Gastric Cancer Landmark Atlas

What did the researchers want to learn?

In operable gastric, esophagogastric junction or lower esophageal cancers, is giving chemotherapy before and after surgery better than surgery alone?

What did this study change?

It became one of the key studies showing the importance of chemotherapy spread across the period before and after surgery.

Benefit for patients

Relevant to patients with operable gastric cancer.

What did the research find?

The five-year survival rate was about 36% in the chemotherapy group and 23% in the surgery-alone group (hazard ratio for death 0.75; p=0.009).

Who does this apply to?

The ECF chemotherapy used is an older regimen that FLOT has replaced in many patients today. The study covers not only gastric cancer but also tumors of the junction region and the lower esophagus.

What did the researchers want to learn?

In resectable gastric or esophagogastric junction cancer, is FLOT chemotherapy before and after surgery better than the older ECF/ECX regimen?

What did this study change?

In suitable resectable gastric / GEJ cancer, perioperative FLOT became the reference chemotherapy in many centers.

Benefit for patients

Relevant to patients with operable gastric/GEJ adenocarcinoma.

What did the research find?

Median overall survival was reported as 50 months in the FLOT group and 35 months in the ECF/ECX group (hazard ratio [HR] 0.77). This does not mean every patient will live 50 months; FLOT4 did not compare FLOT with CROSS.

Who does this apply to?

For patients who are operable and in good performance status. It is not the same as metastatic disease or East Asian adjuvant approaches. Side-effect management and nutritional support are critical. The comparison with CROSS is in ESOPEC.

What did the researchers want to learn?

In operable gastric / gastroesophageal junction (GEJ) cancer, does adding durvalumab to FLOT improve outcomes?

What did this study change?

In suitable resectable patients, perioperative FLOT plus durvalumab was strengthened as an option.

Benefit for patients

Potential for longer event-free time and overall survival.

What did the research find?

Lancet 2026 final overall survival (OS): hazard ratio (HR) for death 0.78 (95% confidence interval [CI] 0.63–0.96). An event-free survival (EFS) benefit had also been reported earlier (2-year EFS 67.4% vs 58.5%). It does not mean automatic immunotherapy for all gastric cancer patients; licensing is separate by country (US FDA November 2025).

Who does this apply to?

Resectable gastric / GEJ adenocarcinoma. Not to be confused with metastatic CheckMate 649 or with thoracic squamous cell carcinoma. Immune-related toxicity; access in Turkey / EMA (European Medicines Agency) is not automatically equal to FDA approval.

What did the researchers want to learn?

Does adding radiotherapy before surgery to perioperative chemotherapy prolong survival?

What did this study change?

It did not support routinely adding preoperative radiotherapy to every operable gastric cancer.

Benefit for patients

Relevant to patients with operable gastric/GEJ cancer.

What did the research find?

The study's main goal, a prolongation of survival, could not be shown (median survival 46 months and 49 months; hazard ratio 1.05). Improvement was seen in some measures, such as the rate of complete disappearance of the tumor at surgery, 17% vs 8%.

Who does this apply to?

This result does not show that radiotherapy is unnecessary in all gastric or esophageal cancers; anatomical location and surgical margins are important. The study's long accrual period and the chemotherapy regimens used must also be taken into account.

What did the researchers want to learn?

After chemotherapy before surgery, is giving chemoradiotherapy after surgery better than giving chemotherapy alone after surgery?

What did this study change?

It cannot be said that postoperative chemoradiotherapy routinely prolongs survival; it provided information about how treatment is distributed before and after surgery.

Benefit for patients

Relevant to patients with gastric cancer after surgery.

What did the research find?

Superiority of postoperative chemoradiotherapy in terms of survival could not be shown; that is, the main goal of the study was not met (median survival 43 months and 37 months; hazard ratio 1.01).

Who does this apply to?

The rate of completing postoperative treatment was low (about 60%); this affects the interpretation of the result.

What did the researchers want to learn?

After gastric surgery performed with extensive lymph node clearance (D2), is CAPOX chemotherapy more beneficial than observation alone?

What did this study change?

It contributed to the development of chemotherapy strategies after high-quality D2 surgery in particular.

Benefit for patients

Relevant to patients who have undergone surgery for gastric cancer.

What did the research find?

With postoperative CAPOX, the time before the disease came back improved; the disease-free rate three years later was 74% vs 59% (hazard ratio 0.56).

Who does this apply to?

The geography in which the study was conducted and the quality of surgery must be taken into account; the results cannot be transferred directly to patients in every country.

What did the researchers want to learn?

After D2 gastric surgery, does S-1, an oral chemotherapy, prolong survival?

What did this study change?

It was decisive in the development of postoperative chemotherapy in East Asia.

