Research in context
Evidence before this study
In August, 2016, we performed an extensive PubMed search for studies of PD-1, PD-L1, and CTLA-4 inhibitors in advanced cancer using the primary search terms of “PD-1 OR PD-L1 OR pembrolizumab OR MK-3475 OR lambrolizumab OR CTLA-4 OR ipilimumab OR nivolumab OR BMS-936558 OR atezolizumab OR MPDL3280A OR durvalumab OR MEDI4763 OR atezolizumab OR MSB0010718C OR BMS-936559.” Congress abstracts from annual oncology meetings were also included. Our search was not limited by date. The final reference list was generated on the basis of relevance to the scope of this paper.
Added value of this study
KEYNOTE-006 is the first head-to-head comparison of pembrolizumab versus ipilimumab for advanced melanoma. Interim analyses reported superiority of pembrolizumab to ipilimumab for overall survival, progression-free survival, and objective response rate, with fewer high-grade treatment-related toxicities with pembrolizumab. Results of the final analysis substantiated the survival advantage of pembrolizumab over ipilimumab and suggested that delayed responses with immunotherapy were possible. Importantly, this study showed that long-term treatment with pembrolizumab is well tolerated and efficacious.
Implications of all the available evidence
Pembrolizumab provides a favourable benefit-risk profile in comparison with ipilimumab, supporting pembrolizumab as a standard of care for advanced melanoma.