Camrelizumab in combination with apatinib as second-line treatment for advanced esophageal squamous cell carcinoma: A single-arm, open-label, phase II study.
Authors: Wang Feng , Wang Junsheng , Wu Tao , Hong Yonggui , Meng Xiangrui , Ren Zhonghai , Guo Yanzhen , Yang Xiuli , Shi Pei , Yang Jiamei , Fan Qingxia 
Published: January 2021

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Background: Esophageal squamous cell carcinoma (ESCC) is a lethal cancer with a high unmet medical need. Camrelizumab, an anti-PD-1 monoclonal antibody, significantly improved overall survival (OS) and objective response rate (ORR) in Chinese patients (pts) with advanced ESCC compared with chemotherapy, with a manageable safety profile in phase III randomized trial (ESCORT). However, the absolute long-term survival benefiting from PD-1 inhibitors is limited, and new effective treatments are needed. Here, our study aimed to assess the efficacy and safety of combination with camrelizumab and apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC. Methods: This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg intravenous camrelizumab every two weeks plus 250 mg oral apatinib daily in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results: At data cutoff (Sept 11, 2020), 36 pts were enrolled, 7 females and 29 males, and 25 pts had lymph node metastases. Twelve pts received radiotherapy and 25 underwent surgery. Twenty-five pts were included in the efficacy analysis with median follow-up time of 5.0 months and 36 pts in the safety analysis with median follow-up time of 4.6 months. The primary endpoint ORR without confirmation was 40 % with complete response in two pts (8%) and partial response in eight pts (32%). Thirteen pts (52%) had stable disease, and the DCR was 92%. The median PFS and OS were not reached. A total of 72.2% of pts had AEs, and 30.6% of pts experienced grade 3 AEs. The most common AEs (all grade, grade≥3) were elevated aspartate aminotransferase (30.6%, 19.4%), elevated alanine aminotransferase (30.6%, 13.9%), hypertension (25%, 2.8%),neutrophil (25%, 5.6%), thrombocytopenia (25%, 0%), leukopenia (22.2%, 2.8%), anemia (11.1%, 0%), proteinuria (11.1%, 0%), hematochezia (8.3%, 0%), reactive cutaneous capillary endothelial proliferation (5.6%, 2.8%), pruritus (5.6%, 0%), esophageal fistula (5.6%, 0%), fatigue (2.8%, 0%) and hypothyroidism (2.8%, 0%). Conclusions: This is the first study to explore the combination of PD-1 inhibitor and anti-angiogenesis inhibitor as a second-line treatment for advanced ESCC. Camrelizumab plus apatinib demonstrated encouraging clinical efficacy and acceptable safety as second-line treatment, and might be a favorable option for pts with advanced ESCC. Further phase III randomized trials are warranted. Clinical trial information: NCT03736863.