Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer: OPTIMA II Phase 2 Open-Label Nonrandomized Controlled Trial.
Key Points: Question: Is neoadjuvant nivolumab with chemotherapy followed by response-adapted locoregional therapy effective and well tolerated in patients with human papillomavirus−positive oropharyngeal carcinoma (HPV+ OPC)? Findings: This phase 2 nonrandomized controlled trial of 73 patients with...
| Publicado en: | JAMA Oncology Vol. 10; no. 7; pp. 923 - 932 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
American Medical Association
Jul2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=178534233&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 178534233 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23742437 I6NW jtl: JAMA Oncology issn: 23742437 maglogo: N pubinfo: dt: Jul2024 vid: 10 iid: 7 pid: 30 pub: American Medical Association place: Chicago, Illinois artinfo: ui: 178534233 178534233 178534233 10.1001/jamaoncol.2024.1530 178534233 ppf: 923 ppct: 9 formats: tig: atl: Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer: OPTIMA II Phase 2 Open-Label Nonrandomized Controlled Trial. aug: au: Rosenberg, Ari J. Agrawal, Nishant Juloori, Aditya Cursio, John Gooi, Zhen Blair, Elizabeth Chin, Jeffrey Ginat, Daniel Pasternak-Wise, Olga Hasina, Rifat Starus, Anna Jones, Frederick S. Izumchenko, Evgeny MacCracken, Ellen Wolk, Rachelle Cipriani, Nicole Lingen, Mark W. Pearson, Alexander T. Seiwert, Tanguy Y. Haraf, Daniel J. affil: Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois sug: subj: Neoadjuvant Therapy Nivolumab Therapeutic Use Chemotherapy, Cancer Human Papillomavirus Viruses Oropharyngeal Neoplasms Drug Therapy Human Progression-Free Survival Overall Survival Confidence Intervals Male Female Quality of Life Programmed Cell Death Ligand 1 Radiotherapy, Conformal Descriptive Statistics Kaplan-Meier Estimator Data Analysis Software Male Female ab: Key Points: Question: Is neoadjuvant nivolumab with chemotherapy followed by response-adapted locoregional therapy effective and well tolerated in patients with human papillomavirus−positive oropharyngeal carcinoma (HPV+ OPC)? Findings: This phase 2 nonrandomized controlled trial of 73 patients with locoregionally advanced HPV+ OPC who were treated with neoadjuvant nivolumab-based therapy demonstrated a deep response (≥50% tumor shrinkage) in 70.8% of the evaluable participants. This response led to reduced local treatment for 86.0% of participants, excellent 2-year survival, and improved functional outcomes; moreover, the expression of programmed death-ligand 1 and clearance of circulating tumor HPV-DNA were associated with improved progression-free survival. Meaning: These findings demonstrate that neoadjuvant nivolumab with chemotherapy followed by response-adaptive treatment can provide excellent overall survival and functional outcomes, including in patients with high-risk HPV+ OPC. 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 This phase 2 nonrandomized controlled trial evaluates effectiveness and tolerance of neoadjuvant nivolumab, nab-paclitaxel, and carboplatin followed by response-adaptive therapy in patients with human papillomavirus−positive oropharyngeal cancer. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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