Evolving Perioperative Treatment Landscape for Resectable Gastric and Gastroesophageal Junction Cancers: A Q&A with Dr Nataliya Uboha

Despite being uncommon in the United States, gastric and gastroesophageal junction cancers (GC/GEJC) are among the most aggressive gastrointestinal malignancies, often evading detection until the disease has reached an advanced stage.^1-4 These cancers are not routinely screened in the United States and difficult to diagnose early.^3,4 As a result, most oncologists and primary care providers encounter these cancers infrequently, and usually when patients are already experiencing significant symptoms due to advanced disease.⁴ With the US projected to see more than 31,000 new cases of gastric cancer and nearly 11,000 deaths in 2026, these statistics underscore the clinical importance of early detection.^5,6

Adenocarcinoma is the most common histology amongst upper gastrointestinal (GI) cancers in the US, accounting for 75-90% of total cases of GC/GEJC.^1,2,7 Therefore, treatment approaches to gastroesophageal (GEJ) and gastric adenocarcinoma are similar, despite anatomic variability in the primary site.^1,2

Given the challenging nature of this disease, there has been a significant unmet need for more treatment options, including in patients who are diagnosed in the resectable setting and treated with curative intent. ^1-3 Even in the earlier setting, recurrence remains a major challenge: as many as 61% of patients with resectable gastric or GEJ cancer experience disease recurrence.^8,9 Over time, progress has been made, particularly in the perioperative treatment space, and now we have another perioperative treatment option for patients with resectable GC/GEJC available.¹⁰

In the following Q&A, Cancer Network speaks with Dr Nataliya Uboha, a gastrointestinal medical oncologist and faculty leader for the Early Phase Oncology Therapeutics program at the University of Wisconsin Carbone Cancer Center, about the complexity of diagnosing and managing resectable GC/GEJC, the practical integration of the regimen for this patient population, and what this treatment option means for patients and oncologists treating them.

Q1: What makes GC/GEJC difficult to diagnose, and what types of patient presentations have you seen in your practice?

Uboha: Diagnosing these cancers is often challenging in clinical practice, as patients can present with non-specific symptoms or symptoms that are typically seen in benign gastrointestinal conditions, such as gastroesophageal reflux disease (GERD).^11,12,13 This is particularly common for patients with GC/GEJC, who frequently present with heartburn symptoms and then are treated conservatively with acid-suppressive therapy for acid reflux.^12,13 For gastric cancer, patients tend to present with gradual onset of early satiety, unintentional weight loss, and iron deficiency anemia.^1,11

As these symptoms persist and/or progress, patients are referred to a gastroenterologist for further workup and testing.^11,12,14 Diagnosis is typically made during an endoscopy procedure, which then prompts referral to oncology clinics for further management.^11,12,14 By the time these cancers are diagnosed during endoscopy, the disease is often already advanced, a pattern reflected in data showing that more than half of patients are ultimately diagnosed at an advanced stage.^4,11,14

Because GC/GEJC is relatively uncommon in the US, there are no standard screening procedures in place as there are for colorectal cancer, for instance.^4,11,12 That makes it especially important for patients and providers to pay attention when symptoms persist or do not respond to typical treatment.^11,12

Q2: How are resectable GC/GEJC currently treated, and what strategies are emerging to address the risk of recurrence?

Uboha: In practice, our primary goal for resectable and localized adenocarcinomas is curative-intent treatment, but that path is not always straightforward.^9,11,12 After diagnosis, careful staging is of utmost importance to determine whether a patient’s tumor is resectable.^11,12,15,16 Evaluation with endoscopy, imaging, and sometimes diagnostic laparoscopy is needed to determine surgical eligibility and guide treatment planning.^11,12,15,16

If the tumor is considered resectable, we know surgery alone often is not enough.^9,14 Multimodal approaches have been our standard for many years, and clinicians now have another perioperative option for appropriate patients with resectable GC/GEJC.^10,16,17

Prior to this additional perioperative treatment option, resectable GC/GEJC has typically been treated with a combination of surgery and chemotherapy.^16-18 Clinical trials, such as FLOT4, which compared perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy with older perioperative chemotherapy regimens in patients with GC/GEJC, and the ESOPEC Phase III trial, which studied perioperative FLOT chemotherapy versus neoadjuvant chemoradiotherapy in esophageal/GEJC, have helped establish perioperative chemotherapy as a standard of care for patients with resectable gastric, esophageal and GEJ cancers.^18,19 The most common chemotherapy regimen has historically been the FLOT chemotherapy regimen, which consists of 5-fluorouracil (5-FU), leucovorin, oxaliplatin, and docetaxel.^18,19

As mentioned, an important development has been the addition of immunotherapy to perioperative treatment with the approval of IMFINZI® (durvalumab) in combination with FLOT for adult patients with resectable GC/GEJC in late 2025.^10,20 Specifically, IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is approved for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).¹⁰

SELECT SAFETY INFORMATION FOR IMFINZI

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune-mediated dermatologic reactions, and solid organ transplant rejection. IMFINZI can cause severe or life-threatening infusion-related reactions. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody.

