Gastric cancer is frequently diagnosed at the advanced stage when treatment options are limited to local treatment, chemotherapy, or targeted therapy. However, treatment at this stage typically does not convey improvement in survival outcomes. Immunotherapy is being actively explored as a treatment option for patients with advanced gastric cancer, with nivolumab and pembrolizumab being recently approved for third-line treatment in Japan and the United States. Sintilimab, a monoclonal antibody, is a programmed cell death protein 1 inhibitor that is undergoing clinical trials as a treatment option for a variety of cancer types, including treatment as a second-line or above therapy for patients with advanced or metastatic gastric cancer.
In a clinical trial in China, 52 patients with previously treated advanced or metastatic gastric cancer were enrolled in a trial to study sintilimab monotherapy (n = 8) or combination therapy (n = 44) with either chemotherapy or targeted therapy. The trial included 23 patients with advanced gastric cancer and 29 patients with gastroesophageal junction adenocarcinoma. The study’s primary end point was progression-free survival (PFS), with secondary study end points of overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Sintilimab 200 mg was administered intravenously once every 3 weeks. To evaluate treatment response, imaging was performed on all patients every 2 weeks. Response rate evaluation found that 8 patients had a partial response to therapy, progressive disease occurred in 18 patients, and 26 patients had stable disease. Overall ORR was 15.4% and DCR was 65.2%.
The investigators also evaluated responses by intestinal subtype and found 10 patients with stable disease, 6 patients with partial response, and 4 patients with progressive disease. Along with these responses, the intestinal subtype group had an ORR of 30.0% and a DCR of 80.0%. For patients with a nonintestinal subtype, the ORR was 6.3%, the DCR was 56.3%, OS was 4.1 months, and PFS was 1.9 months. The median PFS was 2.5 months with a median PFS of 1.5 months in the monotherapy group and 2.9 months in the combination therapy group. The median OS was 5.8 months; for the monotherapy group median OS was 4.0 months and for the combination group OS was 6.0 months.
All patients reported experiencing ≥1 treatment-related adverse events, with 2 patients discontinuing treatment due to adverse events and a 44.2% rate of grade 3/4 adverse events. The most frequently reported adverse events were a decrease in neutrophil counts, decreased platelets, anemia, and a decrease in white blood cell count.
The use of sintilimab in patients with previously treated advanced or metastatic gastric cancer demonstrated a modest response and was well-tolerated.
Nie C, Lv H, Liu Y, et al. Clinical study of sintilimab as second-line or above therapy in patients with advanced or metastatic gastric cancer: a retrospective study. Front Oncol. 2021;11:741865.