@article{7d3951715c8b4836abb3bf0816b75d19,
title = "A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma",
abstract = "Background: MET signaling is a well described mechanism of resistance to anti-EGFR therapy, and MET overexpression is common in head and neck squamous cell carcinomas (HNSCCs). In the current trial, the authors compared the oral MET inhibitor tivantinib (ARQ197) in combination with cetuximab (the TC arm) versus a control arm that received cetuximab monotherapy (C) in patients with recurrent/metastatic HNSCC. Methods: In total, 78 evaluable patients with cetuximab-naive, platinum-refractory HNSCC were enrolled, including 40 on the TC arm and 38 on the C arm (stratified by human papillomavirus [HPV] status). Patients received oral tivantinib 360 mg twice daily and intravenous cetuximab 500 mg/m2 once every 2 weeks. The primary outcome was the response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), and secondary outcomes included progression-free and overall survival. After patients progressed on the C arm, tivantinib monotherapy was optional. Results: The response rate was 7.5% in the TC arm (N = 3; 1 complete response) and 7.9% in the C arm (N = 3; not significantly different [NS]). The median progression-free survival in both arms was 4 months (NS), and the median overall survival was 8 months (NS). Both treatments were well tolerated, with a trend toward increased hematologic toxicities in the TC arm (12.5% had grade 3 leukopenia). The response rate in 31 HPV-positive/p16-positive patients was 0% in both arms, whereas the response rate in HPV-negative patients was 12.7% (12.5% in the TC arm and 13% in the C arm). Fifteen patients received tivantinib monotherapy, and no responses were observed. Conclusions: Combined tivantinib plus cetuximab does not significantly improve the response rate or survival compared with cetuximab alone but does increase toxicity in an unselected HNSCC population. Cetuximab responses appear to be limited to patients who have HPV-negative HNSCC. MET-aberration–focused trials for HNSCC and the use of higher potency, selective MET inhibitors remain of interest.",
keywords = "cetuximab, head and neck squamous cell carcinoma, human mesenchymal-epithelial transition factor (c-MET), metastatic disease, recurrent disease, tivantinib",
author = "Kochanny, {Sara E.} and Worden, {Francis P.} and Adkins, {Douglas R.} and Lim, {Dean W.} and Bauman, {Julie E.} and Wagner, {Stephanie A.} and Brisson, {Ryan J.} and Karrison, {Theodore G.} and Stadler, {Walter M.} and Vokes, {Everett E.} and Seiwert, {Tanguy Y.}",
note = "Funding Information: This work was supported by the National Cancer Institute?s Cancer Therapy Evaluation Program, ArQule Pharmaceuticals, and a grant from the Comprehensive Cancer Center at the University of Chicago. Funding Information: Francis P. Worden reports grants from Bristol‐Meyers Squibb, Merck & Company, Cue Biopharma, Eisai, Eli Lilly, Loxo Oncology, and Pfizer and personal fees from Merck & Company, Cue Biopharma, Bayer, and Loxo Oncology, all outside the submitted work. Douglas R. Adkins reports research funding from Phase 2 Consortium during the conduct of the study; grants from Pfizer, Eli Lilly, Merck & Company, Novartis, Celgene, AstraZeneca, Atara, Blueprint Medicine, CellCeutix, Celldex, Enzychem, Gliknik, Bristol‐Meyers Squibb, Kura, Medimmune, Exelixis, Innate, Matrix Biomed, Polaris, Cue Biopharma, and Sensei, outside the submitted work; and personal fees from Pfizer, Eli Lilly, Merck & Company, Celgene, Cue Biopharma, and Loxo Oncology outside the submitted work. Julie E. Bauman reports grants from Aduro, Aveo, Bristol‐Myers Squibb, Celldex, Cue Biopharma, Eli Lilly, Merck & Company, Moderna, and Novartis and personal fees from AstraZeneca, Cue Biopharma, EMD Serono, and Merck & Company, all outside the submitted work. Everett E. Vokes reports personal fees from AbbVie, Amgen, AstraZeneca, Biolumina, Bristol‐Myers Squibb, Celgene, Eli Lilly, EMD Serono, Genentech, Merck & Company, Novartis, and Regeneron, outside the submitted work. Tanguy Y. Seiwert reports grants from Bristol‐Myers Squibb, Jounce Therapeutics, and Merck & Company/Merck Sharpe & Dohme and personal fees from Aduro, AstraZeneca, Bayer, Bristol‐Myers Squibb, Celgene, Cue Biopharma, Genentech, Innate Pharmaceuticals, Loxo, Nanobiotix, Maverick, Merck & Company/Merck Sharpe & Dohme, Roche Diagnostics, and SQZ, all outside the submitted work. The remaining authors made no disclosures. Funding Information: This work was supported by the National Cancer Institute's Cancer Therapy Evaluation Program, ArQule Pharmaceuticals, and a grant from the Comprehensive Cancer Center at the University of Chicago. Publisher Copyright: {\textcopyright} 2020 American Cancer Society",
year = "2020",
month = may,
day = "15",
doi = "10.1002/cncr.32762",
language = "English",
volume = "126",
pages = "2146--2152",
journal = "Cancer",
issn = "0008-543X",
number = "10",
}