Advise women not to become pregnant or breastfeed during treatment with IMFINZI and for 3 months after the last dose.

The most frequent serious adverse reactions (≥2%) in patients with resectable GC/GEJC receiving IMFINZI in combination with FLOT chemotherapy in the MATTERHORN study were diarrhea (2.5%) in the neoadjuvant phase and pneumonia (2.5%) in the adjuvant phase. In patients with GC/GEJC in the adjuvant phase of the MATTERHORN study receiving IMFINZI alone, serious adverse reactions occurred in 14% of patients.

In patients with resectable GC/GEJC, the most common adverse reactions in the overall study (occurring in ≥20% of patients) were diarrhea, nausea, peripheral neuropathy, fatigue, alopecia, decreased appetite, rash, abdominal pain, vomiting, musculoskeletal pain, pyrexia, and stomatitis.

The safety and effectiveness of IMFINZI has not been established in pediatric patients.

Please refer to the Important Safety Information included below and the full Prescribing Information, including Medication Guide, for IMFINZI.

Q3: Could you provide an overview of the durvalumab-based perioperative regimen?

Uboha: For appropriate patients with resectable GC/GEJC, the durvalumab-based regimen—also referred to as D-FLOT (perioperative durvalumab + FLOT followed by adjuvant durvalumab alone)—is delivered across three main phases.¹⁰ Durvalumab is a programmed death-ligand 1 (PD-L1) blocking antibody, and this approach integrates durvalumab both before and after surgery.¹⁰ The regimen begins with up to two cycles of neoadjuvant durvalumab 1500 mg IV every 4 weeks given concurrently with standard FLOT chemotherapy.^10,21 This is followed by curative-intent surgery.¹⁰ After surgery, patients receive up to two additional cycles of durvalumab 1500 mg IV every 4 weeks plus FLOT in the adjuvant setting, and then continue with durvalumab monotherapy 1500 mg IV every four weeks for up to ten cycles.¹⁰

Q4: This perioperative regimen was approved based on results from the MATTERHORN Phase III trial. Can you summarize the trial design and what the final overall survival analysis showed for this patient population?

Uboha: The MATTERHORN trial was a Phase III, randomized study evaluating D-FLOT (perioperative durvalumab + FLOT followed by adjuvant durvalumab alone) versus perioperative FLOT alone in adults with resectable GC/GEJC.^10,20 The primary endpoint was event-free survival (EFS),* with overall survival (OS) as a secondary endpoint.^10,20

The EFS results were based on a planned interim analysis.^10,21 In the trial, patients treated with D-FLOT experienced a 29% reduction in the risk of disease progression, recurrence, or death compared to those who were treated with perioperative FLOT alone (based on an EFS hazard ratio [HR] of 0.71; 95% confidence interval [CI] 0.58-0.86; p<0.001).^10,21 The estimated median EFS for those treated with D-FLOT was not reached (95% CI, 40.7-NE) versus 32.8 months for those treated with perioperative FLOT alone.¹⁰ The median duration of follow-up was 31.5 months (IQR: 26.7-36.6).^10,21

In the final OS analysis, D-FLOT resulted in a statistically significant and clinically meaningful 22% reduction in the risk of death compared to perioperative FLOT alone (HR=0.78 [95% CI, 0.63-0.96]; p=0.021).^10,22 Median OS was not reached in either arm: not reached with D-FLOT (95% CI, NE-NE) and not reached with perioperative FLOT alone (95% CI, NE-NE).^10,22 The OS rate at 3 years was 68.6% in patients treated with D-FLOT and 61.9% in patients treated with FLOT only.^10,22 Follow-up was similar between the two groups, with a median duration of 43.0 months for D-FLOT (range: 3.4-57.0) and 42.9 months for perioperative FLOT alone (range: 0.0-56.5).^10,22

Overall, these findings support adding durvalumab to perioperative management for this patient population (ie perioperative durvalumab + FLOT followed by adjuvant durvalumab alone) and represent an important advancement in our ability to treat resectable GC/GEJC.^20-22

Q5: What does the durvalumab-based regimen mean for patients with resectable GC/GEJC and how oncologists treat these cancers?

