Treatment with the anti–PD-L1 monoclonal antibody durvalumab (Imfinzi) plus 5-fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) produced a statistically significant and clinically meaningful improvement in overall survival (OS) among patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma vs placebo plus FLOT, regardless of pathological status, according to results from the phase 3 MATTERHORN trial (NCT04592913) presented during the 

With a data cutoff date of September 1, 2025, the final OS analysis of the intention-to-treat population yielded a hazard ratio (HR) of 0.78 (95% CI, 0.63–0.96; 

 = .021) comparing the investigational arm with the control arm, with median OS not reached in either arm.

“The OS results of the MATTERHORN study strongly support the use of durvalumab plus chemotherapy with FLOT as a new global standard of care for patients with localized, [resectable, gastric/GEJ] adenocarcinoma,” said Josep Tabernero, MD, PhD, professor of medicine, head of the Department of Medical Oncology at 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 (PD-L1 TAP ≥1%), the HR was 0.79 (95% CI, 0.63–0.99), and the HR was 0.79 (95% CI, 0.41–1.50) in patients who were PD-L1-negative (PD-L1 TAP <1%), 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 December 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 gastric/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 1:1 to receive either the durvalumab and FLOT combination or placebo plus FLOT (n = 474, both arms) in the neoadjuvant setting. Here, patients received their 1500 mg of their assigned treatment plus FLOT for 2 cycles before undergoing surgical resection 4 to 8 weeks after their last dose.

 Following surgical resection recovery, patients received 1500 mg of durvalumab or placebo as adjuvant therapy for up to 1 year.

What Trial Data Have Been Previously Reported?

In 2023, interim results with a data cutoff on February 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 2-year EFS rate of 67.4% in the investigational arm vs 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.

Disclosures: Tabernero declared a consulting role with Accent Therapeutics, Alentis Therapeutics, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Carina Biotech, Cartography Biosciences, Chugai Pharmaceutical, Daiichi Sankyo Company, Eli Lilly and Company, F. Hoffmann-La Roche AG, Genentech, Johnson & Johnson, Menarini Ricerche S.p.A, Merus N.V., MSD, Novartis, Ono Pharma USA, Peptomyc, Pfizer, Pierre Fabre, Quantro Therapeutics, Scandion Oncology, Scorpion Therapeutics, Servier, Sotio Biotech, Taiho Pharmaceutical, Takeda Pharmaceutical International AG, and Tolremo Therapeutics, and stocks with 1 TRIAL SP, Alentis Therapeutics, Oniria Therapeutics and Pangaea Oncology.

Tabernero, J. 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. 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. ClinicalTrials.gov. Updated April 3, 2025. Accessed October 17, 2025. 

https://clinicaltrials.gov/study/NCT04592913

Janjigian YY, Van Cutsem E, Muro K, et al. MATTERHORN: phase III study of durvalumab plus FLOT chemotherapy in resectable gastric/gastroesophageal junction cancer. 

. 2022;18(20):2465-2473. doi:10.2217/fon-2022-0093

Janjigian YY, Al-Batran SE, Wainberg Za, et al. LBA73 Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study. 

. 2023;34:S1315-S1316. doi: 10.1016/j.annonc.2023.10.074

Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. 

. 2025;393(3):217-230. doi: 10.1056/nejmoa2503701

Articles

The phase 3 MATTERHORN trial demonstrated that durvalumab combined with FLOT chemotherapy significantly improved overall survival in patients with resectable gastric/gastroesophageal junction adenocarcinoma compared to placebo plus FLOT. This improvement was consistent across various subgroups, including PD-L1 status. The trial's primary endpoint, event-free survival, also showed favorable results. The study involved 948 treatment-naive patients globally, with a balanced distribution between the investigational and control arms. Previous interim results indicated significant benefits in pathological complete response rates, supporting durvalumab plus FLOT as a potential new standard of care.

Saruparib plus an androgen receptor pathway inhibitor was safe and active in metastatic prostate cancer.

