Lancet Oncology (IF=41) Significant progress!

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iNature globally, gastric cancer is the fifth most common malignant tumor and the third most deadly cancer
.

The majority of gastric cancer patients are from East Asia, and 47% of patients are from China
.

Patients in high-risk areas are often diagnosed as late and have a poor prognosis
.

 Improving the prognosis of these patients is necessary but challenging
.

The optimal perioperative chemotherapy regimen for locally advanced gastric cancer has not yet been determined
.

This and the evaluation of perioperative and postoperative S-1 and oxaliplatin (SOX) and postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy And safety
.

On July 9, 2021, the Peking University Ji Jiafu team published an online publication titled "Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal" in Lancet Oncology (IF=41.
32) on July 9, 2021.
junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial" research paper.
This open-label, phase 3, superiority and non-inferiority controlled trial was conducted in 27 hospitals in China.
Randomized trial of inferiority
.

The study recruited patients 18 years of age or older who had not received anti-tumor therapy, and these patients had historically proven cT4a N+ M0 or cT4b Nany M0 gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance score of 70 or higher
.

Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) to receive assisted CapOx, assisted SOX, or perioperative SOX through an interactive web response system (layered by participating centers and Lauren classification)
.

The primary endpoint is the 3-year disease-free survival assessed in the modified intention-to-treat population
.

Between August 15, 2012 and February 28, 2017, 1094 patients were screened, 1022 (93%) patients were included in the modified intention-to-treat population, of which 345 (34%) patients were assigned to the adjuvant CapOx There were 340 (33%) patients in the auxiliary SOX group and 337 (33%) patients in the perioperative SOX group
.

The 3-year disease-free survival rate of the CapOx adjuvant group was 51.
1% (95% CI 45·5–56·3), and the SOX adjuvant therapy group was 56·5% (51.
0-61·7), and the perioperative period The SOX group was 59.
4% (53·8–64·6)
.

Compared with the adjuvant CapOx group, the hazard ratio (HR) of the perioperative SOX group was 0.
77 (95% CI 0·61–0·97; Wald p=0·028), and the hazard ratio (HR) of the SOX adjuvant treatment group ( HR) is 0·86 (0·68 –1·07; Wald p=0·17)
.

The most common grade 3-4 adverse events were neutropenia (32 [12%] of 258 patients in the adjuvant CapOx group, 21 [8%] of 249 patients in the adjuvant SOX group, and 310 perioperative period- Patients in the SOX group)
.

Seven out of 258 patients (3%) in the CapOx adjuvant therapy group reported serious adverse events, of which 2 were related to treatment; 8 out of 249 patients in the SOX adjuvant therapy group (3%), of which 2 were related to treatment ; Perioperative-SOX group has 7 cases (2%) of 310 patients, 4 of which are related to treatment
.

No deaths related to treatment were reported
.

In conclusion, in patients with locally advanced gastric cancer undergoing D2 gastrectomy, perioperative SOX has a clinically significant improvement compared with adjuvant CapOx; in these patients, adjuvant SOX is not inferior to adjuvant CapOx
.

Perioperative SOX can be regarded as a new treatment option for patients with locally advanced gastric cancer
.

Globally, gastric cancer is the fifth most common malignant tumor and the third most deadly cancer
.

The majority of gastric cancer patients are from East Asia, and 47% of patients are from China
.

The incidence is also high in South America and some European countries
.

Patients in high-risk areas are often diagnosed as late and have a poor prognosis
.

 Improving the prognosis of these patients is necessary but challenging
.

The standard treatment for locally advanced gastric cancer is D2 gastrectomy, combined with perioperative chemotherapy
.

Capecitabine (Capecitabine) combined with oxaliplatin (CapOx) is recommended for postoperative treatment
.

Perioperative use of epirubicin (epirubicin), cisplatin and fluorouracil or the National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology guidelines also recommend the use of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) It is used for patients with cT2-4 or N+ and M0 tumors; however, this method has not been approved worldwide
.

The optimal sequence and combination of perioperative treatment are still controversial (for example, whether surgery should be followed by postoperative adjuvant chemotherapy or neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy)
.

In addition, the clinical benefit of neoadjuvant chemotherapy for patients with significant local tumor invasion or lymph node metastasis (ie cT4a N+ M0 or cT4b Nany M0 disease) has not been determined
.

Fluoropyrimidine-based chemotherapy is still the mainstay of gastric cancer treatment, including two oral derivatives: S-1 and capecitabine
.

S-1, which is widely used in the treatment of gastric cancer in Asia, is associated with fewer adverse events in contrast to fluorouracil, and is increasingly used in Europe and North America
.

Many trials have observed different perioperative regimens, including oxaliplatin (SOX)-assisted S-1 and cisplatin neo-assisted S-1
.

Patients who received the S-1 regimen tolerated the drug well, and the regimen showed good efficacy in perioperative and metastatic trials.
In the CLASSIC trial, 99% of patients who received adjuvant CapOx had adverse events
.

Therefore, the potential benefits of SOX in neoadjuvant or adjuvant chemotherapy—fewer adverse events and better efficacy—are worth exploring in a phase 3 study
.

Large-scale randomized trials have not been conducted to compare perioperative SOX with standard postoperative CapOx.
The efficacy and safety of SOX adjuvant chemotherapy need to be investigated in prospective trials
.

The purpose of this study is to evaluate the efficacy of perioperative SOX and auxiliary CapOx, and determine whether auxiliary SOX is not inferior to auxiliary CapOx in terms of mortality and perioperative complications
.

The main hypothesis is that perioperative period-SOX can improve disease-free survival compared with adjuvant-CapOx, and adjuvant-SOX is not inferior to adjuvant-CapOx
.

 The study conducted this open-label, phase 3, superiority and non-inferiority randomized trial in 27 hospitals in China
.

The study recruited patients 18 years of age or older who had not received anti-tumor therapy, and these patients had historically proven cT4a N+ M0 or cT4b Nany M0 gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance score of 70 or higher
.

Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) through the interactive network response system to receive supplementary CapOx (8 cycles after surgery, oxaliplatin 130 mg intravenously on the first day of each 21-day cycle /m2, plus oral capecitabine 1000 mg/m2 twice a day, supplementary SOX (8 cycles after surgery, intravenous injection of oxaliplatin 130 mg/m2 on the first day of each 21-day cycle, plus Oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on the first day of every 21 days plus oral S-1 40-60 mg twice a day, Three cycles before surgery and five cycles after surgery; then three cycles of S-1 monotherapy)
.

The primary endpoint is the 3-year disease-free survival assessed in the modified intention-to-treat population
.

Perform a safety analysis in patients receiving at least one dose of the designated treatment
.

This study is registered with ClinicalTrials.
gov, NCT01534546
.

Between August 15, 2012 and February 28, 2017, 1094 patients were screened, 1022 (93%) patients were included in the modified intention-to-treat population, of which 345 (34%) patients were assigned to the adjuvant CapOx There were 340 (33%) patients in the auxiliary SOX group and 337 (33%) patients in the perioperative SOX group
.

 The 3-year disease-free survival rate of the CapOx adjuvant group was 51.
1% (95% CI 45·5–56·3), and the SOX adjuvant therapy group was 56·5% (51.
0-61·7), and the perioperative period The SOX group was 59.
4% (53·8–64·6)
.

Compared with the adjuvant CapOx group, the hazard ratio (HR) of the perioperative SOX group was 0.
77 (95% CI 0·61–0·97; Wald p=0·028), and the hazard ratio (HR) of the SOX adjuvant treatment group ( HR) is 0·86 (0·68 –1·07; Wald p=0·17) 
.

The most common grade 3-4 adverse events were neutropenia (32 [12%] of 258 patients in the adjuvant CapOx group, 21 [8%] of 249 patients in the adjuvant SOX group, and 310 perioperative period- Patients in the SOX group)
.

Seven out of 258 patients (3%) in the CapOx adjuvant therapy group reported serious adverse events, of which 2 were related to treatment; 8 out of 249 patients in the SOX adjuvant therapy group (3%), of which 2 were related to treatment ; Perioperative-SOX group has 7 cases (2%) of 310 patients, 4 of which are related to treatment
.

No deaths related to treatment were reported
.

In conclusion, in patients with locally advanced gastric cancer undergoing D2 gastrectomy, perioperative SOX has a clinically significant improvement compared with adjuvant CapOx; in these patients, adjuvant SOX is not inferior to adjuvant CapOx
.

Perioperative SOX can be regarded as a new treatment option for patients with locally advanced gastric cancer
.

Statement: This study is a clinical trial and does not constitute medication guidance.
Please follow the doctor's instructions for specific medication
.

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