Uboha: For eligible patients with resectable GC/GEJC, the availability of the D-FLOT regimen represents a paradigm shift in perioperative treatment.^10,20 Historically, recurrence rates have remained high in this patient population, with as many as 61% of patients with resectable gastric or GEJ cancer experiencing disease recurrence.^3,8,9

The National Comprehensive Cancer Network® (NCCN®) recommends durvalumab and FLOT as a treatment option for patients with resectable GC/GEJC adenocarcinoma.^23,24†Specifically, durvalumab (IMFINZI®) and FLOT as neoadjuvant and adjuvant treatment after surgery, followed by single-agent durvalumab, is an NCCN Category 1, preferred treatment option for PD-L1 with a combined positive score (CPS) of ≥1 or tumor area positive (TAP) of ≥1% in resectable GC/GEJC adenocarcinoma and a Category 2B, preferred option for PD-L1 CPS <1 or TAP <1% resectable GC/GEJC adenocarcinoma.^20,23,24†

For eligible patients, D-FLOT offers a perioperative treatment option shown to reduce the risk of recurrence and improve survival.^10,20,22 For oncologists, it provides another perioperative option for appropriate patients with resectable GC/GEJC.^10,20

Q6: What are some practical considerations oncologists should be aware of when prescribing D-FLOT for their appropriate patients?

Uboha: When prescribing D-FLOT as perioperative therapy for resectable GC/GEJC, patient selection is critical. Appropriate adult candidates should have resectable GC/GEJC.¹⁰

Patient education is another area of focus that can help empower eligible patients and may improve engagement throughout the treatment course. I spend time explaining the importance of perioperative systemic therapy, why we are adding immunotherapy now, what to expect during each phase, and the importance of ongoing communication between patients and their providers. Regular monitoring through labs and clinic visits is key, especially during transitions between therapy phases.¹⁰ It is also vital to teach patients about potential immune-related side effects and encourage them to report any new or worsening symptoms promptly.¹⁰

Patient advocacy groups, such as Debbie’s Dream Foundation, the Gastric Cancer Foundation and Hope for Stomach Cancer, also play a valuable role in supporting individuals with gastric and GEJ cancers. These organizations provide patients with educational resources and peer support networks throughout the treatment process. I often encourage my patients to connect with these groups, as they offer a community of people who truly understand what they're going through and can provide emotional support that complements the medical care we provide.

Finally, successful use of D-FLOT in patients with resectable GC/GEJC requires strong multidisciplinary collaboration among medical oncology, surgery, gastroenterology, and nutrition.^16,17,21 In my practice, frequent tumor board discussions help coordinate care, support smooth transitions from neoadjuvant therapy to surgery and adjuvant treatment, and may help the team identify and address complications or adverse reactions.

Q7: Looking ahead, what gives you the most optimism about the future of care for patients with resectable GC/GEJC?

Uboha: I’m genuinely hopeful about where the field is headed. For eligible patients with resectable GC/GEJC, D-FLOT represents important progress as the first [and only] FDA-approved perioperative immunotherapy-based regimen as a treatment option in this curative intent setting.^10,20-22 I’m also encouraged by the growing collaboration between community clinicians and specialty centers, which can help patients receive care closer to home, while still benefiting from specialty input and clinical expertise. As we continue to raise awareness, improve recognition of symptoms and support earlier referrals, we have an opportunity to diagnose more patients sooner and to potentially improve outcomes.

There is still much work to be done, especially in early detection and reducing recurrence. But with continued partnership, education, and research from trials like MATTERHORN, I believe we will keep making progress for patients.

I’m inspired every day by the strength patients bring to the clinic, and their resilience motivates me to keep advancing care through earlier diagnosis, more treatment options, and close collaboration across the care team.

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI^® (durvalumab).

Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis
IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.

Immune-Mediated Colitis
IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.

Immune-Mediated Hepatitis
IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.

Immune-Mediated Endocrinopathies

• Adrenal Insufficiency: IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
• Hypophysitis:IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
• Thyroid Disorders:IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
  • Thyroiditis: Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI.
  • Hypothyroidism: Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
• Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.

Immune-Mediated Nephritis with Renal Dysfunction
IMFINZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.

