Phase II Trial Shows Promise for Toripalimab-FLOT Combination in Gastric Cancer with Peritoneal Metastasis
Key Insights
A phase II trial demonstrated that toripalimab combined with FLOT (search) chemotherapy achieved a 25% R0 resection conversion rate in gastric cancer (search) patients with peritoneal metastasis (search), a condition with historically poor prognosis.
The combination therapy resulted in a median overall survival of 10.8 months and progression-free survival of 6.5 months, with an objective response rate of 35% and disease control rate of 80%.
Grade 3-4 treatment-related adverse events occurred in 35% of patients, primarily neutropenia (search), while patients who underwent conversion surgery showed trends toward improved survival outcomes.
A single-arm phase II clinical trial has demonstrated promising results for combining toripalimab, an anti-PD-1 (search) monoclonal antibody, with FLOT (search) chemotherapy as conversion therapy for gastric cancer (search) patients with peritoneal metastasis (search). The study, conducted at The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (search), achieved a 25% R0 resection conversion rate in this challenging patient population.
Study Design and Patient Population
The trial enrolled 20 patients aged 18-80 years with histologically and laparoscopically confirmed gastric adenocarcinoma (search) with peritoneal metastasis (search) between April 2021 and April 2023. All patients had an Eastern Cooperative Oncology Group Performance Status of 0 or 1 and were eligible for surgery. The median follow-up duration was 10.8 months.
Patients received toripalimab 3 mg/kg intravenously plus FLOT (search) chemotherapy (docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m², and 5-FU 2600 mg/m²) administered every 14 days for up to four cycles. After treatment, surgical feasibility was determined by a multidisciplinary team meeting.
Clinical Outcomes
The primary endpoint of R0 resection conversion rate was achieved in 5 of 20 patients (25%). Among these patients, 40% achieved tumor regression grade 1 (TRG1) and 60% achieved TRG2. The objective response rate was 35%, with 7 patients achieving partial response, while the disease control rate reached 80%.
Survival outcomes showed a median overall survival of 10.8 months (95% CI, 7.5-NR) with a 1-year survival rate of 48.1%. The median progression-free survival was 6.5 months (95% CI, 3.6-12.5) with a 1-year PFS rate of 22.5%.
Patients who underwent conversion surgery demonstrated superior survival outcomes compared to those who did not. The conversion group achieved an estimated median overall survival of 25.4 months versus 9.0 months in the non-conversion group, though the limited sample size precluded definitive statistical conclusions.
Safety Profile
The combination therapy showed manageable toxicity, with 95% of patients experiencing adverse events of any grade. Grade 3-4 treatment-related adverse events occurred in 35% of participants, with neutropenia (search) being the most common severe toxicity affecting 5 patients. These adverse events led to treatment discontinuation in 5 patients before surgery.
Of the 20 enrolled patients, 13 (65%) completed the planned four cycles of conversion therapy, while treatment was discontinued in half of the cohort following conversion therapy due to various reasons including toxicity and disease progression.
Surgical Outcomes
All five patients who underwent surgery received total gastrectomy with D2 lymph node dissection, with one patient also receiving para-aortic lymph node dissection. No peritoneal metastasis (search) was found during surgery in these patients, and all achieved negative cytology conversion. Importantly, no Clavien-Dindo grade IIIa or higher postoperative complications were observed.
Clinical Significance
This study represents the first prospective trial evaluating the conversion efficacy of FLOT (search) chemotherapy combined with PD-1 (search) inhibition in gastric cancer (search) patients with peritoneal metastasis (search). The results compare favorably to historical data showing approximately 5% conversion rates with systemic chemotherapy alone in this patient population.
The median overall survival of 10.8 months exceeded typical outcomes for gastric cancer (search) patients with peritoneal metastasis (search) receiving systemic chemotherapy, which typically range from 5.6 to 8.4 months. These findings suggest that adding toripalimab to chemotherapy might represent a viable treatment option for this challenging patient population.
Study Limitations
The researchers acknowledged several limitations, including the single-arm design requiring comparisons with historical controls, limited patient numbers from a single center, and potential selection bias from the surgical approach. The study's exploratory phase II design achieved 69% power to detect the hypothesized effect size, below the conventional 80% threshold but deemed acceptable given the challenges in recruiting this specific patient population.