Benefit for patients

Relevant to patients who have undergone surgery for gastric cancer (the study population).

What did the research find?

Postoperative S-1 improved survival; the proportion of patients alive three years later was 80.1% vs 70.1%.

Who does this apply to?

The availability of S-1 and the fact that response to the drug differs between populations must be taken into account; the study was conducted in Japan.

What did the researchers want to learn?

In selected advanced gastric cancer with a single cause of spread that surgery alone cannot resolve (liver, peritoneum or lymph nodes around the main vessel), does adding gastric surgery to chemotherapy prolong survival?

What did this study change?

It called into question the benefit of routinely removing the primary tumor in spread gastric cancer, except for symptom control or special circumstances.

Benefit for patients

Relevant to patients with gastric cancer with limited metastases.

What did the research find?

Adding gastric surgery did not improve survival (median 14.3 months and 16.6 months; hazard ratio 1.09); that is, the main goal of the study was not met.

Who does this apply to?

It cannot be generalized to all situations of limited spread; the study covers only specific selected patients.

What did the researchers want to learn?

In advanced gastric or junction cancer that is positive for the protein HER2, is adding trastuzumab to chemotherapy beneficial?

What did this study change?

It showed the importance of HER2 testing and targeted therapy in advanced gastric cancer.

Benefit for patients

Relevant to patients with HER2-positive advanced gastric/GEJ cancer.

What did the research find?

Median survival was 13.8 months in the group with trastuzumab added and 11.1 months in the chemotherapy-alone group (hazard ratio 0.74).

Who does this apply to?

Valid only for patients confirmed to be HER2-positive.

What did the researchers want to learn?

In advanced gastric / gastroesophageal junction (GEJ) / esophageal adenocarcinoma, does adding nivolumab to chemotherapy prolong survival?

What did this study change?

In suitable advanced HER2-negative upper gastrointestinal adenocarcinoma, first-line nivolumab plus chemotherapy (especially with PD-L1 combined positive score [CPS] ≥5) became a standard option.

Benefit for patients

Longer overall survival in selected patients; the benefit varies according to PD-L1 CPS.

What did the research find?

With a PD-L1 combined positive score (CPS) of 5 or higher, median survival was 14.4 vs 11.1 months. With CPS 1 or higher it was 14.0 vs 11.3 months; in all randomized patients it was 13.8 vs 11.6 months. The clearest evidence is in the CPS ≥5 group.

Who does this apply to?

HER2-negative adenocarcinoma. PD-L1 combined positive score (CPS) strata are read separately. It is not confused with perioperative FLOT / MATTERHORN or with esophageal squamous cell carcinoma (CM-648).

What did the researchers want to learn?

In HER2-negative advanced gastric or junction adenocarcinoma, is adding pembrolizumab to chemotherapy beneficial?

What did this study change?

It broadened immunotherapy options in advanced-stage gastric cancer.

Benefit for patients

Relevant to patients with advanced/metastatic gastric or GEJ adenocarcinoma.

What did the research find?

Adding pembrolizumab to chemotherapy improved survival (median 12.9 months and 11.5 months; hazard ratio 0.78).

Who does this apply to?

The absolute benefit may differ according to PD-L1 and other biomarkers; individualized assessment is needed.

What did the researchers want to learn?

In HER2-negative advanced gastric or junction cancer carrying the protein CLDN18.2, is adding zolbetuximab to chemotherapy beneficial?

What did this study change?

It made CLDN18.2 an important test that guides treatment in advanced gastric cancer.

Benefit for patients

Relevant to patients with CLDN18.2-positive advanced gastric/GEJ cancer.

What did the research find?

Benefit was shown in progression-free survival (time before the disease progressed) and overall survival (median progression-free survival 10.61 months and 8.67 months; overall survival 18.23 months and 15.54 months; hazard ratio 0.75 for both).

Who does this apply to?

The test's threshold values and side effects such as nausea and vomiting are important; valid only for CLDN18.2-positive patients.

What did the researchers want to learn?

In CLDN18.2-positive advanced gastric or junction cancer, is zolbetuximab together with CAPOX chemotherapy effective?

What did this study change?

Together with SPOTLIGHT, it strengthened the evidence for CLDN18.2-targeted therapy.

Benefit for patients

Relevant to patients with CLDN18.2-positive advanced gastric cancer.

What did the research find?

Benefit was shown in progression-free survival (time before the disease progressed) and overall survival (median progression-free survival 8.21 months and 6.80 months; overall survival 14.39 months and 12.16 months).

Who does this apply to?

The type of chemotherapy used and differences in side effects must be evaluated. Superiority cannot be inferred by direct comparison with SPOTLIGHT; valid only for CLDN18.2-positive patients.

