Editor's note: From April 26 to April 27, 2024, the 2024 CSCO Guide will be held at Shangri-La Hotel, Jinan. The conference was co-sponsored by the Chinese Society of Clinical Oncology (CSCO) and the Beijing Heathosco Clinical Oncology Research Foundation. 【Yiyuehui】Sort out the updated points of the 2024 version of the gastric cancer guideline for you.
Comprehensive treatment of locally advanced gastric cancer
One
Catalog updates
Subheading adjustment: "Resectable gastric cancer" was adjusted to "Resectable esophagogastric junction/gastric adenocarcinoma".
"Unresectable locally advanced gastric cancer" was adjusted to "unresectable locally advanced esophagogastric junction/gastric adenocarcinoma".
Two
Text modification for the treatment of gastric cancer that can be surgically removed
Treatment for stomach cancer that can be surgically removed
Surgical resectable gastric cancer should be treated according to clinical stage. For early-stage gastric cancer that meets the indications, endoscopic treatment, i.e., endoscopic mucosal resection (EMR) and endoscopic submucosal resection (ESD), are the preferred treatments.
For patients who are not candidates for endoscopic therapy, open or laparoscopic surgery may be used. For non-esophagogastric junction advanced gastric cancer, the current standard of care is D2 surgical resection combined with postoperative adjuvant chemotherapy, and for patients with late stage (clinical stage III or above), perioperative chemotherapy mode can be selected. For advanced esophagogastric junction cancer, neoadjuvant chemoradiotherapy or preoperative chemotherapy may be an option. There is currently a lack of evidence-based evidence for disease progression after neoadjuvant therapy and the optimal regimen for salvage therapy in patients with R0 resection who cannot achieve it.
For patients who do not have distant metastases and have not received preoperative radiotherapy, radiotherapy is an alternative treatment, and it is recommended that multidisciplinary discussions be conducted on an individual basis for such patients and the optimal treatment regimen should be formulated based on molecular markers (e.g., MMR, HER-2, PD-L1). In addition, chemoradiotherapy may be used as a treatment option for resectable patients who are not candidates for surgical treatment due to individual factors, but the best treatment strategy must be selected after full consideration of individual specificities, including molecular typing (see Comprehensive Treatments for Unresectable Gastric Cancer).
Three
Modification of the recommended level of the overall treatment strategy
Holistic treatment strategy
II 期（cT1-2N1-3M0/ cT3-4N0M0）：食管胃结合部肿瘤，适宜手术的 II 级推荐胃切除术 D2（1A类）+ 辅助化疗调整为胃切除术 D2 + 辅助化疗（1B 类）。
III 期（cT3-4aN1-3M0）：食管胃结合部肿瘤，适宜手术的 II 级推荐胃切除术 D2（1A类）+ 辅助化疗调整为胃切除术 D2+ 辅助化疗（1B 类）。
Four
Postoperative adjuvant chemotherapy, commonly used regimens
Increase the number of specific drug cycles, DS-S1 supplementation regimen.
Medication cycle: 8 cycles for XELOX, SOX, XP and 12 cycles for FOLFOX.
DS-S1 supplemental regimen: 1 cycle of S-1 monotherapy, 7 cycles of DS, post-S-1 monotherapy to 1 year.
Tigio monotherapy: repeated every 21 days for 1 year.
Five
Update of annotations for postoperative adjuvant therapy for resectable gastric cancer
In 2023, ESMO announced the results of the 5-year follow-up of the RESOLVE study, and for patients with cT4a/N+M0 or cT4b/NxM0 locally advanced gastric/esophagogastric junction adenocarcinoma, the 8-cycle sox adjuvant chemotherapy regimen after D2 radical resection was non-inferior to the XELOX regimen at 5 years 0S and DFS.
The results of the ATTRACTION-5 study published by ASCO in 2023 showed that there was no difference in whether adjuvant chemotherapy was combined with nivolumab in patients undergoing D2 or above surgery in stage III, and the median RFS and 0S were not reached in both groups, and the efficacy of immunotherapy in gastric adjuvant therapy still needs to be explored more.
Six
Update on perioperative immunotherapy annotations for dMMR-type gastric cancer
FOR PATIENTS WITH DMMR, PERIOPERATIVE IMMUNOTHERAPY IS THE FUTURE DEVELOPMENT TREND, AND THE GERCOR NEONIPIGA STUDY AND THE INFNITY STUDY BOTH SHOWED THAT THE PCR RATES OF PREOPERATIVE NEOADJUVANT THERAPY WITH PD1/PD-L1 ANTIBODY COMBINED WITH CTLA-4 ANTIBODY WERE 59% AND 60%, RESPECTIVELY. In the gastric cancer cohort of the IMHOTEP study (16 patients with resectable dMMR/MSI tumors (or EBV+ gastric cancer) who were candidates for radical surgery, pembrolizumab had a pCR of 25% for perioperative treatment. The DANTE study demonstrated that FLOT + atezolizumab improved tumor downstage compared with FLOT, with pCR rates of 24% and 15%, respectively, and pCR rates of 63% in patients with MSI-H. For neoadjuvant treatment of dMMR gastric cancer, a regimen containing immune checkpoint inhibitors or participation in a clinical trial can be used.
