Although FLOT has been recognized as the first choice for neoadjuvant chemotherapy in gastric or GEJ adenocarcinoma, its efficacy needs to be improved. Sintilimab, a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. We aimed to assess the activity and safety profile of the combination of FLOT and sintilimab for neoadjuvant treatment of gastric or GEJ adenocarcinoma.
In this ongoing, single-arm, phase II study, we recruited patients from Henan Cancer Hospital in China with histopathologically diagnosed resectable gastric or GEJ adenocarcinoma who had clinical T3/N+ or higher stage. Patients were given 4 cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 80 mg/m2, leucovorin 200 mg/m2, fluorouracil 2600 mg/m2, 24-h infusion on day 1, q2w) in combination with 3 cycles of sintilimab (200mg, iv, d1, q3w), followed by surgery and 4 postoperative cycles of FLOT. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR).
Between Aug 10, 2019, and Jul 15, 2020, 19 patients were enrolled and commenced treatment. The grade 3 or 4 treatment-related adverse events (TRAE) included diarrhea (10.5%), leukopenia (5.3%), neutropenia (5.3%), anaemia (10.5%). Most frequent grade 1 or 2 TRAE were leukopenia (42.1%), neutropenia (31.6%) and Glutamic-pyruvate transaminase increased (42.1%). A total of 17 patients (89.4%) were eligible for efficacy assessment, and among 9 patients who experienced D2 resection, 6 (66.7%) achieved MPR, including 2 (22.2%) with pCR. According to RECIST v1.1, 6 of 17 patients (35.3%) achieved partial response (PR), and 11 of 17 patients (64.7%) achieved stable disease (SD). The ORR and disease control rate (DCR) for 17 patients were 35.3% and 100%, respectively.
Neoadjuvant combination of sintilimab and FOLT is a safe and efficacious treatment option for patients with gastric or GEJ adenocarcinoma, and 22.2% pCR rate is encouraging. Our clinical study (NCT04341857) is still enrolling, and the survival effects are under follow up.
The authors.
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All authors have declared no conflicts of interest.