The expression of programmed death ligand-1 (PD-L1) and use of PD-1 inhibitor-directed therapy with nivolomab in oral cavity cancer arising from recreational use of areca nut.

Abstract

e17504 Background: Oral cavity cancer (OCC) caused by the carcinogen arecoline from recreational use of areca nut (AN), i.e. betel nut chewing is one of the most prevalent cancers in SE Asia and India where it accounts for up to 30% of all cancer. In contrast, OCC in the West due to tobacco and alcohol accounts for 90% of cases, and HPV the rest. In the US, immunotherapy utilizing anti-PD-1 therapy yielded a 24.8% response rate (RR) against head & neck cancer (HNC) with 50% RR for high PD-L1 expression, while HPV+ disease has even odds of responding to this approach. Thus far, no studies have focused on whether anti-PD-1 immunotherapy is effective in AN-derived OCC or if PD-L1 expression occurs in these cancers. The, the use of nivolomab in a patient with PD-L1 positive (+) OCC caused by AN is presented. Methods: A 45-yo, Chuukese man non-smoker and user of AN presented with massive, locally recurrent cancer originating from P16 negative, squamous cell carcinoma of the gum. The disease was treated with radical surgery, chemoradiotherapy, cetuximab-chemotherapy, and salvage chemotherapy. After 2 years, progressive disease replaced the floor of the mouth and a majority of the left face and neck. A tracheostomy was needed due to airway obstruction. His cancer tested PD-L1 3+ 80% + (Cell Signaling Co., E1L3N) and PD-1 negative (CellMarque Co., MRQ-22). Nivolomab 3 mg/kg q2w was obtained through a patient access program at BMS. Results: The patient achieved a 90% regression of cancer. The disappearance of cancer was interpreted by a radiologist, “the facial tumor seen on the previous CT scan appears to have been surgically removed.” A portion of the facial tumor sloughed and was evaluated histologically showing a necroinflammatory infiltrate with abundant residual keratin and no cancer. The response lasted 3 months before a mixed response ensued. No autoimmune toxicities were encountered. Conclusions: OCC caused by AN appears similar to other HNC in the expression PD-L1 and response to anti-PD-1 directed immunotherapy. The high prevalence of OCC in India and SE Asia provides a unique opportunity for investigating the optimal use of this immune strategy.