Camrelizumab in combination with apatinib demonstrated encouraging clinical efficacy as a second-line treatment of patients with esophageal squamous cell carcinoma and demonstrated acceptable safety in a single-arm, open-label phase 2 clinical trial.
Camrelizumab (SHR-1210) in combination with apatinib (Rivoceranib) demonstrated encouraging clinical efficacy as a second-line treatment of patients with esophageal squamous cell carcinoma (ESCC) and demonstrated acceptable safety in a single-arm, open-label phase 2 clinical trial presented during the 2021 Gastrointestinal (GI) Cancers Symposium.
This study (NCT03736863) was the first to explore the combination of a PD-1 inhibitor with an anti-angiogenesis inhibitor as the second-line treatment for patients with advanced ESCC.
The anti–PD-1 monoclonal antibody camrelizumab induced significant improvements in overall survival (OS) and objective response rate (ORR) compared with chemotherapy in the randomized phase 3 ESCORT study of Chinese patients with advanced ESCC, but the absolute long-term survival benefit from PD-1 inhibitors remains limited. New treatment options that are effective in this patient population are needed, which led to the rationale for this study. The trial aimed to evaluate the safety and efficacy of camrelizumab in combination with the VEGFR2 inhibitor apatinib in the second-line setting.
The trial, which remains ongoing, is enrolling patients with unresectable locally advanced, locally recurrent, or metastatic ESCC across China. To be included in the study, patients must have an ECOG performance status of 0 or 1, be aged 18 to 75 years, and have progressed on or were intolerant to frontline chemotherapy. Camrelizumab was administered at 200 mg intravenously every 2 weeks, and apatinib was given at 250 mg orally daily in 4-week cycles. The primary end point is investigator-assessed ORR, and secondary end points include OS, progression-free survival (PFS), and disease control rate (DCR).
With a data cutoff date of November 16, 2020, a total of 46 patients had been enrolled from 9 sites and all were included in the full analysis set, as well as the safety analysis set. Thirty patients were evaluated in the per-protocol analysis set. The majority of patients were male (n = 38) and had an ECOG performance status of 1 (n = 34). The median age was 63 (range, 48-72) and metastatic sites included lymph nodes in 35 patients, lung in 9, and liver in 8. Forty-six patients had undergone prior chemotherapy, 33 had undergone surgery, and 17 received radiotherapy.
The ORR among 30 evaluable patients was 43.3%, with 4 patients achieving a complete response (CR) with camrelizumab, 9 achieving a partial response (PR), and 15 reaching stable disease (SD). After confirmation, 3 patients had a CR and 7 had a PR for an ORR of 33.3%. Patients who had a response to treatment demonstrated better tumor shrinkage than those who did not respond. The DCR was 93.3%.
The median PFS was 4.07 months with the combination (95% CI, 3.75-not available). The median 3-month OS rate was 82.2%, the 6-month rate was 67.6%, and the 9-month OS rate was 61.5%.
Overall, 33 patients (71.7%) experienced treatment-emergent adverse events (TEAEs), and these events were grade 3 or higher in 23 patients. The most common grade 3 or higher TEAEs included elevated aspartate aminotransferase in 7 patients (15.2%), elevated alanine transaminase in 5 (10.9%), elevated glutamyltransferase in 4 (8.7%), hemorrhage in 3 (6.5%), and increased total bilirubin, increased direct bilirubin, and esophageal fistula in 2 patients each (4.4%).
Eleven patients temporarily discontinued treatment or had a reduced dose of camrelizumab due to TEAEs.
In terms of any-grade immune-related AEs, 4 patients (8.7%) had thyroid function abnormalities, 2 (4.3%) had reactive capillary endothelial proliferation (RCEP), and 1 (2.2%) had pneumonitis. The only grade 3 or higher immune-related event was RCEP, which occurred in 1 patient (2.2%).
Patients received treatment until disease progression, unacceptable toxicity, patient withdrawal from the study, or investigator decision. Tumor response was evaluated every 2 cycles for the first 12 cycles of treatment, and then every 3 cycles thereafter by RECIST 1.1. AEs were assessed continuously for up to 90 days following the last dose of treatment.
Further randomized phase 3 clinical trials are warranted to further understand the efficacy and safety of camrelizumab plus apatinib in this patient population.
Wang F, Wang J, Wu T, et al. Camrelizumab in combination with apatinib as second-line treatment for advanced esophageal squamous cell carcinoma: A single-arm, open-label, phase II study. J Clin Oncol.2021;39(suppl 3):215.