Editor's note: Gastric cancer remains a leading cause of cancer-related mortality, particularly in patients with peritoneal metastases, for whom treatment options are limited. The DRAGON-01 trial, a multicenter, randomized phase 3 study presented by Dr. Chao Yan at the ASCO Gastrointestinal Cancers Symposium, aimed to evaluate the efficacy and safety of intraperitoneal (IP) plus intravenous (IV) paclitaxel combined with S-1 compared to the standard IV paclitaxel plus S-1 regimen.Noninvasive intraperitoneal chemotherapy (NIPS) has been explored as a promising treatment approach to enhance drug exposure in peritoneal metastasis while reducing systemic toxicity. Previous studies at our center have investigated multiple phase II and phase III trials, including DRAGON-01, to assess the effectiveness of NIPS. Historical trials from 2015 to 2024 have analyzed different combinations of paclitaxel and systemic therapies, with promising trends in survival outcomes.
The PHOENIX-GC trial, the first phase III randomized controlled trial evaluating NIPS in gastric cancer, showed a median survival time of 17.7 months for IP therapy versus 15.2 months for standard systemic therapy, with a hazard ratio of 0.72. While it did not meet statistical significance, it suggested initial clinical benefits of NIPS, supporting further investigation.
The DRAGON-01 trial enrolled a total of 238 patients across multiple centers, including Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and other leading institutions. Participants were randomized into two arms: an experimental arm receiving IP+IV paclitaxel plus S-1 and a control arm receiving IV paclitaxel plus S-1. Baseline characteristics between both groups were well-balanced, ensuring comparability in key prognostic factors such as age, sex, ECOG performance status, tumor burden, and previous treatments. Eligibility criteria included histologically confirmed gastric cancer, peritoneal metastasis confirmed by laparoscopy, and an ECOG-PS score of 0 or 1. Patients with distant metastasis outside the peritoneum or severe organ dysfunction were excluded.
CONSORT Diagram and Sample Size Rationale
A total of 246 patients were screened, with 238 patients meeting the inclusion criteria. The study was designed with a 2:1 randomization ratio, with 158 patients assigned to the NIPS group and 80 patients to the PS group. The hypothesis was that NIPS would improve median survival time (MST) from 11 to 22 months. Statistical power was set at 80%, with a significance level of 0.10 (one-sided) and an expected dropout rate of 10%.
Primary Endpoint: Overall Survival
The primary endpoint of the study was overall survival (OS). The results showed a significant improvement in the experimental arm. Median OS in the IP+IV paclitaxel plus S-1 group was 19.4 months (95% CI: 17.1-22.9), whereas in the IV paclitaxel plus S-1 group, it was 13.9 months (95% CI: 10.3-16.1). The hazard ratio (HR) was 0.66 (95% CI: 0.49-0.88, p = 0.0056), indicating a statistically significant survival benefit.
Secondary Endpoints: Conversion Surgery and Surgery Outcomes
A key secondary endpoint was the rate of conversion surgery, defined as achieving sufficient tumor shrinkage to allow surgical resection. Conversion surgery rates were higher in the experimental arm, with 50.7% of patients undergoing resection compared to 35.1% in the control group (p = 0.028). The R0 resection rate was 35.5% (95% CI: 30.5-45.6) in the experimental arm versus 20.9% (95% CI: 17.1-NA) in the control group. Postoperative complications were comparable between both groups, supporting the safety of conversion surgery after NIPS treatment.
Adverse Events and Safety Profile
The study also assessed treatment-related adverse events. Grade ≥3 adverse events were reported in 38.4% of patients in the experimental arm compared to 42.5% in the control arm (p = 0.562). The most commonly observed toxicities included neutropenia (40.4% in NIPS vs. 42.9% in PS), anemia, and thrombocytopenia. Port-related complications were noted in 12% of patients, with the most common being reflux/subcutaneous accumulation (12 cases grade 1-2, 6 cases grade 3), but these were generally manageable.
Conversion Surgery Indications
Conversion surgery was indicated in cases where peritoneal metastasis had disappeared, the primary tumor was deemed resectable, cytology was negative, and there was no evidence of distant metastasis. These criteria were crucial in determining patient eligibility for surgery following NIPS treatment.
Study Limitations
While the trial demonstrated significant benefits, certain limitations must be acknowledged. The study was conducted exclusively in an Asian population, which may limit the generalizability of findings to other ethnic groups and geographic regions. Additionally, the control regimens were based on guidelines prevalent at the time of study design, which may differ from current standard practices due to the rapid evolution of gastric cancer treatment strategies.
Conclusion and Clinical Implications
The DRAGON-01 trial provides strong evidence supporting the integration of IP+IV paclitaxel plus S-1 in treating gastric cancer patients with peritoneal metastasis. This regimen significantly prolongs survival and improves conversion surgery rates compared to IV-only treatment, with an acceptable safety profile. Conversion surgery criteria—including the disappearance of peritoneal metastasis, resectability of the primary tumor, negative cytology, and absence of distant metastases—were key determinants of surgical success. Further investigations and real-world data are warranted to confirm these findings and optimize patient selection criteria.