Perioperative Durvalumab Plus FLOT Generates OS Benefit in Gastric/GEJ Adenocarcinoma

Atezolizumab and intravesical BCG in NMIBC: 

Atezolizumab (Tecentriq) in combination with BCG induction and maintenance therapy did not produce a significant benefit in terms of event-free survival (EFS) compared with BCG alone for the treatment of patients with BCG-naive, high-risk non–muscle invasive bladder cancer (NMIBC), according to findings from the phase 3 ALBAN trial (NCT03799835) presented during the 

The findings, presented by Morgan Roupret, MD, PhD, 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 vs 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. The HR for EFS was 0.98 (95% CI, 0.71–1.36; 

“You don’t have to be a statistician to see the [Kaplan-Meier] curves are very close to one another,” said Roupret 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 (HR, 1.06; 95% CI, 0.73–1.55; 

= .7658). 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 atezolizumab (HR, 1.73; 95% CI, 0.73–3.92; 

Any-grade treatment-related adverse events (TRAEs) were reported in 94.1% (n = 240) and 75.6% (n = 189) of patients in the experimental and control arms, respectively. Grade ≥3 TRAEs and serious TRAEs occurred in 22.7% (n = 58) of patients in the atezolizumab arm and 8.8% (n = 22) of patients in the BCG-only arm and 23.5% (n = 60) and 8.4% (n = 21) of patients, respectively.

TRAEs leading to dose interruption were reported in 18.4% (n = 47) of patients in the experimental arm vs 7.6% (n = 9) in the control arm; TRAEs leading to withdrawal were reported in 28.6% (n = 73) and 8.8% (n = 22) of patients, respectively. In the experimental arm, 12.5% (n = 32) of patients withdrew from BCG only, 16.1% (n = 41) withdrew from atezolizumab only, and 3.1% (n = 8) withdrew from both.

“[Adverse events] that were depicted, rash and pruritus, were largely common and already depicted in the previous literature. There was no particular surprise,” Roupret said during the presentation.

ALBAN enrolled 517 patients who were BCG-naïve 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/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 atezolizumab, 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.

Patient characteristics were balanced between the arms. The median age was 67.7 years (range, 36.0–88.0) in the combination arm vs 67.0 (range, 29.0–91.0) in the control arm. Male patients comprised 84.4% (n = 221) of the experimental arm and 86.7% (n = 221) of the control arm.

Roupret noted that the only potential discrepancy between arms was past history as a smoker. In the experimental arm, 66.0% (n = 173) of patients identified as a former smoker and 19.1% (n = 50) as a current smoker. In the control arm, these numbers were 61.8% (n = 157) and 15.0% (n = 38), respectively.

In his conclusion, Roupret said that future research would focus on biomarker-driven patient selection based on integrated molecular and spatial immune profiling. He also noted a need for optimization of the timing, duration, and delivery route of checkpoint inhibitors in NMIBC.

Disclosures: Roupret declared a consulting or advisory role with Johnson & Johnson, Ipsen, BMS, Astellas, Accord Healthcare, AAA, Ferring, Oncodiag, Intuitive, Medtronics, MSD, Pfizer, AstraZeneca, Bayer, Photocure, Provepharm, Thermofisher, Vitadx, Recordati, Besins Healthcare, CG Oncology, Curium, and Roche Genentech.

Roupret M. 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). Presented at: ESMO 2025 Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA107.

Roupret M, Bertaut A, Pignot G, et al. 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). 

. Published online October 17, 2025. doi:10.106/j.annonc.2025.09.017

Atezolizumab combined with BCG therapy did not significantly improve event-free survival (EFS) compared to BCG alone in BCG-naive, high-risk non–muscle invasive bladder cancer (NMIBC) patients, as shown in the phase 3 ALBAN trial. The trial reported similar high-grade recurrence-free survival (RFS) and no impact on median overall survival (OS) with the addition of atezolizumab. Safety findings indicated higher treatment-related adverse events in the combination arm. Future research will focus on biomarker-driven patient selection and optimizing checkpoint inhibitor administration in NMIBC.

Atezolizumab plus BCG did not extend EFS vs BCG alone in BCG-naive, high-risk non–muscle invasive bladder cancer.

