Potential of Sintilimab Plus Apatinib and Chemotherapy in Gastric or Gastroesophageal Junction Cancer

According to a phase 2 trial, sintilimab plus apatinib and chemotherapy demonstrated anti-tumor activity and tolerable safety among patients with gastric or gastroesophageal junction (GEJ) cancer.

Past studies have shown “the efficacy of single-agent PD-1 monoclonal antibody was limited,” wrote Le Zhang, MD, National Clinical Research Center for Cancer, Tianjin, China and coauthors, though “a synergistic effect of PH-1/PH-L1 antibody plus chemotherapy or VEGFR2 inhibitor” has been demonstrated. These data were the basis for this trial evaluating a combination of chemotherapy, the PD-1 antibody sintilimab, and the VEGFR2 inhibitor apatinib.

This prospective, single-arm trial enrolled 30 previously treated patients with advanced gastric or GEJ adenocarcinoma at Tianjin Medical University Center and Hospital between May 2019 and May 2021. All patients received the investigator’s choice of chemotherapy (specific dose level intravenous paclitaxel of irinotecan), 200 mg sintilimab on day 1, and 250 mg apatinib once daily continuously, until disease progression, intolerability, or withdrawal of consent. The primary end points of this trial were objective response rate and progression free survival. The main secondary end points were overall survival, disease control rate, and safety.

Of the 30 patients enrolled, 28 were evaluable for efficacy. With a median follow-up duration of 12.3 months, the objective response rate was 53.6% and the disease control rate was 82.1% (partial response, n = 15; stable disease, n = 8). The median progression-free survival was 8.5 months, and the median overall survival was 12.5 months. Multivariate analysis found liver metastasis was an independent prognostic factor for both progression-free survival (hazard ratio, 0.208; 95% confidence interval, .044 to .988; P = .048) and overall survival (HR, 0.214; 95% CI, 0.049 to 0.947; P = .042).

Grade 3/4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia, and proteinuria. The most common grade 3/4 adverse events were neutropenia, in 13.3% of patients, and leukopenia in 6.7%. 

The limitations of this study include the small, single-arm design and the study population containing only HER2-negative and mismatch repair proficient patients.

Dr Zhang, et al, concluded “these results indicate a significant improvement over previous second-line treatments, suggesting that the combination of a PD-1 inhibitor, VEGFR inhibitor, and chemotherapy has a certain synergistic effect,” and added, “the regiment was well-tolerated and deserves further research.”

Source:

Zhang L, Wang W, Ge S, et al. Sintilimab plus apatinib and chemotherapy as second-/third-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma: A prospective single-arm, phase II trial. BMC Cancer. 2023; 23(211). doi:10.1186/s12885-023-10661-4