Nivolumab, nabpaclitaxel, and carboplatin followed by risk/response adaptive de-escalated locoregional therapy for HPV-associated oropharyngeal cancer: OPTIMA II trial.
Authors: Ari Rosenberg, Nishant Agrawal, Alexander T. Pearson, Tanguy Y. Seiwert, Zhen Gooi, Elizabeth A. Blair, Daniel Ginat, Adam Howard, Jeffrey Chin, Sara Kochanny, Evgeny Izumchenko, Aditya Juloori, Daniel J. Haraf, Everett E. Vokes
Journal: Journal of Clinical Oncology (2021)

6011 Background: Despite the success of anti-PD-1 in recurrent/metastatic head and neck cancer, incorporation in the curative setting with induction therapy has yet to be investigated. Favorable prognosis of human papillomavirus associated (HPV+) oropharyngeal cancer (OPC) has led to interest in treatment de-escalation. OPTIMA 2 evaluated nivolumab (nivo) with nab-paclitaxel and carboplatin followed by risk/response adaptive de-intensified treatment for locoregionally advanced HPV+ OPC. We report the primary analysis and outcomes. Methods: OPTIMA 2 enrolled locoregionally advanced HPV+ OPC. Nivo, nab-paclitaxel, and carboplatin were administered for 3 cycles. High-risk (HR) included any of the following: T4, N2c-N3 (AJCC 7 th edition), &gt; 20 pack year smoking history, non-HPV16 subtype; All others were low-risk (LR). Arm A included LR with ≥50% post-induction shrinkage by RECIST received single-modality de-escalation with low-dose radiation (RT) alone (50 Gy) or transoral robotic surgery (TORS). Arm B included HR with ≥50% shrinkage or LR with &lt;50% received intermediate-dose chemoradiation (CRT) to 45-50Gy. Arm C included all others and received regular dose CRT to 70-75Gy. Adjuvant nivo was administered for 6 months. The primary endpoint was deep response rate (DRR) ≥50% shrinkage to induction therapy. Results: From September 2017 until March 2020, 73 patients (pts) were eligible and started treatment. One pt died during induction. The DRR following induction was 70.8% (95% CI 60.3%, 81.3%). Median follow-up 23.1 months. Median age 61 (range 39-85), T4 12.3%, N2c/N3 19.2%, LR 47.9%, and HR 52.1%. De-escalated treatment was administered in 84.9%. Arm A N = 28, Arm B N = 34, and Arm C N = 10. 2-year progression free survival (PFS) for full cohort was 90.4% (95% CI = 79.3%, 95.7%). 2-year PFS for Arms A, B, and C were 96.3%, 85.8%, and 100.0% respectively. 2-year overall survival (OS) for full cohort was 93.3% (95% CI = 82.4%, 97.5%). 2-year OS for Arm A, B, and C were 96.0%, 91.9%, and 100.0% respectively. Among TORS (N = 9), pathologic complete response (pCR) rate was 66.7%. G-tube rates in Arms A, B, and C were 7.1%, 44.1%, and 75.0% respectively (p = 0.0001). Grade 4 toxicity in arms A, B, and C, were observed in 7.1%, 8.8%, and 10.0% of pts respectively. There were 3 local failures and no distant failures. Conclusions: Nivo/nab-paclitaxel/carboplatin followed by risk/response adaptive de-escalated treatment in locoregionally advanced HPV+ OPC demonstrates excellent survival outcomes with reduced toxicity and enteral feeding rates, including high risk disease. Induction chemoimmunotherapy demonstrates a high rate of deep clinical response and represents a promising de-escalation approach that incorporates anti-PD1 in the definitive setting. High pCR rate was observed following nivo/nab-paclitaxel/carboplatin. Clinical trial information: NCT03107182.