Efficacy and safety of camrelizumab and apatinib combined with induction chemotherapy and concurrent chemoradiotherapy for stage T <sub>any</sub> N3M0 nasopharyngeal carcinoma: A phase II QUINTUPLED trial.
Authors: Hu Liang, Lin Wang, Nian Lu, Yao-Fei Jiang, Jian-Wei Wang, Wei-Xin Bei, Liang-Ru Ke, Yan-Fang Ye, Guo-Ying Liu, Wang-Zhong Li, LiTing Liu, Jin-Ling Duan, Chong Zhao, Weixiong Xia, Xiang Yanqun
Journal: Journal of Clinical Oncology (2022)

6012 Background: Prognosis of nasopharyngeal carcinoma (NPC) with stage T any N3M0 remains unsatisfactory due to high-risk of distant metastasis, indicating the need of more comprehensive treatment strategy. Synergistic effects are observed when immune checkpoint blockade anti-PD-1 is combined with chemotherapy or anti-angiogenic agents. This trial investigated the efficacy and safety of anti-PD-1 camrelizumab and anti-angiogenic agent apatinib in combination with induction chemotherapy and concurrent chemoradiotherapy (CCRT) in patients with T any N3M0 NPC. Methods: In this phase II trial, patients with T any N3M0 NPC (AJCC 8 th edition) were enrolled and treated with induction chemotherapy (NAB-paclitaxel, 200 mg/m 2 , day 1; cisplatin 60 mg/m 2 , day 1; and capecitabine, 1000 mg/m 2 , orally twice a day, days 1-14; every 21-day for 3 cycles) and apatinib (250 mg, 5 days/week, for up to 8 weeks), followed by CCRT (cisplatin, 100 mg/m 2 , day 1, every 21-day for 2 cycles and IMRT). Camrelizumab (200 mg once every 3 weeks) was given from the first cycle of induction chemotherapy until one year. Prescribed radiation doses were 68-72 Gy, 64-68 Gy, 60-64 Gy, and 54-58 Gy in 30-33 fractions for PTVnx, PTVnd, PTV high-risk , and PTV low-risk , respectively. Primary endpoint was 1-year distant metastasis-free survival (DMFS). Patient’s response to the therapy was evaluated using RECIST 1.1. Results: From May 2020 to July 2021, 50 eligible patients were enrolled. Median age was 45 years (range 20-65), median EBV DNA concentration was 4520 copy/ml (IQR 1595-17550), and 13 patients (26%) were female. Among 50 patients evaluable for response assessment after induction therapy, all patients had overall response, including 12 patients (24%) with complete response (CR). After 1-3 cycles of induction therapy, 84.8% (28/33 available) patients achieved negative pathological finding in the primary tumor site from endoscopic biopsy and 50% (17/34 available) from lymph nodes biopsy. Except one patient achieved regional partial response and one patient died from liver and bone metastases, the other patients all achieved CR at 3 months after radiotherapy. One-year DMFS rate was 98% (95% CI 96-100) with a median follow-up of 12.3 months (range 6.4-20.2). Grade ≥3 toxicity appeared in 32 (64%) of 50 patients and mainly consisted of nausea/vomiting (9 [18%]), neutropenia (8 [16%]), leukopenia (7 [14%]), anemia (7 [14%]), rash (5 [10%]) and thrombocytopenia (5 [10%]). Safety profile was anticipated without treatment or immune-related deaths. Conclusions: Camrelizumab and apatinib combined with induction chemotherapy of NAB-paclitaxel, cisplatin and capecitabine and CCRT shows excellent distant metastatic control with acceptable safety, which is a new promising and effective systemic therapy regimen for high-risk of metastatic NPC patients. Clinical trial information: ChiCTR2000032317.