Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)

Abstract

Purpose: Treatment options are limited for patients with recurrent and/or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC); mortality rates exceed 70% in patients with distant metastases. Here, we present the first interim analysis of the R/M cSCC cohort from the 2-cohort-locally advanced and R/M-phase II KEYNOTE-629 study.

Patients and methods: Patients with R/M cSCC not amenable to surgery or radiation received pembrolizumab 200 mg every 3 weeks. The primary end point was objective response rate per RECIST v1.1. Secondary end points were duration of response, disease control rate, progression-free survival, overall survival, and safety.

Results: At data cutoff (April 8, 2019), median follow-up of 105 enrolled patients in the R/M cohort was 11.4 months (range, 0.4 to 16.3 months). Objective response rate was 34.3% (95% CI, 25.3% to 44.2%; 4 complete responses, 32 partial responses), and disease control rate was 52.4% (95% CI, 42.4% to 62.2%). Median duration of response was not reached (range, 2.7 to 13.1+ months; '+' refers to ongoing response at data cutoff). Median progression-free survival was 6.9 months (95% CI, 3.1 months to 8.5 months). Median overall survival was not reached (95% CI, 10.7 months to not reached). Treatment-related adverse events occurred in 66.7% of patients (n = 70), the most common of which were pruritus (n = 15; 14.3%), asthenia (n = 14; 13.3%), and fatigue (n = 13; 12.4%). Grade 3 to 5 treatment-related adverse events occurred in 5.7% (n = 6) of patients. One patient died of treatment-related cranial nerve neuropathy.

Conclusion: Pembrolizumab demonstrated effective antitumor activity; clinically meaningful, durable responses; and acceptable safety in primarily elderly patients with R/M cSCC, supporting its use in clinical practice. Pembrolizumab adverse events in this study were consistent with its established safety profile.

Trial registration: ClinicalTrials.gov NCT03284424.

FIG 1.

(A) Best percentage change from baseline in target lesion and (B) duration of study treatment and response in responders (n = 36) in all patients as treated. All patients had at least one postbaseline assessment of target lesion(s) (n = 76). Symbols for complete response (CR), partial response (PR), and progressive disease depict the first response to pembrolizumab. Symbols depict the timing of first objective response unless otherwise indicated. (*) Discontinued or ongoing refers to status in relation to study treatment. (†) Patient achieved a best overall response (BOR) of CR.

FIG 2.

Effects of pembrolizumab monotherapy in patients with recurrent and/or metastatic cutaneous squamous cell carcinoma (cSCC). (A) An 80-year-old man with cSCC at the temple who previously underwent surgery at baseline (left), after 6 weeks of treatment (middle), and at the most recent follow-up (35 weeks; right). (B) An 87-year-old woman with cSCC at the jaw who previously received systemic therapy and radiation at baseline (left), after 6 weeks of treatment (middle), and at the most recent follow-up (37 weeks; right). (C) An 84-year-old woman with cSCC at the right axilla who previously underwent surgery and radiation at baseline (left), after 6 weeks of treatment (middle), and at the most recent follow-up (36 weeks; right). (D) A 92-year-old man with cSCC at the ear who previously received systemic therapy at baseline (left), after 6 weeks of treatment (middle), and at the most recent follow-up (62 weeks; right). Weeks are time since the date of the first dose of pembrolizumab.

FIG 2.

Effects of pembrolizumab monotherapy in patients with recurrent and/or metastatic cutaneous squamous cell carcinoma (cSCC). (A) An 80-year-old man with cSCC at the temple who previously underwent surgery at baseline (left), after 6 weeks of treatment (middle), and at the most recent follow-up (35 weeks; right). (B) An 87-year-old woman with cSCC at the jaw who previously received systemic therapy and radiation at baseline (left), after 6 weeks of treatment (middle), and at the most recent follow-up (37 weeks; right). (C) An 84-year-old woman with cSCC at the right axilla who previously underwent surgery and radiation at baseline (left), after 6 weeks of treatment (middle), and at the most recent follow-up (36 weeks; right). (D) A 92-year-old man with cSCC at the ear who previously received systemic therapy at baseline (left), after 6 weeks of treatment (middle), and at the most recent follow-up (62 weeks; right). Weeks are time since the date of the first dose of pembrolizumab.

FIG 3.

Kaplan-Meier estimates of (A) progression-free survival by blinded independent central review using RECIST v1.1 and (B) overall survival in all patients as treated. NR, not reached.