TY - JOUR
T1 - Pilot phase II trial of neoadjuvant immunotherapy in locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck
AU - Ferrarotto, Renata
AU - Amit, Moran
AU - Nagarajan, Priyadharsini
AU - Rubin, M. Laura
AU - Yuan, Ying
AU - Bell, Diana
AU - El-Naggar, Adel K.
AU - Johnson, Jason M.
AU - Morrison, William H.
AU - Rosenthal, David I.
AU - Glisson, Bonnie S.
AU - Johnson, Faye M.
AU - Lu, Charles
AU - Mott, Frank E.
AU - Esmaeli, Bita
AU - Diaz, Eduardo M.
AU - Gidley, Paul W.
AU - Goepfert, Ryan P.
AU - Lewis, Carol M.
AU - Weber, Randal S.
AU - Wargo, Jennifer A.
AU - Basu, Sreyashi
AU - Duan, Fei
AU - Yadav, Shalini S.
AU - Sharma, Padmanee
AU - Allison, James P.
AU - Myers, Jeffrey N.
AU - Gross, Neil D.
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research
PY - 2021/8/15
Y1 - 2021/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113786457&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-21-0585
DO - 10.1158/1078-0432.CCR-21-0585
M3 - Article
C2 - 34187851
AN - SCOPUS:85113786457
SN - 1078-0432
VL - 27
SP - 4557
EP - 4565
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -