CRITICS-II Trial Identifies Optimal Preoperative Strategy for Resectable Gastric Cancer
核心洞察
The CRITICS-II phase II trial evaluated three preoperative-only treatment strategies in 201 patients with resectable gastric cancer (搜索) across 16 Dutch centers.
Chemotherapy followed by chemoradiotherapy achieved the highest 1-year event-free survival at 84%, compared to 68% for chemotherapy alone and 78% for chemoradiotherapy alone.
The study demonstrates that preoperative chemotherapy alone was insufficient, while total neoadjuvant therapy emerges as the preferred strategy for further development.
The CRITICS-II trial, a multicenter randomized phase II study presented at the ASCO Gastrointestinal Cancers Symposium, has identified total neoadjuvant therapy as the optimal preoperative strategy for patients with resectable gastric cancer (搜索). The study compared three preoperative-only treatment approaches, with chemotherapy followed by chemoradiotherapy demonstrating superior efficacy outcomes.
Study Design and Patient Population
Conducted across 16 centers in the Netherlands between 2017 and 2024, the trial enrolled 201 patients with clinical stage IB–IIIC resectable gastric or gastroesophageal junction adenocarcinoma (搜索). Eligible patients had no distant metastases, negative staging laparoscopy, WHO performance status 0–1, and were aged ≥18 years.
Patients were randomized to three preoperative-only treatment arms:
- Arm 1: Four cycles of docetaxel, oxaliplatin, and capecitabine (DOC)
- Arm 2: Two cycles of DOC followed by chemoradiotherapy (45 Gy in 25 fractions with concurrent weekly paclitaxel and carboplatin)
- Arm 3: Chemoradiotherapy alone (45 Gy in 25 fractions with concurrent paclitaxel and carboplatin)
All patients proceeded to surgery consisting of total or subtotal gastrectomy with extended lymphadenectomy, requiring removal of at least 15 lymph nodes.
Primary Efficacy Results
The primary endpoint of 1-year event-free survival (EFS) clearly distinguished between treatment strategies. Using a pick-the-winner design where ≥60% was considered insufficiently active and ≥75% sufficiently active, the results showed:
- Chemotherapy alone: 68% 1-year EFS (95% CI, 58%-80%), failing to meet the efficacy threshold
- Chemotherapy plus chemoradiotherapy: 84% 1-year EFS (95% CI, 75%-84%), meeting criteria for sufficient activity
- Chemoradiotherapy alone: 78% 1-year EFS (95% CI, 69%-88%), meeting criteria for sufficient activity
Overall survival at 1 year followed a similar pattern, with rates of 74% for chemotherapy alone, 89% for chemotherapy plus chemoradiotherapy, and 84% for chemoradiotherapy alone.
Safety and Surgical Outcomes
Preoperative toxicity was acceptable across all arms, with grade 3–4 adverse events occurring in 52% of patients receiving chemotherapy alone, 53% in the combination arm, and 43% in the chemoradiotherapy-only arm. The chemoradiotherapy-alone arm demonstrated the lowest severe toxicity burden.
Surgical resection was performed in most patients across all treatment arms, with curative-intent surgery undertaken in 60, 58, and 63 patients in arms 1, 2, and 3, respectively. Pathologic complete response rates were 8%, 20%, and 13% in the respective treatment arms.
Clinical Implications and Multidisciplinary Approach
According to Marcel Verheij, MD, PhD, from the Department of Radiation Oncology at Radboud University Medical Center, the collaboration between radiation oncologists and surgeons is crucial for optimizing outcomes. "What is important in the interplay between surgeons and radiation oncologists is that surgeons know where we deposit our radiation dose because that may affect the technique and the complications of surgical intervention," Verheij noted.
The study addresses a significant clinical challenge in gastric cancer (搜索) treatment, where compliance with postoperative therapy is consistently low, particularly after major gastric surgery. Preoperative treatment offers potential advantages including improved treatment adherence, tumor downstaging, and increased rates of complete (R0) resection.
Future Directions
The CRITICS-II trial results demonstrate that while both chemotherapy followed by chemoradiotherapy and chemoradiotherapy alone were sufficiently effective, the combination approach consistently showed the most favorable balance. This strategy achieved the highest event-free and overall survival, the highest pathological complete response rate, and the lowest rate of surgery-related complications.
The findings identify total neoadjuvant therapy consisting of chemotherapy followed by chemoradiotherapy as the preferred preoperative strategy for patients with resectable gastric cancer (搜索) when adjuvant treatment is omitted. This approach appears feasible, effective, and safe, emerging as the leading candidate for further evaluation in phase III development, particularly in the context of organ-sparing treatment strategies.