As reported in the Journal of Clinical Oncology by Grob et al, the first interim analysis of the phase II KEYNOTE-629 trial has shown that treatment with pembrolizumab resulted in durable responses in patients with recurrent or metastatic cutaneous squamous cell carcinoma.

The study supported the June 2020 U.S. Food and Drug Administration approval of pembrolizumab in recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation.

Study Details

The single-arm trial included 105 patients with recurrent or metastatic disease not amenable to surgery or radiation enrolled from sites in nine countries between October 2017 and June 2018. Patients were treated with pembrolizumab at 200 mg every 3 weeks for 35 doses (approximately 2 years) or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate on blinded independent central review using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints were duration of response, disease control rate, progression-free survival, overall survival, and safety.

Patients had a median age of 72; 80% were male; all had Eastern  Cooperative Oncology Group performance status of 0 (34%) or 1; PD-L1 status was combined positive score (CPS) ≥ 1 in 66% of patients, < 1 in 10%, and not available in 25%; 83% had stage IV disease; disease status was locoregional only in 45%, distant metastatic only in 24%, and both in 31%; 74% had received radiation and 80%, oncologic surgery; and 91% were receiving pembrolizumab as second- or later-line therapy. 

Efficacy Outcomes

At data cutoff in April 2019, median follow-up was 11.4 months (range = 0.4–16.3 months). Objective response was observed in 36 patients (34.3%, 95% confidence interval [CI] = 25.3%–44.2%), including complete response in 4 (3.8%). An additional 31 patients (29.5%) had stable disease, with 19 (18.1%) having stable disease for ≥ 12 weeks; the disease control rate (including stable disease ≥ 12 weeks) was 52.4% (95% CI = 42.4%–62.2%).

Median duration of response was not reached (range = 2.7–13.1+ months). Median time to response was 1.5 months (range = 1.2–5.7 months). Median progression-free survival was 6.9 months (95% CI = 3.1–8.5 months), with 6- and 12-month rates of 50.4% and 32.4%, respectively. Median overall survival was not reached (95% CI = 10.7 months–not reached), with 6- and 12-month rates of 79.0% and 60.3%.

Among 28 patients who received pembrolizumab beyond disease progression, 1 achieved complete response and 7 had partial response on immune-related RECIST criteria, with responses being ongoing in 4 patients at data cutoff.

Among the 14 patients receiving pembrolizumab as first-line treatment, objective response was observed in 7 (50%), including complete response in 2. Median progression-free survival was 8.3 months, and median overall survival was not reached. Among 91 patients receiving pembrolizumab as second-line or later treatment, objective response was observed in 29 (31.9%), with complete response in 2. Median progression-free survival was 5.4 months, and median overall survival was not reached.

Among 69 patients with PD-L1 CPS ≥ 1, objective response was observed in 23 (33.3%), with complete response in 2. Median progression-free survival was 5.4 months, and median overall survival was not reached. Among the 10 patients with PD-L1 CPS < 1, objective response was observed in 2 (10.0%), median progression-free survival was 4.2 months, and median overall survival was not reached.

Objective response rates were 36.2% in patients with locoregional-only disease; 32.8% in those with distant metastatic disease; 42.6% in patients with cutaneous squamous cell carcinoma tumors located primarily in the head and neck region; and 27.6% in patients with tumors in other primary locations.

Adverse Events

Treatment-related adverse events of any grade occurred in 70 patients (66.7%), with the most common being pruritus (14.3%), asthenia (13.3%), and fatigue (12.4%). Grade ≥ 3 treatment-related adverse events occurred in six patients (5.7%). Treatment-related serious adverse events occurred in seven patients (6.7%).

Adverse events irrespective of causality attribution led to treatment interruption in 28 patients (26.7%) and to treatment discontinuation in 13 (12.4%). One patient died from treatment-related cranial nerve neuropathy.

Immune-mediated adverse events were reported in 23 patients (21.9%), with the most common being hypothyroidism (9.5%), severe skin reactions (grade ≥ 3; 4.8%), pneumonitis (3.8%), adrenal insufficiency (2.9%), and hyperthyroidism (2.9%). No grade ≥ 4 immune-mediated adverse events were reported.

The investigators concluded, “Pembrolizumab demonstrated effective antitumor activity; clinically meaningful, durable responses; and acceptable safety in primarily elderly patients with [relapsed or metastatic] cutaneous squamous cell carcinoma, supporting its use in clinical practice. Pembrolizumab adverse events in this study were consistent with its established safety profile.”

Jean-Jacques Grob, MD, PhD, of Aix-Marseille University, Marseille, France, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc. For full disclosures of the study authors, visit ascopubs.org.