Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first‐line treatment of advanced esophageal squamous cell carcinoma

BACKGROUND: Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma (ESCC). The incorporation of an immune checkpoint inhibitor and a molecular anti‐angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects. Therefore, we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first‐line treatment of advanced ESCC. METHODS: In this single‐arm prospective phase II trial, patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg, liposomal paclitaxel 150 mg/m(2), and nedaplatin 50 mg/m(2) on day 1, and apatinib 250 mg on days 1‐14. The treatments were repeated every 14 days for up to 9 cycles, followed by maintenance therapy with camrelizumab and apatinib. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Secondary endpoints included disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. RESULTS: We enrolled 30 patients between August 7, 2018 and February 23, 2019. The median follow‐up was 24.98 months (95% confidence interval [CI]: 23.05‐26.16 months). The centrally assessed ORR was 80.0% (95% CI: 61.4%‐92.3%), with a median duration of response of 9.77 months (range: 1.54 to 24.82+ months). The DCR reached 96.7% (95% CI: 82.8%‐99.9%). The median PFS was 6.85 months (95% CI: 4.46‐14.20 months), and the median OS was 19.43 months (95% CI: 9.93 months – not reached). The most common grade 3‐4 treatment‐related adverse events (AEs) were leukopenia (83.3%), neutropenia (60.0%), and increased aspartate aminotransferase level (26.7%). Treatment‐related serious AEs included febrile neutropenia, leukopenia, and anorexia in one patient (3.3%), and single cases of increased blood bilirubin level (3.3%) and toxic epidermal necrolysis (3.3%). No treatment‐related deaths occurred. CONCLUSIONS: Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first‐line treatment demonstrated feasible anti‐tumor activity and manageable safety in patients with advanced ESCC. Randomized trials to evaluate this new combination strategy are warranted. TRIAL REGISTRATION: This trial was registered on July 27, 2018, at ClinicalTrials.gov (identifier: NCT03603756).