TY - JOUR
T1 - Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck
AU - Hanna, Glenn J.
AU - O'Neill, Anne
AU - Shin, Kee Young
AU - Wong, Kristine
AU - Jo, Vickie Y.
AU - Quinn, Charles T.
AU - Cutler, Jennifer M.
AU - Flynn, Michelle
AU - Lizotte, Patrick H.
AU - Annino, Donald J.
AU - Goguen, Laura A.
AU - Kass, Jason I.
AU - Rettig, Eleni M.
AU - Sethi, Rosh K.V.
AU - Lorch, Jochen H.
AU - Schoenfeld, Jonathan D.
AU - Margalit, Danielle N.
AU - Tishler, Roy B.
AU - Everett, Peter C.
AU - Desai, Anupam M.
AU - Cavanaugh, Megan E.
AU - Paweletz, Cloud P.
AU - Egloff, Ann Marie
AU - Uppaluri, Ravindra
AU - Haddad, Robert I.
N1 - Funding Information:
G.J. Hanna reports grants from Bristol Myers Squibb during the conduct of the study as well as grants and personal fees from Bicara, Exicure, Regeneron, BMS, and Sanofi Genzyme; grants from Gateway for Cancer Research, GSK, Kite Pharma, NantKwest/Altor Bioscience, and Secura Bio; and personal fees from Maverick and Merck outside the submitted work. V.Y. Jo reports “my spouse works as a Principal Scientist at Merck and Co for which he receives a salary, but his line of work in non-oncology has no relevant conflicts with this present study.” J.H. Lorch reports grants and personal fees from Novartis and Bayer and grants from Bristol Myers Squibb and Takeda outside the submitted work. J.D. Schoenfeld reports grants from BMS during the conduct of the study as well as grants from Merck, BMS, Regeneron, and Debiopharm and personal fees from Genentech, Immunitas, Debiopharn, LEK, Catenion, ACI Clinical, Astellas, and Stimit outside the submitted work. R.B. Tishler reports other support from PSI, Enzychem, and Regeneron outside the submitted work. P.C. Everett reports other support from Dana-Farber/Harvard Cancer Center (DF/HCC) during the conduct of the study. A.M. Desai reports other support from BMS during the conduct of the study. R. Uppaluri reports other support from Merck Inc outside the submitted work. R.I. Haddad reports grants from BMS during the conduct of the study as well as grants and personal fees from Merck, BMS, Pfizer, GSK, Merck Serono, Eisai, Bayer, AstraZeneca, Kura, NCCN, Nanobiotix, ISA, and Mirati outside the submitted work. No disclosures were reported by the other authors.
Publisher Copyright:
© 2021 The Authors.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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 receivedN (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, PDL1 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%). PDL1 combined positive score (CPS) at surgery was similar regardless of pathologic response (P = 0.71). Thirteen (46%) recurred (locoregional = 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)adjuvantN 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.
AB - 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 receivedN (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, PDL1 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%). PDL1 combined positive score (CPS) at surgery was similar regardless of pathologic response (P = 0.71). Thirteen (46%) recurred (locoregional = 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)adjuvantN 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.
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U2 - 10.1158/1078-0432.CCR-21-2635
DO - 10.1158/1078-0432.CCR-21-2635
M3 - Article
C2 - 34667025
AN - SCOPUS:85122493800
SN - 1078-0432
VL - 28
SP - 468
EP - 478
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 3
ER -
