Durvalumab Earns Priority Review, Breakthrough Status in Gastric Cancer

In the trial, durvalumab with FLOT exhibited superior EFS outcomes vs placebo plus FLOT in patients with gastric and GEJ cancers at not reached (NR; 95% CI, 40.7-NR) and 32.8 months (95% CI, 27.9-NR), respectively.

The FDA has granted priority review and breakthrough therapy designation to durvalumab (Imfinzi) for the treatment of patients with resectable, early-stage, and locally advanced gastric and gastroesophageal junction (GEJ) cancers, according to a news release from the drug’s developer, AstraZeneca.1

The FDA has assigned a Prescription Drug User Fee Act date in the fourth quarter of 2025 for approving durvalumab in this patient population.

The agency’s decision is supported by findings from the phase 3 MATTERHORN trial (NCT04592913) previously published in the New England Journal of Medicine and presented during a plenary session at the 2025 American Society of Clinical Oncology Annual Meeting.2,3

In the trial, durvalumab with 5-fluorouracil, leucovorin (folinic acid), oxaliplatin, and docetaxel (FLOT) exhibited superior event-free survival (EFS) outcomes vs placebo plus FLOT in patients with gastric and GEJ cancers. The median EFS was not reached (NR; 95% CI, 40.7-NR) and 32.8 months (95% CI, 27.9-NR), respectively (HR, 0.71; 95% CI, 0.58-0.86; P < .001), with 18- and 24-month EFS rates of 73% vs 64% and 67% vs 59%.

Additional efficacy data showed that disease-free survival (DFS) outcomes also favored durvalumab plus FLOT vs FLOT alone. The median DFS was NR (95% CI, NR-NR) with durvalumab vs 39.8 months (95% CI, 38.7-NR) with placebo (HR, 0.70; 95% CI, 0.53-0.93). The respective 18- and 24-month DFS rates were 79% vs 73% and 75% vs 66%.

Furthermore, an overall survival (OS) trend favored durvalumab (HR, 0.78; 95% CI, 0.62-0.97; P = .025).

“This priority review reinforces the potential for a perioperative approach with [durvalumab] to transform care for patients with early gastric and [GEJ] cancers who frequently [have] disease recurrence or progression even after curative-intent surgery and perioperative chemotherapy. This novel treatment is the only immunotherapy-based regimen to show a statistically significant reduction in the risk of progression, recurrence, or death in this setting and, if approved, is poised to change the clinical paradigm,” Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, said in the news release.1

Patients with stage II to IVA gastric or GEJ adenocarcinoma with no evidence of metastasis or prior therapy were randomly assigned 1:1 to receive durvalumab at 1500 mg every 4 weeks and FLOT (n = 474) or placebo plus FLOT (n = 474). Patients were stratified by region, node positivity, and PD-L1 expression. In the neoadjuvant phase, durvalumab or placebo was given with FLOT for 2 cycles before surgery. In the adjuvant phase, an additional 2 cycles of the aforementioned regimens were administered and followed by 10 cycles of durvalumab at 1500 mg every 4 weeks or placebo.

In the durvalumab and placebo arms, the median age was 62 years (range, 26-84) vs 63 years (range, 28-83). A total of 69% vs 75% of the respective arms were men, 81% vs 81% were not from Asia, and 71% vs 77% had an ECOG performance score of 0. The most common tumor site was gastric (68% vs 67%), most patients had non-T4 cancer (75% vs 75%), and most had node-positive status (69% vs 70%). Furthermore, most patients had a PD-L1 expression of 1% or greater (90% vs 90%), intestinal histology (52% vs 50%), and cancer that was not microsatellite instability high (64% vs 65%).

The primary end point of the trial was EFS. Secondary end points included OS, pathologic complete response, DFS, and safety.

In the investigational and control arms, 99% vs 99% experienced any-grade adverse effects (AEs), with 95% vs 95% considered possibly related to treatment. The incidence of grade 3 or 4 AEs was 72% vs 71% in the respective arms, with 60% vs 59% considered possibly related to study treatment. Serious AEs occurred in 48% vs 44% of patients.

AEs leading to treatment discontinuation occurred in 30% of the durvalumab arm vs 23% of the placebo arm, with 10% vs 6% considered related to the investigational or control agents. AEs resulting in death occurred in 5% vs 4% of the respective arms, with 1% and less than 1% considered possibly related to durvalumab or placebo, respectively.

According to developers, regulatory applications are currently under review in the EU and Japan, among other countries, based on the phase 3 MATTERHORN trial results.

References

1. IMFINZI (durvalumab) granted priority review and breakthrough therapy designation in the US for patients with resectable early-stage gastric and gastroesophageal junction cancers. News release. AstraZeneca. July 28, 2025. Accessed July 28, 2025. https://tinyurl.com/bdvtxze3
2. Janjigian YY, Al-Batran SE, Wainberg Z, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med. 2025;393(3):217-230. doi:10.1056/NEJMoa2503701
3. Janjigian Y, Al-Batran SE, Wainberg Z, 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). J Clin Oncol. 2025;43(suppl 17):LBA5. doi:10.1200/JCO.2025.43.17_suppl.LBA5