Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial

Abstract

Background: Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). Patients and methods: KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab. Results: Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n ¼ 54; R/M cohort, n ¼ 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients. Conclusions: The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.

Neurotropic Cutaneous Malignancies: Case Report on Keratinocyte Derived Malignancies of the Head and Neck With Perineural Invasion

“…Post-hoc exploratory analysis of this cemiplimab study also showed symptomatic benefit with improvements in health-related quality of life and pain control ( 36 ). Similarly, the Phase II KEYNOTE-629 study with pembrolizumab reported an ORR of 50% in the locally advanced cohort and 35.2% in the recurrent/metastatic cohort, including a 16.7% and 10.5% CR rate, respectively ( 37 ). The median DOR was not reached in either cohort.…”

New Emerging Treatment Options for Advanced Basal Cell Carcinoma and Squamous Cell Carcinoma

“…CR and PR were observed in 20 and 44 treated patients, respectively. One hundred ten patients reported drug-related AEs with pruritus being the most represented one ( n = 29) [ 52 ].…”

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

“…In the la-cSCC cohort, the objective RR was 50.0% (95% CI, 36.1% to 63.9%), with 16.7% of patients achieving a CR and 33.3% a PR. In the recurrent or metastatic cSCC cohort, the objective RR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with CR and 24.8% with PR [ 62 , 63 ]. Moreover, the phase II CARSKIN trial (NCT02883556), involving 57 patients with unresectable cSCC, showed comparable results, with an objective RR of 42% (95% CI: 29–56%) and DCR of 60% (95% CI: 46–72%) [ 64 , 65 ].…”