Immune checkpoint inhibitors have greatly improved the prognoses of diverse advanced
malignancies, including gastric and gastroesophageal junction (G/GEJ)
cancer. However, the role of anti-programmed cell death protein-1 treatment in the neoadjuvant setting remains unclear. This phase 2 study aimed to evaluate
sintilimab plus CapeOx as a neoadjuvant regimen in patients with advanced resectable G/GEJ
adenocarcinoma. Eligible patients with resectable G/GEJ
adenocarcinoma stage cT3-4NanyM0 were enrolled. Patients received
neoadjuvant treatment with
sintilimab (3 mg/kg for cases <60 kg or 200 mg for those ≥60 kg on day 1) plus CapeOx (
oxaliplatin at 130 mg/m2 on D1 and
capecitabine at 1000 mg/m2 two times per day on D1-D14) every 21 days, for three cycles before surgical resection, followed by adjuvant treatment with three cycles of CapeOx with the same dosages after surgical resection. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included objective response rate,
tumor regression grade per Becker criteria, survival and safety. As of July 30, 2020, 36 patients were enrolled. Totally 7 (19.4%) patients had GEJ
cancer, and 34 (94.4%) patients were clinical stage III cases. A total of 35 (97.2%) patients completed three cycles of
neoadjuvant treatment, and 1 patients received two cycles due to adverse events. All patients underwent surgery and the R0 resection rate was 97.2%. In this study, pCR and major pathological response were achieved in 7 (19.4%, 95% CI: 8.8% to 35.7%; 90% CI: 10.7% to 33.1%) and 17 (47.2%, 95% CI: 31.6% to 64.3%) patients, respectively. Thirty-one patients received adjuvant treatment. By December 20, 2021, three patients died after disease relapse, and two patients were alive with relapse. Median disease-free survival (DFS) and overall survival (OS) were not reached. The 1-year DFS and OS rates were 90.3% (95% CI: 80.4% to 100.0%) and 94.1% (95% CI: 86.5% to 100.0%), respectively. The most common (>1 patient) grade 3 treatment-related adverse events during
neoadjuvant treatment were
anemia and
neutropenia (n=5 each, 13.9%). No serious adverse events (AEs) or grade 4-5 AEs were observed.
Sintilimab plus
oxaliplatin/
capecitabine showed promising efficacy with encouraging pCR rate and good safety profile in the neoadjuvant setting. This combination regimen might present a new option for patients with locally advanced, resectable G/GEJ
adenocarcinoma. Trial registration; NCT04065282.