2. Academic Validation
  3. Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck

Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck

  • Clin Cancer Res. 2022 Feb 1;28(3):468-478. doi: 10.1158/1078-0432.CCR-21-2635.
Glenn J Hanna 1,  Anne O'Neill 2,  Kee-Young Shin 2,  Kristine Wong 3,  Vickie Y Jo 3,  Charles T Quinn 4,  Jennifer M Cutler 4,  Michelle Flynn 4,  Patrick H Lizotte 4 5,  Donald J Annino Jr 6,  Laura A Goguen 6,  Jason I Kass 7,  Eleni M Rettig 6,  Rosh K V Sethi 6,  Jochen H Lorch 4,  Jonathan D Schoenfeld 8,  Danielle N Margalit 8,  Roy B Tishler 8,  Peter C Everett 9,  Anupam M Desai 10,  Megan E Cavanaugh 4 5,  Cloud P Paweletz 4 5,  Ann Marie Egloff 6,  Ravindra Uppaluri  # 6,  Robert I Haddad  # 4
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. glenn_hanna@dfci.harvard.edu.
  • 2 Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 3 Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
  • 4 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 5 Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 6 Division of Otolaryngology-Head and Neck Surgery, Brigham and Women's Hospital and Head and Neck Surgical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 7 Reliant Medical Group, Worcester, Massachusetts.
  • 8 Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
  • 9 Department of Medical Oncology, Boston Medical Center, Boston, Massachusetts.
  • 10 Department of Hematology/Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
  • # Contributed equally.
PMID: 34667025 DOI: 10.1158/1078-0432.CCR-21-2635
Abstract

Purpose: Surgery often represents the best chance for disease control in locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We investigated dual immune-checkpoint inhibition [anti-PD-1, nivolumab (N), and anti-KIR, lirilumab (L)] before and after salvage surgery to improve disease-free survival (DFS).

Patients and methods: In this phase II study, patients received N (240 mg) + L (240 mg) 7 to 21 days before surgery, followed by six cycles of Adjuvant N + L. Primary endpoint was 1-year DFS; secondary endpoints were safety, pre-op radiologic response, and overall survival (OS). Correlatives included tumor Sequencing, PD-L1 scoring, and immunoprofiling.

Results: Among 28 patients, the median age was 66, 86% were smokers; primary site: 9 oral cavity, 9 oropharynx, and 10 larynx/hypopharynx; 96% had prior radiation. There were no delays to surgery. Grade 3+ adverse events: 11%. At the time of surgery, 96% had stable disease radiologically, one had progression. Pathologic response to N + L was observed in 43% (12/28): 4/28 (14%) major (tumor viability, TV ≤ 10%) and 8/28 (29%) partial (TV ≤ 50%). PD-L1 combined positive score (CPS) at surgery was similar regardless of pathologic response (P = 0.71). Thirteen (46%) recurred (loco-regional = 10, distant = 3). Five of 28 (18%) had positive margins, 4 later recurred. At median follow-up of 22.8 months, 1-year DFS was 55.2% (95% CI, 34.8-71.7) and 1-year OS was 85.7% (95% CI, 66.3-94.4). Two-year DFS and OS were 64% and 80% among pathologic responders.

Conclusions: (Neo)Adjuvant N + L was well tolerated, with a 43% pathologic response rate. We observed favorable DFS and excellent 2-year OS among high-risk, previously treated patients exhibiting a pathologic response. Further evaluation of this strategy is warranted.See related commentary by Sacco and Cohen, p. 435.

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