NRG-HN003: Phase I and Expansion Cohort Study of Adjuvant Pembrolizumab, Cisplatin and Radiation Therapy in Pathologically High-Risk Head and Neck Cancer

Cancers

Nikhil P. Joshi¹  Ravindra Uppaluri²  Josephine Chen³  Quynh-Thu Le⁴  Jawad Sheqwara⁵  Srinivas Jujjuvaparu⁶  Madhur K. Garg⁷  Richard C. Jordan⁸  Jonathan Harris⁹  Pedro Torres-Saavedra⁹  Dukagjin M. Blakaj^1,10  Neilayan Sen^1,11  David A. Clump^1,12  Robert L. Ferris^1,12  Min Yao^1,13  Julie E. Bauman^1,14  Loren K. Mell^1,15  Emrullah Yilmaz^1,16  Christina Henson^1,17 

[1] Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, USA;Dana Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA 02115, USA;Department of Radiation Oncology, Kaiser Permanente, Dublin, CA 94568, USA;Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA;Henry Ford Health Institute, Detroit, MI 48202, USA;Illinois CancerCare PC, Peoria, IL 61615, USA;Montefiore Medical Center, Bronx, NY 10467, USA;NRG Oncology Biospecimen Bank, University of California San Francisco, San Francisco, CA 94143, USA;NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, PA 19102, USA;Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA;Rush University Medical Center, Rush University, Chicago, IL 60612, USA;UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA;University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA;University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA;University of California San Diego Moores Cancer Center, University of California, La Jolla, CA 92093, USA;University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM 87102, USA;University of Oklahoma Health Sciences Center, University of Oklahoma, Oklahoma City, OK 73104, USA;

关键词: head and neck cancer;    pathologically high-risk;    pembrolizumab;    adjuvant;    radiation therapy;    cisplatin;   

DOI  :  10.3390/cancers13122882

来源: DOAJ

【 摘 要 】

The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients with locoregional, pathologically high-risk HNSCC recur frequently despite adjuvant cisplatin–radiation therapy (CRT). Targeting PD1 may reverse immunosuppression induced by HNSCC and CRT. We conducted a phase I trial with an expansion cohort (n = 20) to determine the recommended phase II schedule (RP2S) for adding fixed-dose pembrolizumab to standard adjuvant CRT. Eligible patients had resected HPV-negative, stage III–IV oral cavity, pharynx, or larynx HNSCC with extracapsular nodal extension or positive margin. RP2S was declared if three or fewer dose-limiting toxicities (DLT) occurred in a cohort of 12. DLT was defined as grade 3 or higher non-hematologic adverse event (AE) related to pembrolizumab, immune-related AE requiring over 2 weeks of systemic steroids, or unacceptable RT delay. A total of 34 patients enrolled at 23 NRG institutions. During the first cohort, only one DLT was observed (fever), thus RP2S was declared as pembrolizumab 200 mg every 3 weeks for eight doses, starting one week before CRT. During expansion, three additional DLTs were observed (wound infection, diverticulitis, nausea). Of the 34 patients, 28 (82%) received five or more doses of pembrolizumab. This regimen was safe and feasible in a cooperative group setting. Further development is warranted.

【 授权许可】

Unknown