Andrea Eleazar, MHS

Among patients with gastric/gastroesophageal junction (G/GEJ) adenocarcinoma that is resectable, Imfinzi with FLOT improved survival.

Among patients with gastric/gastroesophageal junction (G/GEJ) adenocarcinoma that is resectable, or removable by surgery the combination of the anti-PD-L1 monoclonal antibody Imfinzi (durvalumab) with the FLOT (5-fluorouracil-leucovorin-oxaliplatin-docetaxel) chemotherapy regimen was associated with a significant and clinically meaningful improvement in overall survival, or the time patients live after treatment, when compared to placebo plus FLOT.

These findings, which were regardless of pathological status, were shared in a presentation of data from the phase 3 MATTERHORN trial at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.

With a data cutoff date of Sept. 1, 2025, the final overall survival analysis of the intention-to-treat population yielded a hazard ratio (HR) of 0.78 comparing the investigational arm with the control arm, with median OS not reached in either arm.

 The length of time from the start of treatment or diagnosis that patients in a study are still alive.

 The length of time patients remain alive without certain events occurring, such as the cancer coming back, progressing, or death from any cause.

 This means that when the tissue removed during surgery is examined under a microscope, no signs of invasive cancer are found.

“The overall survival results of the MATTERHORN study strongly support the use of Imfinzi plus chemotherapy with FLOT as a new global standard of care for patients with localized, [resectable, G/GEJ] adenocarcinoma,” said Dr. Josep Tabernero, professor of medicine, head, Department of Medical Oncology, Vall d’Hebron University Hospital, and director of Vall d’Hebron Institute of Oncology, Barcelona, Spain, in his presentation.

Furthermore, a survival analysis stratified by demographic and clinical characteristics showed that OS improvement was consistent across most key subgroups. Notably, a similar improvement in OS was achieved regardless of PD-L1 status. In patients who were PD-L1-positive, the HR was 0.79, and the HR was 0.79 in patients who were PD-L1-negative, even demonstrating identical HRs across groups.

Additional findings reported included an improvement in event-free survival (EFS), the study’s primary end point, among patients with any degree of pathological response and regardless of pathological nodal status at the time of the data cutoff on Dec. 20, 2024.

What Are the Study Design and Patient Characteristics?

The phase 3 MATTERHORN trial is a global, randomized, double-blind, placebo-controlled study evaluating the efficacy of neoadjuvant-adjuvant durvalumab plus FLOT chemotherapy. The study’s primary end point is EFS; key secondary end points include OS and pathological complete response (pCR).

The study population consists of 948 patients with localized G/GEJ adenocarcinoma who were treatment-naive upon enrollment. Patients were enrolled from across Asia, Europe, North America and South America; of note, according Tabernero, is that 20% of patients were from Asia. Patients were stratified by geographical region, clinical lymph node status and PD-L1 expression.

For treatment, patients were randomly assigned to receive either the Imfinzi and FLOT combination or placebo plus FLOT (474 patients, both arms) in the neoadjuvant setting. Here, patients received their 1500 mg of their assigned treatment plus FLOT for two cycles before undergoing surgical resection four to eight weeks after their last dose. Following surgical resection recovery, patients received 1500 mg of durvalumab or placebo as adjuvant therapy for up to one year.

What Trial Data Have Been Previously Reported?

In 2023, interim results with a data cutoff on Feb. 1, 2023 suggested a significant and clinically meaningful benefit in pCR and near-PCR, with response rates of 27% and 14% observed in the investigational and control arms, respectively. Next, earlier in 2025, results of a primary end point analysis published in 

 revealed a two-year EFS rate of 67.4% in the investigational arm versus 58.5% in the control arm. A consistent and manageable safety profile between arms was depicted in both reports.

Riding on the favorable efficacy and safety trends observed in previous analyses, this most recent readout highlights the potential of durvalumab and FLOT to become a new perioperative treatment option for patients.

“Final overall survival (OS) and the association of pathological outcomes with event-free survival (EFS) in MATTERHORN: A randomised, phase III study of durvalumab (D) plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric / gastroesophageal junction (G / GEJ) adenocarcinoma.” by Dr. Josep Tabernero. Presented at: ESMO 2025 Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA81.

“Assessing durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer;” 

https://clinicaltrials.gov/study/NCT04592913

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Articles

The combination of Imfinzi (durvalumab) with FLOT chemotherapy significantly improves overall survival in patients with resectable gastric/gastroesophageal junction adenocarcinoma compared to placebo plus FLOT. The phase 3 MATTERHORN trial demonstrated consistent survival benefits across various subgroups, including PD-L1 status. The trial's primary endpoint, event-free survival, also showed improvement. The study involved 948 treatment-naive patients globally, with a notable 20% from Asia. Interim results indicated significant pathological complete response rates, and the treatment maintained a consistent safety profile, suggesting its potential as a new perioperative standard of care.

Imfinzi Plus Chemo Improves Survival in G/GEJ Adenocarcinoma

Combining Tecentriq with BCG therapy did not lead to better outcomes compared with BCG alone: © stock.adobe.com.

Combining Tecentriq (atezolizumab) with Bacillus Calmette-Guérin (BCG) therapy did not lead to better outcomes compared with BCG alone for patients with high-risk, non–muscle-invasive bladder cancer (NMIBC) who had not previously received BCG treatment. These findings, shared at the 2025 European Society for Medical Oncology (ESMO) Congress, showed that the addition of Tecentriq did not significantly improve the time patients lived without their cancer returning or worsening.

