Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer: OPTIMA II Phase 2 Open-Label Nonrandomized Controlled Trial.

Autor:	Rosenberg AJ; Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.; University of Chicago Comprehensive Cancer Center, Chicago, Illinois., Agrawal N; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, Illinois., Juloori A; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois., Cursio J; Department of Public Health Sciences, University of Chicago, Chicago, Illinois., Gooi Z; Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, Illinois., Blair E; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, Illinois., Chin J; Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois., Ginat D; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Department of Radiology, University of Chicago, Chicago, Illinois., Pasternak-Wise O; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Department of Radiology, University of Chicago, Chicago, Illinois., Hasina R; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, Illinois., Starus A; Sysmex-Inostics Inc, Baltimore, Maryland., Jones FS; Sysmex-Inostics Inc, Baltimore, Maryland., Izumchenko E; Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.; University of Chicago Comprehensive Cancer Center, Chicago, Illinois., MacCracken E; Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, Illinois., Wolk R; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Department of Pathology, University of Chicago, Chicago, Illinois., Cipriani N; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Department of Pathology, University of Chicago, Chicago, Illinois., Lingen MW; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Department of Pathology, University of Chicago, Chicago, Illinois., Pearson AT; Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.; University of Chicago Comprehensive Cancer Center, Chicago, Illinois., Seiwert TY; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland., Haraf DJ; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois., Vokes EE; Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.; University of Chicago Comprehensive Cancer Center, Chicago, Illinois.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2024 Jul 01; Vol. 10 (7), pp. 923-931.
DOI:	10.1001/jamaoncol.2024.1530
Abstrakt:	Importance: Immune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role in curative human papillomavirus-positive oropharyngeal cancer (HPV+ OPC) remains undefined. Neoadjuvant nivolumab and chemotherapy followed by response-adaptive treatment in HPV+ OPC may increase efficacy while reducing toxicity. Objective: To determine the deep response rate and tolerability of the addition of neoadjuvant nivolumab to chemotherapy followed by response-adapted locoregional therapy (LRT) in patients with HPV+ OPC. Design, Setting, and Participants: This phase 2 nonrandomized controlled trial conducted at a single academic center enrolled 77 patients with locoregionally advanced HPV+ OPC from 2017 to 2020. Data analyses were performed from February 10, 2021, to January 9, 2023. Interventions: Addition of nivolumab to neoadjuvant nab-paclitaxel and carboplatin (studied in the first OPTIMA trial) followed by response-adapted LRT in patients with HPV+ OPC stages III to IV. Main Outcomes and Measures: Primary outcome was deep response rate to neoadjuvant nivolumab plus chemotherapy, defined as the proportion of tumors with 50% or greater shrinkage per the Response Evaluation Criteria in Solid Tumors 1.1. Secondary outcomes were progression-free survival (PFS) and overall survival (OS). Swallowing function, quality of life, and tissue- and blood-based biomarkers, including programmed death-ligand 1 (PD-L1) expression and circulating tumor HPV-DNA (ctHPV-DNA), were also evaluated. Results: The 73 eligible patients (median [range] age, 61 [37-82] years; 6 [8.2%] female; 67 [91.8%] male) started neoadjuvant nivolumab and chemotherapy. Deep responses were observed in 51 patients (70.8%; 95% CI, 0.59-0.81). Subsequent risk- and response-adaptive therapy was assigned as follows: group A, single-modality radiotherapy alone or transoral robotic surgery (28 patients); group B, intermediate-dose chemoradiotherapy of 45 to 50 Gray (34 patients); and group C, regular-dose chemoradiotherapy of 70 to 75 Gray (10 patients). Two-year PFS and OS were 90.0% (95% CI, 0.80-0.95) and 91.4% (95% CI, 0.82-0.96), respectively. By response-adapted group, 2-year PFS and OS for group A were 96.4% and 96.4%, and group B, 88.0% and 91.0%, respectively. Lower enteral feeding rates and changes in weight, as well as improved swallowing, were observed among patients who received response-adapted LRT. Pathologic complete response rate among patients who underwent transoral robotic surgery was 67.0%. PD-L1 expression was nonsignificantly higher for deeper responses and improved PFS, and ctHPV-DNA clearance was significantly associated with improved PFS. Conclusions and Relevance: This phase 2 nonrandomized controlled trial found that neoadjuvant nivolumab and chemotherapy followed by response-adapted LRT is feasible and has favorable tolerability, excellent OS, and improved functional outcomes in HPV+ OPC, including among patients with high-risk disease. Moreover, addition of nivolumab may benefit high PD-L1 expressors, and sensitive dynamic biomarkers (eg, ctHPV-DNA) are useful for patient selection. Trial Registration: ClinicalTrials.gov Identifier: NCT03107182.
Databáze:	MEDLINE
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