Seven
Perioperative immunotherapy for gastric cancer with pMMR annotations updated
In 2023, three phase III RCTs of perioperative immunotherapy combined with chemotherapy for pMMR gastric cancer published recent efficacy and safety data. The results of the MATTERHORN study, the KEYNOTE-585 study, and the DRAGON IV/CAP 05 study all showed consistent improvement in pCR in perioperative immunotherapy combined with chemotherapy for pMMR gastric cancer, but there is a lack of long-term survival data and cannot be used as a routine clinical recommendation. Therefore, the above patients are preferentially recommended to participate in clinical studies.
Targeted therapy for metastatic gastric cancer
One
Targeting CLDN18.2
The status of GLOW research data and multi-technology drug targeting CLDN18.2 is added in the form of annotations, evidence source: Based on the results of the SPOTLIGHT and GLOW (Chinese registration study) studies published and published in full in 2023.
Molecular testing update: The level of recommendation in the form has been changed from Level I recommendation in 2023 to Level II recommendation in 2024.
Annotation added: Claudin 18.2 was tested by immunohistochemistry, and the current positive interpretation criteria are only from clinical trials.
Claudin 18.2 positivity is determined by the intact tumor cells, the intensity of basolateral or lateral membrane staining, and the percentage of tumor cell membrane staining. However, different clinical studies use different interpretation criteria.
Two
靶向Her-2
New Level III recommendation for third-line and above-line therapy: trastuzumab (DS-8201) (Class 2A);
Annotation added: Added DESTINY-Gastric06 study data results.
Three
靶向VEGFR
Annotated addition of fruquintinib in combination with paclitaxel in second-line treatment of advanced gastric cancer, rationale and source of evidence: Based on the results of the FRUTIGA Phase III clinical study.
Added note: Anti-angiogenic drugs approved for advanced gastric cancer include ramucirumab (anti-VEGFR2 monoclonal antibody) and apatinib mesylate (VEGFR-2 small molecule tyrosine kinase inhibitor). In the Phase III study of FRUTIGA, in which fruquintinib plus paclitaxel compared with placebo plus paclitaxel, had advanced esophagogastric junction or gastric adenocarcinoma that had progressed after first-line chemotherapy with fluoropyrimidine or platinum-based chemotherapy, PFS and OS were the twin primary endpoints of the study, fruquintinib plus paclitaxel significantly improved mPFS (5.55 months vs. 2.73 months, P<0.0001) and improved ORR (42.5% vs. 22.4%, P<0.0001), there was a prolongation trend in mOS (9.6 months vs. 8.4 months, P=0.6064), and no new safety signals were found.
Immunotherapy for metastatic gastric cancer
One
First-line immunotherapy for HER2-positive gastric cancer
Level I Recommendation:
PD-L1 CPS≥1，帕博利珠单抗+曲妥珠单抗+XELOX/PF（1A类，1B类）；
PD-L1 CPS<1，曲妥珠单抗联合奥沙利铂/顺铂+5-FU/卡培他滨（1A类）。
Two
First-line immunotherapy for HER2-negative gastric cancer
Level I Recommendation:
新增推荐 ：PD-L1 CPS≥5，CAPOX联合舒格利单抗（1A 类）（GEMSTONE-303 研究）；
PD-L1 CPS≥10， CAPOX/FP联合帕博利珠单抗（1A 类）（KEYNOTE-859 研究）。
Level II Recommendation:
新增推荐：PD-L1 CPS < 10 或检测不可及 CAPOX 或 FP 联合帕博利珠单抗（1B类）。
Update Format:
Adjust the position of the table and add footnotes.
* Fluorouracil includes 5-FU, capecitabine, and tigio; Taxanes include paclitaxel, docetaxane, and nab-paclitaxel.
* When immune checkpoint inhibitors are contraindicated.
* When chemotherapy is contraindicated or chemotherapy is not suitable.
Three
MMR/MSI H 人群
First-line therapy: dMMR/MSI-H, regardless of HER2 status, nivolumab plus ipilimumab (class 2B) was adjusted from a level III recommendation to a level II recommendation.
New addition to second-line therapy: dMMR/MSI-H regardless of HER2 status, grade I recommendation for serplulimab (category 2A evidence).
Four
First-line immunotherapy for rare subtypes of gastric cancer
As a special type of gastric cancer, first-line treatment of AFPGC is considered SOX + apatinib + camrelizumab (phase II study) (category 2B evidence/level II recommendation).
As a rare type, a table is added.
Five
Additional note: Helicobacter pylori infection is associated with efficacy of immunotherapy for gastrointestinal tumors
It was confirmed that Helicobacter pylori infection is a favorable factor for immunotherapy of gastric cancer by shaping the "hot" tumor microenvironment of gastric cancer.
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