Atezolizumab Plus BCG Does Not Improve EFS Vs BCG Alone in BCG-Naive NMIBC

Sacituzumab tirumotecan (sac-TMT; SKB264; MK-2870) produced a significant progression-free survival (PFS) benefit vs chemotherapy for the treatment of patients with pretreated locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer, according to data from the  phase 3 OptiTROP-Breast02 trial (NCT06081959) presented during the 

Notably, sac-TMT elicited a 65% reduction in the risk of disease progression or death vs chemotherapy (HR, 0.35; 95% CI, 0.26-0.48; 

 <.0001) and showed a consistent benefit across subgroups. At a median follow-up of 7.4 months, the median PFS (mPFS) in patients receiving sac-TMT (8.3 months; 95% CI, 7.0-8.6) was approximately twice that of patients receiving chemotherapy (4.1 months; 95% CI, 3.0-4.3).

Additionally, an interim analysis of overall survival (OS) revealed a positive trend among those receiving sac-TMT compared to those receiving chemotherapy (HR, 0.33; 95% CI, 0.18-0.61).

“The current chemotherapy options [for HR+/HER2– breast cancer] show limited efficacy,” said Man Li, professor at the Second Affiliated Hospital of Dalian Medical University, during the presentation.

 “Sac-TMT has shown promising activity in pretreated patients with HR+/HER2– metastatic breast cancer in [a] phase 2 study [NCT04152499].”

These new statistically significant and clinically meaningful efficacy data from OptiTROP-Breast02, along with an observed manageable safety profile, strengthen the case for sac-TMT as a potential new treatment option for this patient population who comprise a vast majority of global breast cancer cases.

“The OptiTROP-Breast02 study supports sac-TMT as a new treatment option for patients with HR+/HER2– breast cancer following endocrine-based therapy and chemotherapy,” said Li.

OptiTROP-Breast02 is a global, randomized, open-label study evaluating the efficacy and safety of sac-TMT vs investigator’s choice of chemotherapy (ICC) in adult patients with unresectable, locally advanced or metastatic HR+/HER2– breast cancer who had failed at least 1 line of systemic chemotherapy.

 The study is assessing the primary end point of PFS, along with secondary end points of investigator-assessed OS, objective response rate, disease control rate, and duration of response.

Patients were eligible for participation if they had HR+/HER2– breast cancer, had between 1 and 4 lines of chemotherapy, and had at least 1 endocrine therapy, CDK 4/6 inhibitor, and taxane in any setting. Of 399 patients randomized 1:1 to either the investigational arm (n = 200) or control arm (n = 199), 200 received 5 mg/kg of intravenous sac-TMT every 2 weeks, while 196 received ICC including eribulin, capecitabine, gemcitabine, and vinorelbine.

What Were the Patient Characteristics in the OptiTROP-Breast02 trial?

Patient characteristics were well balanced between the study arms. Across both arms, the median age was 54 years (range, 31-74), two-thirds had an ECOG performance status of 1, about 53% were HER2 zero, and 47% were HER2 low. About 96% of patients had visceral metastases and over three-fourths had liver metastases. About three-fourths of patients had received neoadjuvant chemotherapy and all patients had received prior taxane, endocrine therapy, and a CDK 4/6 inhibitor. About 56% of patients had received at least 2 lines of chemotherapy in the advanced/metastatic setting and a little over one-fourth of patients had primary endocrine resistance.

This most recent report of safety data revealed a manageable safety profile, with no new safety signals. In terms of treatment-related adverse events (TRAEs), the incidence of all-grade and grade ≥3 TRAEs was comparable between investigational and control arms. The most common TRAEs for both sac-TMT and chemotherapy were hematologic toxicities, including decreased white blood cell count, anemia, and neutropenia. While stomatitis was more frequent in patients receiving sac-TMT (63% vs 8%), Li noted that these events were primarily low-grade and manageable.

Treatment discontinuation occurred in 87 and 138 patients in the investigational and control arms, respectively. The most common reason for discontinuation was radiographic disease progression in both the investigational arm (n = 80) and control arm (n = 122).

