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

Julie E Bauman; Jonathan Harris; Ravindra Uppaluri; Min Yao; Robert L Ferris; Josephine Chen; Richard C Jordan; Nikhil P Joshi; Srinivas Jujjuvaparu; Dukagjin M Blakaj; Christina Henson; Jawad Sheqwara; Loren K Mell; Neilayan Sen; David A Clump; Madhur K Garg; Emrullah Yilmaz; Pedro Torres-Saavedra; Quynh-Thu Le

doi:10.3390/cancers13122882

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

Cancers (Basel). 2021 Jun 9;13(12):2882. doi: 10.3390/cancers13122882.

Authors

Julie E Bauman¹, Jonathan Harris², Ravindra Uppaluri³, Min Yao⁴, Robert L Ferris⁵, Josephine Chen⁶, Richard C Jordan⁷, Nikhil P Joshi⁸, Srinivas Jujjuvaparu⁹, Dukagjin M Blakaj¹⁰, Christina Henson¹¹, Jawad Sheqwara¹², Loren K Mell¹³, Neilayan Sen¹⁴, David A Clump⁵, Madhur K Garg¹⁵, Emrullah Yilmaz¹⁶, Pedro Torres-Saavedra², Quynh-Thu Le¹⁷

Affiliations

¹ University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
² NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, PA 19102, USA.
³ Dana Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA 02115, USA.
⁴ University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
⁵ UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA.
⁶ Department of Radiation Oncology, Kaiser Permanente, Dublin, CA 94568, USA.
⁷ NRG Oncology Biospecimen Bank, University of California San Francisco, San Francisco, CA 94143, USA.
⁸ Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, USA.
⁹ Illinois CancerCare PC, Peoria, IL 61615, USA.
¹⁰ Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
¹¹ University of Oklahoma Health Sciences Center, University of Oklahoma, Oklahoma City, OK 73104, USA.
¹² Henry Ford Health Institute, Detroit, MI 48202, USA.
¹³ University of California San Diego Moores Cancer Center, University of California, La Jolla, CA 92093, USA.
¹⁴ Rush University Medical Center, Rush University, Chicago, IL 60612, USA.
¹⁵ Montefiore Medical Center, Bronx, NY 10467, USA.
¹⁶ University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM 87102, USA.
¹⁷ Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.

Abstract

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.

Keywords: adjuvant; cisplatin; head and neck cancer; pathologically high-risk; pembrolizumab; phase I; radiation therapy.

Abstract

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