Conversion therapy with sintilimab combined with chemotherapy and apatinib in stage IV gastric cancer.

In selected patients with stage IV gastric cancer, radical surgery after conversion therapy may increase survival benefit; however, there is currently no standard protocol for conversion therapy. We explored the feasibility and efficacy of sintilimab plus two-drug chemotherapy (S-1 plus nab-paclitaxel) and apatinib as conversion therapy in patients with stage IV gastric cancer in China. This was a prospective, single-arm, single-center, phase 2 study. The primary endpoint was the R0 conversion rate, defined as the proportion of R0 surgical patients to the total number of patients treated. Of 56 patients screened, 47 were enrolled, received preoperative treatment, and were evaluated for tumor response. Most patients (28/47; 59.6%) had two or three unresectable factors. The objective response rate and disease control rate were 53.2% and 97.9%, respectively. Of the 46/47 patients who achieved disease control, 35 underwent surgery. The R0 conversion rate was 51.1% (24/47). A pathological complete response was observed in 14.3% (5/35) of patients. Median overall survival and event-free survival were 25.7 and 15.3 months, respectively. Overall survival and event-free survival were significantly better in surgical patients compared with non-surgical patients (p < 0.001). In the surgical population, R1/R2 resection was the only significant independent predictor of unfavorable event-free survival by multivariate analysis (p = 0.015). There were no chemotherapy- or perioperative-related deaths. The safety profile was manageable. Sintilimab plus chemotherapy and apatinib followed by conversional resection may be a new feasible and safe option for initially unresectable gastric cancer, potentially leading to long-term survival or even cure.