What did the researchers want to learn?

In HER2-positive advanced gastric cancer previously treated with trastuzumab, is trastuzumab deruxtecan effective?

What did this study change?

It demonstrated the importance of HER2-targeted antibody–drug conjugates in advanced gastric cancer.

Benefit for patients

Relevant to previously treated patients with HER2+ advanced gastric/GEJ cancer.

What did the research find?

The tumor shrinkage (response) rate was reported as 51% vs 14% and median survival as 12.5 months and 8.4 months; superiority over chemotherapy was shown.

Who does this apply to?

The risk of drug-related lung inflammation (interstitial lung disease) must be monitored carefully. The study mainly included Asian patients and its primary endpoint is the tumor response rate.

What did the researchers want to learn?

In HER2-positive advanced gastric cancer that has progressed after trastuzumab, how effective is trastuzumab deruxtecan?

What did this study change?

It provided additional evidence for targeted therapy strategies after prior HER2 therapy.

Benefit for patients

Relevant to previously treated HER2+ gastric/GEJ patients.

What did the research find?

Clinically meaningful tumor responses were shown (confirmed response rate about 42%). There is no comparison (control) group.

Who does this apply to?

Because there is no comparison group, a direct superiority comparison with DESTINY-Gastric01 cannot be made. Valid only for selected HER2-positive patients.

What did the researchers want to learn?

In HER2-positive advanced gastric cancer that has progressed after trastuzumab, does trastuzumab deruxtecan prolong life compared with ramucirumab plus paclitaxel?

What did this study change?

Comparative phase III overall survival evidence for T-DXd in the second line was strengthened; it is not the same design as DESTINY-Gastric01/02.

Benefit for patients

Relevant to patients with HER2-positive advanced gastric/GEJ adenocarcinoma who have previously received trastuzumab.

What did the research find?

Median survival was about 14.7 months vs 11.4 months (hazard ratio [HR] 0.70). The risk of lung inflammation (interstitial lung disease [ILD] / pneumonitis) was higher in the T-DXd arm (~14%).

Who does this apply to?

Only HER2-positive (confirmed after progression). It is not carried over to HER2-negative disease. ILD monitoring is critical. No gold star was awarded.

What did the researchers want to learn?

In previously untreated HER2-positive advanced gastric / gastroesophageal junction (GEJ) cancer, are regimens containing zanidatamab better than trastuzumab plus chemotherapy?

What did this study change?

Phase III progression-free survival (PFS) evidence (and overall survival [OS] for the triplet) for zanidatamab-containing regimens in first-line HER2-positive GEA; there is US FDA approval from August 2026, and the indication is separated by HER2 / immunohistochemistry (IHC) status. Not to be confused with HERIZON-BTC (biliary).

Benefit for patients

Relevant to patients with previously untreated HER2-positive advanced gastroesophageal adenocarcinoma.

What did the research find?

In the first peer-reviewed analysis of the HERIZON-GEA-01 study, median time without disease progression (progression-free survival) was 12.4 months in the two zanidatamab-containing treatment arms and 8.1 months in the standard trastuzumab arm. In the zanidatamab plus tislelizumab plus chemotherapy arm, overall survival was also prolonged. In the zanidatamab plus chemotherapy arm alone, the difference in survival was not statistically significant in the first analysis. In longer follow-up results announced at the ESMO 2026 congress, an overall survival advantage was also reported for this arm; this new analysis has not yet been published in a peer-reviewed journal.

Who does this apply to?

There is no PD-1 inhibitor in the control arm. Direct superiority over the KEYNOTE-811 regimen (trastuzumab + pembrolizumab + chemotherapy) has not been proven. In the United States there are two separate FDA indications according to HER2 / IHC. Diarrhea, heart function, infusion reactions and (with tislelizumab) immune-related side effects are important; symptoms should be reported to the treatment team. Licensing / reimbursement in Turkey (SGK) has not been verified. No gold star was awarded.

What did the researchers want to learn?

In operable gastric cancer, does adding pembrolizumab to chemotherapy improve outcomes?

What did this study change?

Negative / protocol-target-missing perioperative immunotherapy evidence: an increase in pathological complete response (pCR) on its own does not establish a survival standard. It is not equivalent to MATTERHORN.

Benefit for patients

Relevant to interpreting perioperative IO evidence in patients with locally advanced, resectable gastric/GEJ adenocarcinoma.

What did the research find?

The rate of complete disappearance of the tumor at surgery increased (~13% vs ~2%). However, event-free survival did not meet the protocol success threshold; no significant superiority was shown in overall survival.

Who does this apply to?

Higher pCR does not equal better overall survival (OS). MATTERHORN (durvalumab + FLOT) results are not carried over to this card. No gold star is awarded.