The findings, presented by Dr. Morgan Roupret, professor of urology at Sorbonne University in Paris, France, and simultaneously published in the 

, reported 73 events of 262 patients in the experimental combination arm versus 72 of 255 patients in the single-agent BCG arm. Events were defined as high-grade or low-grade NMIBC relapse, persistence of carcinoma in situ (CIS) after 6 months, progression of disease, appearance of upper tract urothelial carcinoma, or death of any cause.

“You don’t have to be a statistician to see the [Kaplan-Meier] curves are very close to one another,” Roupret said during the presentation.

Regarding the secondary end point of high-grade recurrence-free survival (RFS), defined as reappearance of high-grade NMIBC or death of any cause, there was also no improvement in the experimental arm. Data were not yet mature for an analysis of overall survival (OS), but there was no impact on the median survival with the addition of Tecentriq.

Side Effects Associated With Tecentriq and BCG Combination

Any-grade treatment-related side effects were reported in 94% (240 patients) and 76% (189 patients) of patients in the experimental and control arms, respectively. Grade 3 or higher and serious side effects occurred in 23% (58 patients) of those receiving Tecentriq and 9% (22 patients) of those receiving BCG only, and in 24% (60 patients) and 8% (21 patients) of patients, respectively.

Side effects leading to dose interruption occurred in 18% (47 patients) of the experimental arm versus 8% (9 patients) of the control arm. Treatment withdrawal due to side effects occurred in 29% (73 patients) and 9% (22 patients) of patients, respectively. In the experimental arm, 13% (32 patients) withdrew from BCG only, 16% (41 patients) withdrew from Tecentriq only, and 3% (8 patients) withdrew from both.

“Side effects such as rash and pruritus were common and consistent with previously published data. There was no particular surprise,” Roupret said.

How the ALBAN Trial Evaluated Tecentriq Plus BCG in High-Risk Bladder Cancer

The ALBAN study enrolled 517 patients who were BCG-naive with high-risk NMIBC after first- and second-look transurethral resection of bladder tumor (TURBT). High risk was defined as the presence of any high-grade or grade 3 Ta or T1 tumors and/or CIS. Patients were also required to have no metastatic disease in the pelvis, abdomen, or chest and an ECOG performance status of 0 to 2.

Patients were randomized 1:1 to receive BCG once a week for 6 weeks during the induction phase and once a week for 3 weeks at 3, 6, and 12 months during the maintenance phase, with or without Tecentriq, which was administered at 1200 mg intravenously every 3 weeks for up to 1 year.

The primary end point was EFS, and key secondary end points included high-grade RFS, progression-free survival, OS, duration of response, safety, and quality of life.

Understanding the ALBAN Study Population in High-Risk NMIBC

Patient characteristics were balanced between the treatment arms. The median age was 68 years in the combination arm versus 67 years in the control arm. Male patients comprised 84% (221 patients) of the experimental arm and 87% (221 patients) of the control arm.

Roupret noted that the only notable discrepancy between arms was smoking history. In the experimental arm, 66% (173 patients) identified as former smokers and 19% (50 patients) as current smokers. In the control arm, 62% (157 patients) were former smokers and 15% (38 patients) were current smokers.

What’s Next for NMIBC Treatment After the ALBAN Trial?

Roupret concluded that future research will focus on biomarker-driven patient selection based on integrated molecular and spatial immune profiling. He also emphasized the need to optimize the timing, duration, and delivery route of checkpoint inhibitors in NMIBC.

"ALBAN: A phase 3, randomized, open-label, international study of intravenous (IV) atezolizumab and intravesical Bacillus Calmette-Guérin (BCG) vs BCG alone in BCG-naïve high-risk, non-muscle-invasive bladder cancer (NMIBC)," by Dr. Morgan Roupret. Presented at: ESMO 2025 Congress; Oct. 17–20, 2025; Berlin, Germany. Abstract LBA107.

"ALBAN (GETUG-AFU 27): A phase 3, randomized, open-label, international trial of intravenous atezolizumab and intravesical Bacillus Calmette-Guérin (BCG) versus BCG alone in BCG-naïve high-risk, non-muscle invasive bladder cancer (NMIBC)," by Dr. Morgan Roupret. 

The combination of Tecentriq (atezolizumab) with Bacillus Calmette-Guérin (BCG) therapy did not improve outcomes for high-risk, non–muscle-invasive bladder cancer (NMIBC) patients compared to BCG alone. The ALBAN trial, presented at the 2025 ESMO Congress, showed no significant difference in event-free survival or high-grade recurrence-free survival between the two groups. Side effects were more prevalent in the combination arm, leading to higher rates of treatment withdrawal. Future research will focus on biomarker-driven patient selection and optimizing checkpoint inhibitor use in NMIBC.

The addition of Tecentriq to BCG therapy did not significantly improve outcomes for patients with non–muscle-invasive bladder versus BCG alone.

Andrea Eleazar, MHS

Imfinzi Plus Chemo Improves Survival in G/GEJ Adenocarcinoma

Tecentriq Plus BCG Does Not Improve Outcomes in Some With Bladder Cancer

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