AZ piles pressure on MSD et al in gastric cancer

AstraZeneca's cancer immunotherapy Imfinzi has been approved in the EU for use before and after surgery for early-stage gastric cancer, consolidating its position in the disease after picking up approval in the US toward the end of last year.

The green light is for two cycles of PD-L1 inhibitor Imfinzi (durvalumab) in combination with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy, given in the neoadjuvant (pre-surgery) and adjuvant (post-surgery) settings, followed by Imfinzi monotherapy as a maintenance therapy.

The approval is based on the MATTERHORN trial, which involved patients with stage II, III, and IVA gastric and gastroesophageal junction (GEJ) cancer and showed that Imfinzi achieved a 29% improvement in event-free survival (EFS) and 22% better overall survival (OS) compared to FLOT alone.

The result has given AZ an edge with Imfinzi over MSD's PD-1 inhibitor Keytruda (pembrolizumab), which failed to show an improvement in EFS in the KEYNOTE-585 trial, which looked at peri-operative use of the drug as an addition to chemo in a similar gastric/GEJ cancer patient population.

Moving Imfinzi up the treatment pathway in this way could also have a knock-on effect for the use of Keytruda and other PD-(L)1 inhibitors approved for first-line use in advanced gastric/GEJ cancer, such as Bristol Myers Squibb's Opdivo (nivolumab) and BeOne's Tevimbra (tislelizumab).

One question facing oncologists is whether these first-line drugs will retain efficacy in patients already treated with Imfinzi at an earlier stage of their treatment journey. Approximately one-third of patients will still experience disease recurrence despite perioperative immunotherapy.

"Despite curative-intent surgery and chemotherapy, patients with resectable gastric and gastroesophageal cancers still face high recurrence rates and an urgent need for improved long-term survival," said MATTERHORN principal investigator Josep Tabernero, of the Vall d'Hebron Institute of Oncology in Barcelona, Spain.

"In MATTERHORN, nearly 70% of patients were still alive three years after treatment with the durvalumab-based perioperative regimen," he added. "This EU approval brings patients the first immunotherapy regimen to extend survival in this early setting and is poised to become the new standard of care."

AZ said in its fourth-quarter results that the MATTERHORN data was also helping to drive "encouraging uptake" of Imfinzi, which grew 28% to top $6 billion in sales for the first time in 2025.

The company is also hoping for approval in bladder cancer based on the POTOMAC results, along with readouts for several Imfinzi combinations in bladder, liver, and lung cancers.

Photo by julien Tromeur on Unsplash