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
  • 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. [email protected].
  • 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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