancer to include patients who received more than one line of previous treatment. Both pembrolizumab 2 mg/kg and pembrolizumab 10 mg/kg every 3 weeks provided superior overall survival compared with docetaxel, with similar outcomes for each pembrolizumab dose. Pembrolizumab was also associated with fewer high-grade toxic effects than was docetaxel.
Implications of all the available evidence
Our data support pembrolizumab 2 mg/kg given every 3 weeks as a new treatment option for patients with non-small-cell lung cancer with a PD-L1 tumour proportion score of at least 1% that progressed after platinum-based chemotherapy and, in those with an EGFR sensitising mutation or an ALK translocation, an appropriate tyrosine kinase inhibitor. These data also validate the use of PD-L1 on tumour cells as a biomarker to identify patients most likely to obtain a benefit from pembrolizumab.