In the French phase II CARSKIN trial reported in the Journal of Clinical Oncology, Maubec et al found that pembrolizumab monotherapy produced durable responses in the first-line treatment of unresectable cutaneous squamous cell carcinoma.

Study Details

In the multicenter trial, 39 patients (primary cohort) enrolled between March 2017 and September 2018 received 200 mg of pembrolizumab every 3 weeks for ≤ 24 months until disease progression or unacceptable toxicity. The primary endpoint was objective response rate at week 15 in the primary cohort. An expansion cohort of 18 patients was added to power the study to evaluate the week 15 objective response rate difference between PD-L1–positive and PD-L1–negative patients.

Responses

In the primary cohort, objective response at week 15 was observed in 15 patients (41%), including 13 partial and 3 complete responses. The disease control rate at 15 weeks was 54%. Best responses were eight partial and eight complete responses. Median time to response was 9 weeks (range = 8–15 weeks); median time to complete response was 24 weeks (range = 8–71 weeks). After a median follow-up of 22.4 months, median duration of response was not reached, with none of the 16 responders experiencing subsequent disease progression; the probability of maintaining response at week 48 was 93%. Median progression-free survival was 6.7 months (95% confidence interval [CI] = 15 weeks–not estimable). Median overall survival was 25.3 months (95% CI = 14.2 months–not estimable), with estimated 6- and 12-month rates of 81.3% and 75.5%.

Among all 57 patients, objective response at week 15 was observed in 24 patients (42%), with a disease control rate of 60%. Objective response was observed in 55% of 42 patients with PD-L1–positive disease at baseline vs 17% of 12 patients with PD-L1–negative disease (P = .02).

Adverse Events

Treatment-related adverse events of any grade occurred in 71% of patients, with the most common being fatigue (18%), diarrhea (13%), hypothyroidism (13%), pruritus (11%), and eczematous eruption (11%). Grade ≥ 3 treatment-related adverse events occurred in 7% of patients and consisted of diarrhea, colitis, cholestasis, cutaneous vasculitis, cutaneous squamous cell carcinoma hyperprogression, and second de novo head and neck cancer in one patient each. Treatment-related adverse events led to discontinuation of treatment in six patients. Adverse events led to death in two patients, with causes consisting of cutaneous squamous cell carcinoma hyperprogression and second de novo head and neck cancer.

The investigators concluded, “First-line pembrolizumab monotherapy exhibited promising anti– cutaneous squamous cell carcinoma activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.”

Eve Maubec, MD, PhD, of Hôpital Avicenne, Service de Dermatologie, Bobigny, France, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Merck Sharp & Dohme. For full disclosures of the study authors, visit ascopubs.org.