A new phase II randomized clinical trial has found that perioperative chemotherapy with docetaxel, oxaliplatin and S-1 (DOS) significantly improved major pathological response rates compared to oxaliplatin and S-1 (SOX) in patients with locally advanced gastric or gastroesophageal junction adenocarcinoma. The study, called MATCH, was conducted at the National Cancer Center in China and published on March 8, 2024 in Gastric Cancer.
The trial aimed to evaluate whether adding docetaxel to the combination of oxaliplatin and S-1 could provide additional clinical benefits compared to the doublet regimen in the perioperative treatment setting for locally advanced gastric cancer in Asian patients. While triplet chemotherapy regimens like FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) have become standard in Europe, doublet regimens are more commonly used in Asia. This study helps address whether triplet regimens may also be advantageous for Asian populations.
The open-label study enrolled 154 patients between August 2015 and December 2019. Patients were randomized 1:1 to receive either 4 cycles of preoperative DOS or SOX chemotherapy, followed by D2 gastrectomy and an additional 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR), defined as less than 10% residual tumor in the surgical specimen.
Key inclusion criteria were: - Age ≥18 years - Histologically confirmed gastric or gastroesophageal junction (Siewert II/III) adenocarcinoma - HER2-negative - Clinical stage T3-4 NanyM0 - No prior treatment - ECOG performance status ≤1 - Adequate organ function
Patients with other malignancies in the past 5 years, allergies to the study drugs, or distant metastases were excluded.
The median age of participants was 60 years (range 26-73) and 78.9% were male. Most patients had advanced disease, with 37.4% classified as stage IIIC. This represents a more advanced population compared to some previous perioperative chemotherapy trials.
The key results showed: - Significantly higher MPR rate with DOS vs SOX (25.4% vs 11.8%, p=0.04) - Higher R0 resection rate with DOS (78.9% vs 61.8%, p=0.02) - Trend toward improved 3-year progression-free survival with DOS (52.3% vs 35.0%, HR 0.667, p=0.07) - Trend toward improved 3-year overall survival with DOS (57.5% vs 49.2%, HR 0.685, p=0.11) - Patients achieving MPR had significantly better survival outcomes - Similar rates of treatment completion and adverse events between groups - Lower rates of thrombocytopenia with DOS
The DOS regimen demonstrated higher antitumor activity, with a 13.6% absolute improvement in MPR rate. It also showed a promising trend in translating this improved tumor response into long-term survival benefits, with a 33.3% reduction in the risk of disease progression or death. Interestingly, the triplet regimen did not increase toxicity compared to the doublet, likely due to the reduced oxaliplatin dose used.
The study had several limitations to consider. As a single-center phase II trial, the results need to be confirmed in a larger, multicenter phase III study. The survival advantage with DOS did not reach statistical significance, possibly due to the relatively small sample size. Additionally, diagnostic laparoscopy was not mandatory at baseline, which may have led to the inclusion of some patients with peritoneal metastases. A relatively high proportion of patients (26.5%) did not proceed to surgery, which could impact the interpretation of outcomes.
The authors concluded that perioperative DOS chemotherapy significantly improved major pathological response rates and showed a trend toward improved progression-free survival compared to SOX in locally advanced gastric cancer. They suggest it may be considered a preferred option for perioperative treatment in Asian patients and merits further investigation in phase III trials.
This study has several potential clinical implications if the results are confirmed in larger trials: 1. It provides evidence that triplet chemotherapy regimens may offer benefits over doublets in Asian gastric cancer populations, similar to findings in Western patients. 2. The favorable toxicity profile of DOS, particularly the lower rates of thrombocytopenia, may make it an attractive option compared to other triplet regimens like FLOT. 3. The improved R0 resection rates with DOS could lead to better long-term outcomes for patients. 4. The strong correlation between achieving MPR and improved survival supports the use of MPR as a surrogate endpoint in future neoadjuvant gastric cancer trials. 5. The DOS regimen may be a good combination partner for emerging immunotherapy and targeted therapy approaches in the perioperative setting.
While these results are promising, it is important to note that the study was relatively small and the survival benefits did not reach statistical significance. Additionally, the patient population had more advanced disease than some previous perioperative chemotherapy trials, which may impact the generalizability of results. Larger phase III trials are needed to definitively establish the role of DOS chemotherapy in the perioperative treatment of gastric cancer.
Overall, this study provides valuable data on optimizing chemotherapy regimens for Asian patients with locally advanced gastric cancer. It suggests that adding docetaxel to oxaliplatin and S-1 may improve outcomes without substantially increasing toxicity. As gastric cancer remains a significant health burden in Asia, refining perioperative treatment strategies has the potential to meaningfully impact patient care. Oncologists treating gastric cancer patients should follow future research on the DOS regimen with interest.
The study was conducted by researchers at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Funding sources were not specified in the published paper. As perioperative treatment for gastric cancer continues to evolve, with the integration of targeted therapies and immunotherapies, studies like MATCH provide important data to help guide treatment selection and inform the design of future trials.
References
Jiang Z, Xie Y, Zhang W, et al. Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial. Gastric Cancer. 2024;27(3):571-579. doi:10.1007/s10120-024-01471-z
