With deep expertise in biopharma innovation and oncology research and development, Ivan Kairatov offers a unique perspective on the latest breakthroughs in cancer treatment. Today, we delve into the recent positive opinion from European regulators for AstraZeneca’s Imfinzi in combination with chemotherapy for early-stage gastric and gastroesophageal junction cancers. Our conversation will explore the clinical significance of the MATTERHORN trial data, the complexities of the perioperative treatment approach, and the manageable safety profile of this new regimen. We will also discuss the global regulatory momentum in the context of rising diagnoses and what this signals for the broader strategy of using immunotherapy in earlier stages of cancer.
The Imfinzi-FLOT regimen demonstrated a 22% reduction in the risk of death in its trial. Could you elaborate on the clinical significance of this figure for patients with early-stage gastric cancer and explain how this new option could change the standard of care?
That 22% figure is more than just a statistic; it’s a profound shift in hope for patients diagnosed with a notoriously difficult disease. Gastric cancer is the fifth leading cause of cancer death globally, so any progress feels monumental. When you translate that percentage into survival, you see that after three years, 69% of patients on the Imfinzi regimen were still alive, compared to 62% on chemotherapy alone. For a patient and their family, that difference is everything. This isn’t an incremental improvement; it’s a meaningful leap that establishes a new, more effective standard of care. It provides a powerful tool to use when the cancer is still localized and the goal is a cure, fundamentally changing the conversation in the clinic from one of management to one of potential eradication.
This treatment is a complex, multi-stage perioperative regimen. Can you walk us through the clinical rationale for using Imfinzi both before and after surgery, and what are the key challenges in managing patient adherence throughout this extended timeline?
The rationale for this multi-stage attack is to fight the cancer on two fronts. Before surgery, in the neoadjuvant phase, the combination of Imfinzi and FLOT chemotherapy works to shrink the tumor, making the subsequent surgery cleaner and more effective. It’s about priming the battlefield for success. Then, after the tumor is removed, the adjuvant phase begins. This is crucial because even the best surgery can leave behind microscopic cancer cells. Continuing treatment with Imfinzi helps the body’s own immune system hunt down and destroy these remaining cells, which are the seeds of future recurrence. The main challenge, of course, is the sheer length and intensity of the journey. Patients are navigating the side effects of potent chemotherapy, the physical recovery from major surgery, and then continued immunotherapy. It takes an incredible amount of resilience, and the biggest hurdle is managing patient fatigue and morale to ensure they can complete the full course of this potentially curative therapy.
Considering the addition of Imfinzi to intensive FLOT chemotherapy did not increase the rate of severe adverse events, what does this safety profile mean for oncologists? Please share some practical steps for managing patient care and potential side effects with this combination therapy.
From a clinical standpoint, this is a massive relief and a game-changer. Whenever you add a new drug to an already intense regimen like FLOT, the primary concern is whether you’re pushing the patient’s body past its limit. The fact that the rate of Grade 3 or higher adverse events was consistent across both arms is incredibly reassuring. It means we can offer a more effective therapy without a significant trade-off in severe toxicity. For oncologists, this translates to a more confident treatment recommendation. Practically, management requires heightened vigilance. We need to educate patients to report any new symptoms immediately, as immune-related side effects can be subtle and differ from typical chemo reactions. It also demands a proactive, multidisciplinary approach, with close monitoring of organ function and being ready to intervene early to manage any emerging issues, ensuring the patient remains well enough to benefit from the full treatment course.
With approvals in the US and a positive opinion in the EU, how does this global regulatory momentum address the projected rise in early-stage gastric and GEJ cancer diagnoses, which is expected to affect around 62,000 new patients by 2030 in these regions?
This global alignment is critically important because it ensures that a new standard of care can be established quickly and broadly, right as the need is growing. We’re looking at a significant increase in diagnoses, with an estimated 62,000 new patients by 2030 in just the US, EU, and Japan. Having this powerful new option available across major regions means we are prepared to meet that rising challenge head-on. This synchronized regulatory progress avoids the “postcode lottery,” where a patient’s access to the best treatment depends on where they live. It accelerates the adoption of a superior therapy, allowing us to offer a greater chance of a cure to thousands more people each year as this trend of earlier diagnosis continues to grow.
This is noted as the third perioperative Imfinzi-based regimen available in the EU. What does this broader strategy of moving immunotherapy into earlier-stage cancers, like gastric cancer, signal about the future of oncology, and what specific benefits does this approach offer over traditional methods?
This absolutely signals a paradigm shift in oncology. For decades, our most powerful and innovative drugs, including immunotherapies, were reserved for late-stage, metastatic disease, often as a last resort. The strategy now is to bring these game-changing treatments to the front lines—into the early-stage, curative setting. The benefit is immense. By using immunotherapy when the tumor burden is lower and the patient’s immune system is generally stronger, we have a much greater chance of eliminating the cancer completely and preventing it from ever coming back. This is about moving from simply extending life in advanced cancer to truly curing it in its earlier stages. It’s a more hopeful, proactive approach that leverages our best science at the moment of greatest opportunity.
What is your forecast for the treatment of early-stage gastric cancer over the next decade?
I believe the next decade will be defined by personalization and de-escalation. We’ll move beyond a one-size-fits-all approach, using biomarkers to identify which patients will benefit most from aggressive perioperative chemo-immunotherapy and, just as importantly, which patients might be able to achieve the same outcome with less intensive treatment. We’ll see smarter combinations and perhaps even neoadjuvant approaches that are so effective they could, in select cases, allow for less radical surgeries or even obviate the need for surgery altogether. The goal will be to maximize the cure rate while minimizing the long-term physical and emotional burden on the patient, making survivorship not just longer, but better.
