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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number2882
JournalCancers
Volume13
Issue number12
DOIs
StatePublished - Jun 2 2021

Keywords

  • Adjuvant
  • Cisplatin
  • Head and neck cancer
  • Pathologically high-risk
  • Pembrolizumab
  • Phase I
  • Radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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