Immune-Mediated Dermatology Reactions
IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L1. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.

Other Immune-Mediated Adverse Reactions
The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or were reported with the use of other immune-checkpoint inhibitors.

• Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
• Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
• Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
• Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
• Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica.
• Endocrine: Hypoparathyroidism.
• Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
• Other: Myocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap Syndrome, reported as the co-occurrence of either two or all three adverse reactions

Infusion-Related Reactions
IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.

Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity
Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and advise them to use effective contraception during treatment with IMFINZI and for 3 months after the last dose of IMFINZI.

Lactation
There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for 3 months after the last dose.

Adverse Reactions

• In patients with resectable GC/GEJC, the most common adverse reactions in the overall study (occurring in ≥20% of patients) were diarrhea, nausea, peripheral neuropathy, fatigue, alopecia, decreased appetite, rash, abdominal pain, vomiting, musculoskeletal pain, pyrexia, and stomatitis.
• In patients with resectable GC/GEJC in the neoadjuvant phase of the MATTERHORN study receiving IMFINZI in combination with FLOT chemotherapy (n=475), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 2.5% of patients. Serious adverse reactions occurred in 21% of patients; the most frequent (≥2%) serious adverse reaction was diarrhea (2.5%). Deaths occurred in 1.9% of patients; deaths of ≥2 patients included septic shock (0.6%) and acute coronary syndrome (0.4%). Of the 475 patients in the IMFINZI + FLOT chemotherapy treatment arm and 469 patients in the placebo + FLOT chemotherapy treatment arm who received neoadjuvant treatment, 0.6% and 0.4% of patients, respectively, did not receive surgery due to adverse reactions, and 2.3% and 2.6% of patients, respectively, had a delay in surgery due to ARs.
• In patients with resectable GC/GEJC in the adjuvant phase of the MATTERHORN study receiving IMFINZI in combination with FLOT chemotherapy (n=365), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 7% of patients. Serious adverse reactions occurred in 29% of patients; the most frequent (≥2%) serious adverse reaction was pneumonia (2.5%). Deaths occurred in 2.2% of patients; deaths of ≥2 patients included gastrointestinal perforation (0.5%) and COVID-19 (0.5%).
• In patients with resectable GC/GEJC in the adjuvant phase of the MATTERHORN study receiving IMFINZI alone (n=345), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6% of patients. Serious adverse reactions occurred in 14% of patients. Deaths occurred in 1.7% of patients; deaths of ≥2 patients included gastrointestinal perforation (0.6%) and COVID-19 (0.6%).

The safety and effectiveness of IMFINZI has not been established in pediatric patients.

Indication:

IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

Please see Full Prescribing Information including Medication Guide for IMFINZI.

*EFS was defined as the time from randomization to the following, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per blinded independent central review (BICR) assessment and/or locally by pathology testing: Progression that precludes surgery or requires non-protocol therapy; local or distant recurrence or progression of disease; or death due to any cause.¹⁸

^†See the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for detailed recommendations, including other preferred treatment options.

References

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9. Liu D, Lu M, Li J, et al. The patterns and timing of recurrence after curative resection for gastric cancer in China. World J Surg Oncol. 2016;14(1):305.
10. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026.
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13. Medicine Net. Gastroesophageal Reflux Disease (GERD). Accessed June 2026. Available at: https://www.medicinenet.com/gastroesophageal_reflux_disease_gerd/article.htm
14. Medicine Net. Gastroesophageal junction adenocarcinoma. Accessed June 2026. Available at: https://www.medicinenet.com/gastroesophageal_junction_adenocarcinoma/article.html
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18. Al-Batran SE, Homann N, Pauligk C, et al; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393(10184):1948-1957.
19. Hoeppner J et al. Perioperative chemotherapy or preoperative chemoradiotherapy in esophageal cancer. N Engl J Med. 2025;392(4):323-335.
20. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal cancer. N Engl J Med. 2025;393(3):217-230.
21. Janjigian YY et al. Event-free survival (EFS) in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). Presented at the American Society of Clinical Oncology. Chicago, United States. June 1, 2025.
22. Tabernero J, Al-Batran SE, Wainberg ZA, et al. Final overall survival and the association of pathological outcomes with event-free survival in MATTERHORN: a randomised, Phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel in resectable gastric / gastroesophageal junction adenocarcinoma. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Session LBA81.
23. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.3.2026. ©National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed June 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
24. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers V.3.2026. ©National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed June 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

US-114093 Last Updated 7/26