Regarding next steps Li said, “Phase 3 studies of sac-TMT as a monotherapy and/or in combination with pembrolizumab (Keytruda) in patients with chemotherapy-naïve HR+/HER2– breast cancer are ongoing globally (NCT06312176) and in China (NCT07071337).”

 Li had no interests to declare pertaining to this presentation.

Li, M. Sacituzumab tirumotecan (sac-TMT) vs investigator's choice of chemotherapy (ICC) in previously treated locally advanced or metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer (BC): results from the randomized, multi-center phase 3 OptiTROP-Breast02 study. Presented at: ESMO 2025 Congress; October 17–20, 2025; Berlin Germany. Abstract LBA23.

Study of SKB264 for Locally Advanced, Recurrent or Metastatic HR+/​HER2- Breast Cancer. ClinicalTrials.gov. Updated December 12, 2024. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT06081959

Sacituzumab tirumotecan (sac-TMT) demonstrated a significant progression-free survival (PFS) advantage over chemotherapy in pretreated, locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer, as shown in the phase 3 OptiTROP-Breast02 trial. Sac-TMT reduced the risk of disease progression or death by 65% compared to chemotherapy, with a median PFS of 8.3 months versus 4.1 months. The safety profile was manageable, with hematologic toxicities being the most common adverse events. Ongoing phase 3 studies are exploring sac-TMT as monotherapy and in combination with pembrolizumab.

Sac-TMT bested chemotherapy in terms of PFS in previously treated HR+, HER2– metastatic breast cancer.

Sac-TMT Yields PFS Benefit Over Chemotherapy in Pretreated HR+, HER2– Metastatic Breast Cancer

Durvalumab Plus FLOT in G/GEJ Adenocarcinoma:

Image by Ashling Wahner and MJH Life Sciences Using AI

Durvalumab (Imfinzi) in combination with 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) yielded a significant overall survival (OS) benefit compared with placebo plus FLOT for the treatment of patients with resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma according to findings from the phase 3 MATTERHORN trial (NCT04592913) presented during the 

At the September 1, 2025, data cutoff, the final OS analysis of the intention-to-treat population yielded an HR for OS of 0.78 (95% CI, 0.63–0.96; 

 =.021) comparing the investigational arm with the control arm, with a median OS that was not reached in either arm.

“The OS results of the MATTERHORN study strongly support the use of durvalumab plus chemotherapy with FLOT as a new global standard of care for patients with localized, [resectable, G/GEJ] adenocarcinoma,” said Josep Tabernero, MD, PhD, 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.

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.

In 2023, interim results with a data cutoff on February 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.

Assessing durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer. ClinicalTrials.gov. Updated April 3, 2025. Accessed October 17, 2025. https://clinicaltrials.gov/study/NCT04592913

. 2023;34:S1315-S1316. doi:10.1016/j.annonc.2023.10.074

5.Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. 

. 2025;393(3):217-230. doi:10.1056/nejmoa2503701

Durvalumab combined with FLOT chemotherapy significantly improved overall survival (OS) in patients with resectable gastric/gastroesophageal junction adenocarcinoma, as demonstrated in the phase 3 MATTERHORN trial. The trial's final OS analysis showed a hazard ratio (HR) of 0.78, indicating a survival benefit over placebo plus FLOT. The OS improvement was consistent across key subgroups, including PD-L1 status. The study also reported enhanced event-free survival (EFS) and a manageable safety profile. These findings suggest durvalumab plus FLOT could become a new standard of care for this patient population.

The addition of durvalumab to FLOT prolonged overall survival vs FLOT alone in resectable gastric/gastroesophageal junction adenocarcinoma.

Andrea Eleazar, MHS

Articles

Perioperative Durvalumab Plus FLOT Generates OS Benefit in Gastric/GEJ Adenocarcinoma

Atezolizumab Plus BCG Does Not Improve EFS Vs BCG Alone in BCG-Naive NMIBC

Sac-TMT Yields PFS Benefit Over Chemotherapy in Pretreated HR+, HER2– Metastatic Breast Cancer

Durvalumab Plus FLOT Prolongs OS vs FLOT Alone in Gastric/GEJ Adenocarcinoma