TY - JOUR
T1 - Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer
T2 - Optima paradigm expanded experience
AU - Rosenberg, Ari J.
AU - Agrawal, Nishant
AU - Pearson, Alexander
AU - Gooi, Zhen
AU - Blair, Elizabeth
AU - Cursio, John
AU - Juloori, Aditya
AU - Ginat, Daniel
AU - Howard, Adam
AU - Chin, Jeffrey
AU - Kochanny, Sara
AU - Foster, Corey
AU - Cipriani, Nicole
AU - Lingen, Mark
AU - Izumchenko, Evgeny
AU - Seiwert, Tanguy Y.
AU - Haraf, Daniel
AU - Vokes, Everett E.
N1 - Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AJR reports research support paid to the institution: Merck, BMS, Celgene; Consulting/Scientific Advisory Board: Nanobiotix, EMD-Serono. AP reports salary support NIH K08-DE026500 and NIH U01-CA243075, and serves on advisory board for Prelude Therapeutics. AJ reports research funding from AstraZeneca. TYS has received honoraria and institutional grants from Merck, Nanobiotix, and Regeneron; honoraria from Innate Pharma, eTheRNA, BioNTech, and Nektar; and institutional grants from Bristol Myers Squibb, and AstraZeneca, all outside the submitted work. EEV reports consultant/advisory roles for AbbVie, AstraZeneca, Beigene, BioNTech, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Merck, and Novartis. ZG, EB, JC, DG, AH, JC, SK, CF, NC, ML, EI, and DH report no conflicts of interest.
Funding Information:
This study was supported by Celgene, Alinea benefit supported by Grant Achatz/Nick Kokonas, and the National Cancer Institution of the National Institutes of Health (NIH) through Grant Number P30 CA14599.
Publisher Copyright:
© 2021
PY - 2021/11
Y1 - 2021/11
N2 - Background: Favorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. Methods: A phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30–50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). Results: 91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). Conclusion: Risk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.
AB - Background: Favorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. Methods: A phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30–50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). Results: 91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). Conclusion: Risk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.
KW - Chemotherapy
KW - Head and neck cancer
KW - Human papillomavirus
KW - Radiation therapy
KW - Treatment de-intensification
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U2 - 10.1016/j.oraloncology.2021.105566
DO - 10.1016/j.oraloncology.2021.105566
M3 - Article
C2 - 34662771
AN - SCOPUS:85117077966
VL - 122
JO - Oral Oncology
JF - Oral Oncology
SN - 1368-8375
M1 - 105566
ER -