Gastric cancer, as one of the most common malignant tumors worldwide, has persistently high incidence and mortality rates. It is highly heterogeneous and invasive. Most patients are diagnosed at an advanced stage with very poor prognosis; the five-year survival rate for advanced gastric cancer patients is less than 10%. However, this year's ASCO annual meeting brings us many new hopes. Let us step into the frontier of gastric cancer research at the 2025 ASCO Annual Meeting to explore those research achievements that bring hope and new life to gastric cancer patients.
At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, the treatment landscape for gastric cancer is undergoing revolutionary breakthroughs. Strategies such as immunotherapy, targeted drugs combined with chemotherapy, and cell therapies continuously push the boundaries of efficacy. From adjuvant/neoadjuvant treatment to advanced systemic therapy, multiple key clinical studies announced significant progress at the 2025 ASCO conference: Camrelizumab combined with chemotherapy significantly improved the objective response rate (ORR 59.18%) and progression-free survival (mPFS 10.03 months) in initially unresectable patients, providing a new path for conversion therapy; Nivolumab adjuvant therapy (CheckMate 577) extended median disease-free survival (mDFS) to 22.4 months, establishing the core role of immunotherapy in perioperative treatment; Pembrolizumab combined with lenvatinib and chemotherapy showed improvements in progression-free survival (PFS) and ORR but failed to reach the primary endpoint of overall survival (OS), leaving its future uncertain; Trastuzumab deruxtecan (DESTINY-Gastric04) demonstrated survival benefits in second-line treatment of HER2-positive gastric cancer for the first time in a phase III trial, rewriting treatment standards; Claudin18.2-targeted CAR-T therapy (CT041) showed a 54.9% ORR in refractory gastric cancer, opening a new era of cell therapy for solid tumors. Overall, the studies highlight the clinical value of precise subtyping and multi-mechanism synergy and provide guidance for optimizing individualized treatment strategies. Below, please follow the editor to review the detailed information.
(Abstract No.: 4016; Qirong Geng)
This is a single-center retrospective observational cohort study including 103 patients, with 49 receiving camrelizumab combined with SOX/CapeOX (camrelizumab group) and 54 receiving SOX/CapeOX only (chemotherapy group). The camrelizumab combined chemotherapy group showed significantly higher ORR and disease control rate (DCR) than the chemotherapy-only group, 59.18% vs 38.89% (P=0.048) and 83.67% vs 62.96% (P=0.018), respectively. Median PFS was significantly longer in the combined therapy group than in the chemotherapy group, 10.03 months vs 6.24 months (HR 0.603, 95% CI: 0.368–0.989, P=0.045). The most common grade 3–4 treatment-related adverse events were neutropenia (57% vs 54%), anemia (39% vs 33%), and thrombocytopenia (39% vs 33%) in the combined vs chemotherapy groups. Reactive cutaneous capillary endothelial proliferation (RCCEP) incidence was higher in the combined group (73% vs 0%) but was limited to grade 1–2. Clinical outcomes in the camrelizumab combined group were superior to chemotherapy alone, and the safety of the combined regimen was manageable.
(Abstract No.: 4000; Ronan Joseph Kelly)
CheckMate-577 is a phase III, randomized, multicenter, double-blind clinical trial evaluating the efficacy and safety of nivolumab in patients with residual pathological disease after neoadjuvant CRT and complete surgical resection of esophageal or gastroesophageal junction cancer. A total of 794 patients were enrolled and randomized 2:1 to nivolumab or placebo for one year of treatment. Median disease-free survival (mDFS) reached 22.4 months, doubling the placebo group's 10.4 months (HR 0.67); median distant metastasis-free survival (mDMFS) was nearly 30 months (29.4 months vs 16.6 months placebo). Safety data showed 14% incidence of grade 3–4 treatment-related adverse events (TRAE); severe TRAEs occurred in 8%, with most immune-related events being grade 1 or 2. The adjuvant indication for residual EC or GEJC patients strongly supports its postoperative use.
(Abstract No.: 4001; Sun Young Rha)
The LEAP-015 trial aimed to evaluate the first-line efficacy of pembrolizumab (KEYTRUDA?) combined with lenvatinib (LENVIMA?) and chemotherapy in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal adenocarcinoma. Compared to standard chemotherapy, the combination showed statistically significant improvements in PFS and ORR, but the final analysis showed it failed to meet the primary endpoint of overall survival (OS) improvement. The safety and tolerability of the combination were consistent with prior studies, with no new safety signals observed. Merck and Eisai plan a full data assessment and will present complete results at the 2025 ASCO meeting — stay tuned.
(Abstract No.: LBA4002; Kohei Shitara)
DESTINY-Gastric04 is a global, randomized, open-label phase III trial enrolling 494 patients across Asia, Europe, and South America, evaluating trastuzumab deruxtecan (6.4 mg/kg) versus ramucirumab plus paclitaxel in second-line treatment of HER2-positive advanced gastric cancer. Interim analysis showed trastuzumab deruxtecan significantly improved overall survival (OS), making it the first HER2-targeted drug confirmed to provide survival benefits in phase III randomized trials for HER2-positive gastric cancer second-line treatment. The safety profile was consistent with previously known data.
(Abstract No.: 4003; Changsong Qi)
The results of this study will be presented at this conference. The prior phase I trial of CT041 showed remarkable results: 98 patients with CLDN18.2-positive advanced gastrointestinal tumors, including gastric and gastroesophageal junction adenocarcinoma, pancreatic cancer, cholangiocarcinoma, etc., were enrolled. The overall response rate (ORR) was 38.8%, disease control rate (DCR) was 91.8%, median progression-free survival (PFS) was 4.4 months (95% CI: 3.7–6.6), and median overall survival (OS) was 8.8 months (95% CI: 7.1–10.2). Additionally, 59 patients treated with monotherapy for gastric/gastroesophageal junction (GC/GEJ) cancer showed an ORR of 54.9%, DCR of 96.1%, median PFS of 5.8 months (95% CI: 4.1–8.0), and median OS of 9.0 months (95% CI: 7.0–11.9). Based on phase I data, the phase II results are highly anticipated.
In summary, the 2025 ASCO Annual Meeting has presented numerous cutting-edge studies and therapeutic advances in gastric cancer, undoubtedly bringing new hope and dawn to gastric cancer patients.
