In patients with advanced basal cell carcinoma (BCC), treatment with the programmed cell death-1 (PD-1) inhibitor pembrolizumab has a reasonable safety profile and has demonstrated efficacy, according to the results published in the Journal of the American Academy of Dermatology.
The investigators sought to explore whether use of the PD-1 inhibitor pembrolizumab (200 mg administered intravenously every 3 weeks), with or without vismodegib (150 mg administered orally per day), is effective and safe in eligible patients with advanced BCC. Investigators conducted a proof-of-principle, nonrandomized, open-label study at the Stanford University School of Medicine. The primary study outcome was overall response rate (ORR) for all evaluable participants at 18 weeks.
A total of 16 patients were enrolled in the study — 9 of whom received pembrolizumab monotherapy and 7 of whom received pembrolizumab plus vismodegib combination therapy. All patients were assessed using revised Response Evaluation Criteria in Solid Tumors (version 1.1) at data cutoff.
The ORR was 38% (6 of 16) for all evaluable participants (95% CI, 15%-65%; P =.003) at 18 weeks. The ORR in the pembrolizumab monotherapy arm was 44% (4 of 9 patients; 95% CI, 14%-79%; P =.008) at 18 weeks. In the combination therapy arm, the ORR at 18 weeks was 29% (2 of 7 patients; 95% CI, 4%-71%; P =.15).
For all responders (n=6), the median time to response was 10.4 weeks (range, 8.4-17.4 weeks). The median duration of response was 67.3 weeks (range, 28.0-82.0 weeks) among all 6 responders. At 1 year, the probability of progression-free survival was 70% and the probability of overall survival was 94% among all evaluable participants.
No life-threatening adverse events (AEs) or deaths were reported during the study. Of 98 AEs reported among the 16 participants, 3 were considered severe (ie, grade 3). Of the 3 severe AEs, only 1 — hyponatremia — was attributed to pembrolizumab use.
The investigators concluded that pembrolizumab is active against BCC. Although there was no direct comparison between the 2 groups of patients, the response rate in the pembrolizumab plus vismodegib group was not superior to that in the pembrolizumab monotherapy group.
A major limitation of this study is the small sample size, as advanced BCC is an uncommon disease. The efficacy and safety data from this study could be used in future meta-analyses and compared with forthcoming multi-institutional studies on PD-1 inhibitors that are active against advanced BCC.
Chang ALS, Tran DC, Cannon JGD, et al. Pembrolizumab for advanced basal cell carcinoma: an investigator-initiated, proof-of-concept study [published online August 23, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.08.017