Induction chemotherapy with or without toripalimab followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicenter, open-label, randomized, controlled, phase 2 trial.

Abstract

6077 Background: Although nasopharyngeal carcinoma (NPC) treatment has entered the era of immunotherapy, the optimal treatment model for locoregionally advanced nasopharyngeal carcinoma (LANPC) remains unclear. This trial aimed to evaluate the efficacy and safety of adding toripalimab to induction chemotherapy (IC) in patients with LANPC. Methods: Patients with LANPC (T4NanyM0 or TanyN2/N3M0, AJCC 8th edition) were enrolled at 8 centers across China and randomized (1:1) into two arms: the standard arm (gemcitabine and cisplatin IC followed by cisplatin concurrent chemoradiotherapy [CCRT]) and the toripalimab arm (toripalimab plus IC followed by CCRT). Both arms received intravenous gemcitabine (1g/m²) on days 1 and 8, and cisplatin (80 mg/m²) on day 1, every 3 weeks for 3 cycles, followed by standard CCRT (cisplatin 100 mg/m² every 3 weeks for 3 cycles). In the toripalimab arm, patients also received intravenous toripalimab (240 mg) on day 1 every 3 weeks for 3 induction cycles. The primary endpoint was failure-free survival (FFS). Secondary endpoints included complete response (CR) rate after neoadjuvant treatment, locoregional failure-free survival (LRRFS), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity. Response evaluation was conducted according to RECIST 1.1, and adverse events (AEs) were assessed by CTCAE v5.0. This study is registered with ClinicalTrials.gov (NCT05340270), and follow-up is ongoing. Results: Between July 2022 and March 2024, 150 patients (mean age 47 years, 72% male) were randomized to the toripalimab arm (n = 75) and the standard arm (n = 75). As of November 30, 2024, the median follow-up duration was 23.4 months, and 15 patients had reached the primary endpoint. Long-term efficacy data are still awaited. The CR rate after neoadjuvant treatment was 36.0% (27 of 75) in the toripalimab arm and 13.3% (10 of 75) in the standard arm ( P = 0.001). The overall response rate (ORR) after neoadjuvant treatment was 94.7% (71 of 75) in the toripalimab arm and 85.3% (64 of 75) in the standard arm ( P = 0.042). Grade 3-4 acute treatment-related adverse events (trAEs) occurred in 50 (66.7%) patients in the toripalimab arm and46 (61.3%) patients in the standard arm ( P = 0.496), with immune-related AEs (irAEs) reported in 5 (6.7%) patients in the toripalimab arm and none (0.0%) in the standard arm ( P = 0.058). All grade 3-4 irAEs were manifested as rashes and pruritus. Conclusions: Adding toripalimab to standard IC followed by CCRT resulted in a superior CR rate and ORR compared to IC-CCRT alone, with manageable toxicity profiles in patients with LANPC. Further follow-up is needed to confirm long-term efficacy, and this combination may offer an optimal, cost-effective therapeutic model for LANPC. Clinical trial information: NCT05340270 .