Phase II trial of adjuvant de-escalated radiation + adjuvant nivolumab for intermediate-high risk P16+ oropharynx cancer.

Abstract

6014 Background: Treatment de-intensification for resected, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is an area of active investigation, with a goal of providing a less toxic adjuvant regimen compared to the current standard of care 66 Gy of radiation (RT) combined with concurrent cisplatin defined in recently reported as Arm D of the ECOG3311 trial. Here, the programmed death 1 (PD-1) antibody nivolumab was added to de-intensified RT in high risk, resected HPV+ OPC. Methods: Eligible patients included transorally resected pathologic stage III or IVA HPV+ OPSCC using p16 immunohistochemistry, featuring high-risk neck disease factors (gross extracapsular extension >1mm or ≥5 positive lymph nodes) to mirror ECOG3311 Arm D patients accrued. Positive margin status was excluded except by PI approval. Postoperative treatment consisted of accelerated fractionation RT (50 Gy over 4 weeks) concurrent with nivolumab at 240 mg every 2 weeks, followed by 6 months of adjuvant nivolumab biweekly or monthly. The primary endpoint was progression-free survival (PFS). Swallowing and quality of life patient reported outcome (PRO) measures were collected at baseline and defined intervals after treatment. Results: Forty-one patients (n=41) were accrued and were analyzed. Forty of 41 patients remain alive with a median follow-up of 30 months (range 1 – 49 months). The probability of 3-year overall survival is 97% (95% CI = 90% - 100%) and the probability of 3-year PFS is 86% (95% CI = 68% - 100%). Two patients developed recurrent disease, one of whom died. One patient developed isolated metastasis while a second developed local, regional, and distant metastasis. The most common adverse grade ≥3 adverse events were lymphocytopenia (n=24), dysphagia (n=2) and oral mucositis (n=2). One grade 4 sepsis/multi-organ failure was reported. Comparison of PRO results with those observed in ECOG3311 trial are underway and will be reported. Conclusions: De-intensification of adjuvant treatment adding nivolumab to RT is tolerable and demonstrates favorable clinical outcome for high-risk, resected, HPV+ HNSCC patients. Further targeted immunotherapy combinations are warranted. Clinical trial information: NCT03715946 .