Pembrolizumab (Keytruda) is an IV applied monoclonal antibody, which is supposed to reduce tumour induced T-cell deactivation by PD-L1.

The FDA granted pembrolizumab accelerated approval and the breakthrough status for the new indication non-small cell lung cancer (NSCLC) in October 2015, based on KEYNOTE-001. This phase Ib-study delivered evidence supporting the efficacy and tolerability of the therapy in previously treated patients with advanced and PD-L1 expressing NSCLC. About 1000 persons in Austria are diagnosed every year with PD-L1 positive advanced NSCLC, mostly in advanced stages due to the late occurrence of symptoms. Thus far, the EMA approved pembrolizumab only for the indication melanoma. Keynote-001 showed improved efficacy (response rate 19.4%) and tolerability (10% adverse events of grade 3-5) of pembrolizumab in mostly PD-L1 positive patients.
KEYNOTE-010, a randomised, open-label phase III trial reports efficacy and adverse events (AEs) of pembrolizumab (in two different dosages) in comparison to docetaxel. Results showed superiority of pembrolizumab in median overall survival (17.3/14.9 months depending on dosage vs. 8.2 months), progression-free survival (5 vs. 4 months) in the subpopulation of patients with a PD-L1 expression of ≥50% and reduced AEs (16/13 % depending on dosage vs. 35%). A reliable and implementable PD-L1 test is thus crucial for an application of pembrolizumab in clinical routine. Smoking status is considered a predictive marker for therapeutic effect as well.

Generalisability of the results could be compromised due to the stringent inclusion criteria of ECOG-performance 0/1 and the relatively young median age (63 years) of the studied population. Open questions remain regarding the combination with other therapeutics and the comparison with other targeted therapies such as nivolumab. In addition, the benefit for patients with EGFR mutation needs to be further examined. Data for quality of life are still missing. Overall, KEYNOTE-010 reported a significantly improved OS with fewer side-effects compared to the chemotherapeutic docetaxel. Evidence is however still relatively scarce when it comes to patient related outcomes as well as long term effects, and to identify those patients who benefit most from pembrolizumab remains a challenge.