Subcutaneous pembrolizumab is a viable treatment option for mNSCLC

Prof Enriqueta Felip - Vall d'Hebron University Hospital, Barcelona, Spain

This was a phase III randomised open-label study including patients with untreated stage 4 non-small cell lung cancer with absence of EGFR, ALK and ROS alterations and with a good performance status. Patients were randomised to 2:1 randomisation to receive pembrolizumab in a subcutaneous formulation, 790mg every six weeks, versus pembrolizumab IV, 400mg every six weeks, in combination with platinum-based chemotherapy according to the histological subtype. 

Patients received up to 16 cycles of pembrolizumab and the trial had two dual primary endpoints, two PK endpoints – the cycle 1 area under the curve and also the steady state at cycle 3.

What were the results of this study?

In the trial 377 patients were randomised, 251 received pembrolizumab subcutaneous and 126 pembrolizumab IV. It’s important to stress that for those patients receiving pembrolizumab subcutaneously the median injection time was only 2 minutes for a 4.8ml [??]. Overall patient demographics were well balanced between the two treatment arms. Perhaps to highlight that 66% of the patients included had non-squamous histology, 33% of the patients had squamous histology and approximately 40% of the patients had tumours with PD-L1 negative staining.

It's important that the study is positive. The study was positive for the two dual primary endpoints. This was a non-inferiority trial trying to find that subQ was non-inferior to IV with a pre-specified non-inferiority margin geometric mean ratio of 0.8. For the cycle 1 area under the curve, the geometric mean ratio was 1.14. For the steady state at cycle 3 the geometric mean ratio was 1.67 so in both cases above the prespecified non-inferiority margin.

It's important also to analyse the results from an efficacy endpoint. So in the study the median PFS with pembrolizumab subQ plus chemotherapy was 8.1 months; with pembrolizumab IV plus chemotherapy it was 7.8 months with a hazard ratio of 1.05. So overall very similar results in efficacy, in PFS, also in overall response rate that was 45% for those patients treated with pembrolizumab subQ versus 42% response rate for those patients treated with pembrolizumab IV. Similar median duration of response – 9.1 months for pembrolizumab subQ, 8 months for pembrolizumab IV – and also no differences in overall survival that was immature, it was not reached in any of the treatment arms and the hazard ratio was 0.81.

Also, we presented adverse events that were pretty similar between the two treatment arms. So grade 3-5 treatment-related adverse events in 47% of the patients in the two treatment arms. 8% of the patients discontinued pembrolizumab subQ or IV, so exactly the same percentage of patients discontinued the treatment. When we analysed the injection site reactions, only six patients had any injection site adverse events. These represent 2.4% of the patients and in all cases they were grade 1.

What do you think is the clinical significance of these results?

The trial is a positive trial that demonstrated that pembrolizumab subQ was not inferior to pembrolizumab IV. It’s important also to say that the response rate, PFS and duration of response were consistent between the two treatment arms, pembrolizumab IV and pembrolizumab subQ. When we analysed the toxicity, for pembrolizumab subQ plus chemotherapy it was manageable and consistent with the toxicity with pembrolizumab IV. Also the injection site reactions were infrequent, mild and non-serious.

It’s important to say that the median injection time for pembrolizumab subQ was only two minutes and, in my opinion, pembrolizumab subQ is a treatment option in all indications where pembrolizumab IV can be used.

Is there anything else you would like to add?

It’s important to acknowledge and to thank the patients and their families and also all the investigator sites. Also that we are really pleased that the results of the trial were published simultaneously with the presentation at ELCC in Annals of Oncology. Thank you.