B G M Hughes1, E Munoz-Couselo2, L Mortier3, Å Bratland4, R Gutzmer5, O Roshdy6, R González Mendoza7, J Schachter8, A Arance9, F Grange10, N Meyer11, A Joshi12, S Billan13, P Zhang14, B Gumuscu14, R F Swaby14, J-J Grob15. 1. Cancer Care Services, Royal Brisbane and Women's Hospital, Herston, Australia; University of Queensland, Brisbane, Australia. Electronic address: brett.hughes@health.qld.gov.au. 2. Hospital Vall D Hebron and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 3. University of Lille, Inserm U 1189, CHU Lille, Lille, France. 4. Oslo Universitetssykehus, Oslo, Norway. 5. Department of Dermatology and Allergy, Skin Cancer Center Hannover, Medizinische Hochschule Hannover, Hanover, Germany; Mühlenkreiskliniken, Ruhr University Bochum Campus Minden, Minden, Germany. 6. Jewish General Hospital, Montreal, Canada. 7. Centro Estatal de Cancerologiade Chihuahua, Chihuahua, Mexico. 8. Chaim Sheba Medical Center at Tel HaShomer, Ramat Gan, Israel. 9. Hospital Clínic i Provincial de Barcelona, Barcelona, Spain. 10. Dermatology Department, Center Hospitalier Universitaire de Reims-Hôpital Robert Debre, Reims, France. 11. Dermatology, Institut Universitaire du Cancer and CHU de Toulouse, Toulouse, France. 12. Department of Medical Oncology, Townsville University Hospital, Townsville, Australia. 13. The Head and Neck Center, Oncology Department, Rambam Health Care Campus, Haifa, Israel. 14. Merck & Co., Inc., Kenilworth, USA. 15. Service de Dermatologie et Cancérologie Cutanée, Aix-Marseille University, Marseille, France.
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 = 54; R/M cohort, n = 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.
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 = 54; R/M cohort, n = 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.
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