Pathologic Response of Phase III Study: Perioperative Camrelizumab Plus Rivoceranib and Chemotherapy Versus Chemotherapy for Locally Advanced Gastric Cancer (DRAGON IV/CAP 05)

Abstract

Purpose: This multicenter, randomized phase III trial evaluated the efficacy and safety of perioperative camrelizumab (an anti-PD-1 antibody) plus low-dose rivoceranib (a VEGFR-2 inhibitor) and S-1 and oxaliplatin (SOX) (SOXRC), high-dose rivoceranib plus SOX (SOXR), and SOX alone (SOX) for locally advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

Methods: Patients with T3-4aN + M0 G/GEJ adenocarcinoma were randomly assigned (1:1:1) to receive perioperative treatment with SOXRC, SOXR, or SOX. The primary end points were pathologic complete response (pCR) and event-free survival. The Independent Data Monitoring Committee recommended stopping enrollment in the SOXR group on the basis of the safety data of the first 103 randomly assigned patients in the three groups. The patients were then randomly assigned 1:1 to the SOXRC or SOX groups. This report presents the pCR results obtained per protocol for the first 360 randomly assigned patients who had the opportunity for surgery in the SOXRC and SOX groups.

Results: In the SOXRC and SOX groups, of the 180 patients in each group, 99% and 98% of patients received neoadjuvant therapy, 91% and 94% completed planned neoadjuvant therapy, and 86% and 87% underwent surgery, respectively. The pCR was significantly higher in the SOXRC group at 18.3% (95% CI, 13.0 to 24.8) compared with 5.0% (95% CI, 2.3 to 9.3) in the SOX group (difference of 13.7%; 95% CI, 7.2 to 20.1; odds ratio of 4.5 [95% CI, 2.1 to 9.9]). The one-sided P value was <.0001, crossing the prespecified statistical significance threshold of P = .005. Surgical complications and grade ≥3 neoadjuvant treatment-related adverse events were 27% versus 33% and 34% versus 17% for SOXRC and SOX, respectively.

Conclusion: The SOXRC regimen significantly improved pCR compared with SOX alone in patients with G/GEJ adenocarcinoma with a tolerable safety profile.

Trial registration: ClinicalTrials.gov NCT04208347.

FIG 1.

CONSORT diagram. ^aOne patient in the SOX group did not receive the study drugs but underwent D2 radical resection for gastric cancer. SOX, S-1 and oxaliplatin; SOXRC, perioperative low-dose rivoceranib plus camrelizumab and SOX.

FIG 2.

Pathologic complete response in the intention-to-treat population as assessed by the blinded independent review committee. (A) The analysis of pathologic complete response, and the difference between the two groups was calculated using a stratified Cochran-Mantel-Haenszel method. (B) Pathologic complete response in prespecified subgroups on the basis of the baseline characteristics. CPS, combined positive score; dMMR, deficient mismatch repair; EBV, Epstein-Barr virus; ECOG, Eastern Cooperative Oncology Group; GEJ, gastroesophageal junction; MMR, mismatch repair; NA, not available; OR, odds ratio; pCR, pathologic complete response; pMMR, proficient mismatch repair; SOX, S-1 and oxaliplatin; SOXRC, perioperative low-dose rivoceranib plus camrelizumab and SOX.