From the Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston (M.R.M.), and South Texas Accelerated Research Therapeutics (START), San Antonio (K.P.P.) - both in Texas; the Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (D.R., A.A.T.), the Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, VIC (A.G.), the Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA (A.M.L.), and Royal Brisbane and Women's Hospital and University of Queensland, Brisbane (B.G.M.H.) - all in Australia; the Department of Dermatology, Brigham and Women's Hospital (C.D.S.), the Department of Dermatology, Harvard Medical School (C.D.S.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (G.R.) - all in Boston; Schleswig-Holstein University Hospital, Kiel (A.H.), and University Hospital Essen, Essen and German Cancer Consortium, Essen (D.S.) - both in Germany; University of Colorado Denver, School of Medicine, Aurora (K.D.L.); the Departments of Head and Neck-Endocrine Oncology (C.H.C.) and Cutaneous Oncology (N.I.K.), H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; the Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis (L.H.-A.); the Department of Dermatology, Stanford University School of Medicine, Redwood City (A.L.S.C.), and the Division of Dermatology, City of Hope, Duarte (B.M.) - both in California; the Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York (L.A.D.), and Regeneron Pharmaceuticals, Tarrytown (F.S., M.M., K.M., G.D.Y., I.L., M.G.F.) - both in New York; Regeneron Pharmaceuticals, Basking Ridge, NJ (B.G., S.L., J.L., J.B., E.S.); University of Arizona Cancer Center, Tucson (H.M.B.), and Banner MD Anderson Cancer (J.H.) and the Department of Medical Oncology, Banner MD Anderson Cancer Center (J.N.), Gilbert - all in Arizona; Medical Oncology Department, Vall D'Hebron University Hospital (I.B.), and Institut Català D'Oncologia, Oncobell Program (IDIBELL), L'Hospitalet de Llobregat (M.G.-M.), Barcelona, and START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid (V.M.) - all in Spain; Sarah Cannon Research Institute, Nashville (M.L.J.); and the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta (T.K.O.).
N Engl J Med. 2018 Jul 26;379(4):341-351. doi: 10.1056/NEJMoa1805131. Epub 2018 Jun 4.
No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.
We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review.
In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.
Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).
目前尚无系统疗法获批用于治疗晚期皮肤鳞状细胞癌。此类癌症可能对免疫疗法有反应，因为肿瘤的突变负担较高，且疾病风险与免疫抑制密切相关。在 1 期 cemiplimab 剂量递增研究中，转移性皮肤鳞状细胞癌患者观察到深度且持久的应答。
我们报告了 cemiplimab 用于局部晚期或转移性皮肤鳞状细胞癌扩展队列患者的 1 期研究结果，以及用于转移性疾病队列（转移性疾病队列）患者的关键 2 期研究结果。在两项研究中，患者每 2 周接受一次静脉 cemiplimab （3mg/kg 体重），每 8 周评估一次应答。在 2 期研究中，主要终点为独立中心评估的反应率。
在 1 期研究的扩展队列中，26 例患者中有 13 例（50%；95%置信区间 [CI]，30%至 70%）对 cemiplimab 有反应。在 2 期研究的转移性疾病队列中，59 例患者中有 28 例（47%；95%CI，34%至 61%）有反应。2 期研究转移性疾病队列的中位随访时间为 7.9 个月。在 28 例有反应的患者中，57%的患者反应持续时间超过 6 个月，82%的患者继续有反应，并在数据截止时继续接受 cemiplimab 治疗。在 2 期研究的转移性疾病队列中，至少 15%的患者发生的不良反应为腹泻、疲劳、恶心、便秘和皮疹；7%的患者因不良反应而停止治疗。
在晚期皮肤鳞状细胞癌患者中，cemiplimab 诱导约一半患者有反应，并伴有免疫检查点抑制剂常见的不良反应。（由 Regeneron Pharmaceuticals 和 Sanofi 资助；ClinicalTrials.gov 编号，NCT02383212 和 NCT02760498）。
