"The Lancet-Oncology": Revolutionize the perioperative treatment of locally advanced gastric cancer

The latest global cancer burden data from the International Agency for Research on Cancer (IARC) in 2020 shows that gastric cancer is the fourth leading cause of cancer-related deaths in the world and the third leading cause of cancer deaths in China

In the past weekend, "The Lancet-Oncology" published the results of a decade of RESOLVE research.

The paper pointed out that this is "the first large-scale randomized study that directly compares neoadjuvant therapy and adjuvant therapy in locally advanced gastric cancer patients", and it is also "the first to show that perioperative SOX chemotherapy is significantly improved compared to CapOx adjuvant therapy.

Professor Lin Lin and Professor Ji Jiafu from Peking University Cancer Hospital are the corresponding authors.

Currently, the standard treatment for locally advanced gastric cancer is D2 gastrectomy combined with perioperative chemotherapy

Currently, fluoropyrimidine-based chemotherapy is still the mainstay of gastric cancer treatment, which includes two oral drugs: S-1 and capecitabine

Therefore, the research team considered exploring the potential benefits of SOX (S-1 combined with oxaliplatin) in the perioperative period (neoadjuvant or adjuvant chemotherapy), and combined with standard postoperative CapOx (capecitabine combined with oxaliplatin) The plans were compared, and the RESOLVE study came into being

It is worth noting that this study adopted a dual-endpoint design: it also verified the overall superiority of perioperative SOX chemotherapy versus CapOx adjuvant chemotherapy, and the non-inferiority of SOX versus CapOx for adjuvant therapy; passed 3 Years of disease-free survival are assessed

This open-label, phase 3 randomized trial was carried out in 27 hospitals in China, and recruited locally advanced stage (cT4a N+ M0 or cT4b Nany M0) confirmed by histology from August 15, 2012 to February 28, 2017.

Radical gastrectomy was performed by 45 experienced surgeons.

Data analysis as of May 9, 2020 shows that among the mITT population, the 3-year disease-free survival rate of the adjuvant CapOx regimen chemotherapy group was 51.

Compared with the adjuvant CapOx chemotherapy group, the risk of disease recurrence or death in the perioperative SOX chemotherapy group was significantly reduced by 23% (HR 0.

▲Compared with adjuvant CapOx chemotherapy (blue line), perioperative SOX chemotherapy (red line, Figure A) has a higher 3-year disease-free survival rate; adjuvant SOX chemotherapy (green line, Figure B) has a higher 3-year disease-free survival rate.

The R0 resection rate of the perioperative SOX regimen chemotherapy group was higher than that of the adjuvant CapOx regimen chemotherapy group (93% vs 87%)

As of data analysis, the secondary endpoint of overall survival has not been reached, and data is still being accumulated

The most common grade 3-4 adverse event was neutropenia (12% in the adjuvant CapOx chemotherapy group, 8% in the adjuvant SOX chemotherapy group, and 10% in the perioperative SOX chemotherapy group)

Based on these data, the research team believes that perioperative SOX chemotherapy is effective and safe, and can be used as a new treatment option for patients with resectable locally advanced T4 gastric cancer
.

The conclusions of this study have also changed clinical practice.
At present, CSCO gastric cancer diagnosis and treatment guidelines have newly recommended perioperative SOX chemotherapy.
It is recommended that patients with cT4a N+ or cT4b Nany gastric cancer receive neoadjuvant SOX treatment before surgery, or add neoadjuvant therapy Clinical trials
.

Reference

[1] Xiaotian Zhang, et al.
, (2021).
Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open- label, superiority and non-inferiority, phase 3 randomised controlled trial.
The Lancet Oncology, DOI: https://doi.
org/10.
1016/S1470-2045(21)00297-7