A Phase II Trial of Camrelizumab in Combination with Concurrent Chemoradiotherapy as First-Line Treatment for Betel Nut-Related Locally Advanced Oral Squamous Cell Carcinoma

Abstract

Purpose/Objective(s)

Betel nut chewing is an established cause of oral cancer. We hypothesized that patients with nonoperative betel nut-related locally advanced oral squamous cell carcinoma (LAOSCC) can benefit from the addition of concurrent and adjuvant camrelizumab to cisplatin-based concurrent chemoradiotherapy (CCRT) as first-line treatment. The purpose of this single arm, phase 2 trial was to evaluate the efficacy and safety of CCRT plus concurrent and adjuvant camrelizumab as first-line treatment for patients with nonoperative betel nut-related LAOSCC.

Materials/Methods

This study was an open-label, single-arm phase 2 trial. A total of 60 patients with betel nut-related (consumption of at least 10 betel nuts per day for more than 5 years), nonoperative, stage III to IVB oral squamous cell carcinoma (OSCC) were enrolled. All patient were treated with CCRT plus concurrent and adjuvant camrelizumab as first-line treatment. The concurrent head and neck irradiation using intensity-modulated radiation therapy (IMRT) was administered at a dose of 70 Gy in 35 fractions. Cisplatin was administered at a dosage of 100mg /m² Q3W, concurrently with radiotherapy. Camrelizumab (200 mg on days 1, 22, and 43) was given concurrently to CCRT, and this was followed by adjuvant doses of 200 mg every 3-weeks for 1 year or until disease progression, the occurrence of unacceptable adverse events (AEs), withdrawal of consent or investigator’s decision. The primary endpoint was disease-free survival (DFS). Secondary outcomes were treatment response, overall survival (OS), local recurrence-free survival (LRFS), local regional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and treatment-related toxicity. This trial is registered with chictr.org.cn (ChiCTR2200056298).

Results

Median follow-up duration was 12 months. The objective response rate (ORR), complete response (CR) rate and partial response (PR) rate were 100%, 88.3%, and 11.7%, respectively. The 1-year DFS, OS, LRFS, LRRFS, and DMFS were 86.7%, 95.0%, 91.7%, 88.3%, and 86.7%, respectively. Compared to patients with a PD-L1 combined positive score (CPS) of < 1, those with a CPS ≥1 have significant higher CR rate (94.1% vs 55.5%, P = 0.001), DFS (92.2% vs 55.5%, P = 0.003), and OS (98.0% vs 77.8%, P = 0.011). The common (incidence ≥ 10%) severe (≥ grade 3) toxic effects included oral mucositis (65.0%), decreased lymphocyte count (36.6%), dysphagia (23.3%), nausea (16.6%), hyponatremia (13.3%), weight loss (11.6%), vomiting (11.6%), and radiation dermatitis (10.0%). The incidence of reactive capillary endothelial proliferation (RCEP) was 6.7%, all of which are grades 1-2. No grade 5 toxicities were observed.

Conclusion

Cisplatin-based concurrent chemoradiotherapy plus concurrent and adjuvant camrelizumab as first-line treatment has demonstrated significant efficacy in patients with nonoperative betel nut-related locally advanced oral squamous cell carcinoma, with tolerable toxicity profiles.