First-line pembrolizumab effective, safe in unresectable cutaneous squamous cell carcinoma
Pembrolizumab monotherapy appeared to be effective and safe as first-line treatment for patients with unresectable cutaneous squamous cell carcinoma, according to results of a phase 2 study published in Journal of Clinical Oncology.
“Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer, [and] its incidence has increased over the last decades worldwide,” Eve Maubec, MD, PhD, clinical researcher in the department of dermatology at Avicenne Hospital in France, and colleagues wrote. “CSCCs often occur in the elderly and men. Population aging, increasing numbers of organ transplant recipients, and evolution of attitudes toward ultraviolet exposure contribute to this increasing incidence.”
Maubec and colleagues assessed the efficacy and safety of the anti-PD-1 therapy pembrolizumab (Keytruda, Merck), dosed at 200 mg every 3 weeks, as first-line monotherapy for patients with unresectable CSCC.
Objective response rate at week 15 among the 39-patient primary cohort (median age, 79 years; 79% men) served as the primary endpoint. Secondary endpoints included best ORR, OS, PFS, duration of response, safety, ORR according to PD-L1 status and health-related quality of life.
Researchers also recruited an 18-patient expansion cohort (median age, 80 years; 83% men) to evaluate the difference in ORR at week 15 between patients with PD-L1-positive and PD-L1-negative disease.
Results showed an ORR at week 15 of 41% (95% CI, 26-58) among the primary cohort, including 13 partial and three complete responses. Eight patients achieved complete response between week 9 and week 72.
At median follow-up of 22.4 months, researchers observed median PFS of 6.7 months and median OS of 25.3 months among the primary cohort. Median duration of response had not been reached.
Among all patients, results showed an ORR of 42%, with a higher ORR for patients with PD-L1-positive vs. PD-L1-negative disease (55% vs. 17%; P = .025).
Functional Assessment of Cancer Therapy-General (FACT-G) scores showed meaningful improvement in health-related quality of life from baseline to week 15 among responders compared with nonresponders (P = .025).
Seventy-one percent of patients experienced treatment-related adverse events, the most common of which included fatigue (18%), diarrhea (13%) and hypothyroidism (13%). Four patients experienced grade 3 or higher events. One patient died due to rapid disease progression.
“The results of this prospective trial of rst-line pembrolizumab monotherapy for patients with unresectable CSCCs demonstrated its efcacy,” Maubec and colleagues wrote. “Pembrolizumab had robust antitumor activity, with sustained responses and manageable safety in this setting, conrming the interest of checkpoint inhibitors in treating CSCCs.”