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

person Heath Devin Skinner UPMC Hillman Cancer Center, Department of Radiation Oncology, Pittsburgh, PA info_outline Heath Devin Skinner, Dan Paul Zandberg, Adam Raben, Shaum Sridharan, Mark Kubik, Jose Zevallos, Seungwon Kim, Umamaheswar Duvvuri, James Ohr, William E. Gooding, Robert L. Ferris

Authors person Heath Devin Skinner UPMC Hillman Cancer Center, Department of Radiation Oncology, Pittsburgh, PA info_outline Heath Devin Skinner, Dan Paul Zandberg, Adam Raben, Shaum Sridharan, Mark Kubik, Jose Zevallos, Seungwon Kim, Umamaheswar Duvvuri, James Ohr, William E. Gooding, Robert L. Ferris Organizations UPMC Hillman Cancer Center, Department of Radiation Oncology, Pittsburgh, PA, UPMC Hillman Cancer Center, Pittsburgh, PA, Helen F. Graham Cancer Center and Research Institute, Newark, DE, University of Pittsburgh Department of Otolaryngology, Pittsburgh, PA, University of Pittsburgh Medical Center, Pittsburgh, PA, University of Pittsburgh School of Medicine, Pittsburgh, PA, University of Pittsburgh Cancer Institute, Pittsburgh, PA Abstract Disclosures Research Funding U.S. National Institutes of Health U.S. National Institutes of Health 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.

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