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Clinical Trial
. 2024 Jul 1;10(7):923-931.
doi: 10.1001/jamaoncol.2024.1530.

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

Ari J Rosenberg  1   2 , Nishant Agrawal  2   3 , Aditya Juloori  2   4 , John Cursio  5 , Zhen Gooi  3 , Elizabeth Blair  2   3 , Jeffrey Chin  1 , Daniel Ginat  2   6 , Olga Pasternak-Wise  2   6 , Rifat Hasina  2   3 , Anna Starus  7 , Frederick S Jones  7 , Evgeny Izumchenko  1   2 , Ellen MacCracken  3 , Rachelle Wolk  2   8 , Nicole Cipriani  2   8 , Mark W Lingen  2   8 , Alexander T Pearson  1   2 , Tanguy Y Seiwert  9 , Daniel J Haraf  2   4 , Everett E Vokes  1   2
Affiliations
Clinical Trial

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

Ari J Rosenberg et al. JAMA Oncol. .

Erratum in

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Rosenberg reported personal fees from EMD Serono, Astellas, Novartis, Vaccitech, Eisai, Nanobiotix, Privo Technologies, and Galectin outside the submitted work. Dr Juloori reported grants from AstraZeneca and personal fees from Isoray, GE, and Aqualung outside the submitted work. Dr Hasina reported grants from the US National Institutes of Health during the conduct of the study. Dr Pearson reported grants and personal fees from AbbVie, grants from Kura, and personal fees from Elevar, Prelude, and Privo Technologies outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram of Study Participants
CRT indicates chemoradiotherapy; TFHX, paclitaxel (100 mg/m2 on day 1), 5-fluorouracil continuous infusion (600 mg/m2/d on days 0-5), and hydroxyurea (500 mg orally twice daily on days 0-5 with 11 doses per cycle).
Figure 2.
Figure 2.. Response to Nivolumab Plus Nab-Paclitaxel and Carboplatin, per RESIST Criteria
aHigh-risk disease. RECIST indicates Response Evaluation Criteria in Solid Tumors, 1.1.
Figure 3.
Figure 3.. Overall Survival and Progression-Free Survival, Overall and by Treatment Group
Figure 4.
Figure 4.. ctHPV-DNA Dynamics and Radiographic Response During Neoadjuvant Therapy
A, Solid lines denote radiographic response to neoadjuvant therapy; dashed lines, patients with persistent ctHPV-DNA at follow-up; and diamonds, residual HPV-DNA data points. B, PFS for patients with detectable vs undetectable ctHPV-DNA after neoadjuvant chemoimmunotherapy. ctHPV-DNA indicates circulating tumor human papillomavirus DNA; and PFS, progression-free survival.
See this image and copyright information in PMC

References

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