Pilot Phase II Trial of Neoadjuvant Immunotherapy in Locoregionally Advanced, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck.

Abstract

PURPOSE:

In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence.

PATIENTS AND METHODS:

Newly diagnosed or recurrent stage III-IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response.

RESULTS:

Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9-54.3] had partial responses by RECIST, 14 patients (70%; 95% CI, 45.7-88.1) had a pCR (n = 11) or MPR (n = 3). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7-26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9-100), 89.5% (95% CI, 76.7-100), and 95% (95% CI, 85.9-100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8+ T-cell cluster enriched in patients with pCR.

CONCLUSIONS:

Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment.

• Authors: Renata Ferrarotto, Moran Amit, Priyadharsini Nagarajan, M Laura Rubin, Ying Yuan, Diana Bell, Adel K El-Naggar, Jason M Johnson, William H Morrison, David I Rosenthal, Bonnie S Glisson, Faye M Johnson, Charles Lu, Frank E Mott, Bita Esmaeli, Eduardo M Diaz Jr, Paul W Gidley, Ryan P Goepfert, Carol M Lewis, Randal S Weber, Jennifer A Wargo, Sreyashi Basu, Fei Duan, Shalini S Yadav, Padmanee Sharma, James P Allison, Jeffrey N Myers, Neil D Gross
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 16 Pg. 4557-4565 (08 15 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 34187851 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• Immune Checkpoint Inhibitors

Topics

• Aged
• Female
• Head and Neck Neoplasms (drug therapy, pathology, surgery)
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Immunotherapy
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Pilot Projects
• Skin Neoplasms (drug therapy, pathology, surgery)
• Squamous Cell Carcinoma of Head and Neck (drug therapy, pathology, surgery)