Durvalumab and FLOT show promise for gastroesophageal cancer

How New Cancer Therapies Are Forging a New Standard for Gastroesophageal Cancer

A new treatment approach for gastroesophageal cancer, combining the drugs durvalumab and FLOT, is showing promise but also presenting significant logistical challenges for community oncology centers, according to detailed reporting from CancerNetwork.

At the heart of this approach is the use of a neoadjuvant regimen consisting of durvalumab, an immunotherapy, and the chemotherapy combination FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) for patients with T2N0 disease, which is technically classified as stage I. This choice is driven by a critical clinical reality: our diagnostic tools are imperfect. Literature shows that for patients initially diagnosed with clinical T2N0 disease, upward of 60% are found to have a more advanced stage of cancer—a process called pathological upstaging—at the time of surgery.

If a patient undergoes surgery first and is then found to have upstaged disease, they face a difficult road. They must then receive adjuvant therapy after a major operation like an esophagectomy or a gastrectomy. These post-surgical therapies are notoriously difficult for patients to tolerate. By contrast, the aggressive FLOT plus durvalumab regimen is much better tolerated before surgery, which is why many oncologists are now leaning toward a neoadjuvant approach to spare patients this future hardship.

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The Logistical Tightrope: Managing Long Infusion Times

Implementing this new standard of care is no simple task. The FLOT regimen is long, and adding durvalumab extends chair time even further. This creates a significant operational hurdle for community centers, which often face constraints on infusion chair availability and scheduling.

One of the most common reasons for a delay in chemotherapy is low blood counts, specifically neutropenia or severe thrombocytopenia. To prevent this, a practical strategy is to have patients receive G-CSF (granulocyte colony-stimulating factor) with every infusion. This helps ensure their blood counts remain at a level that allows them to receive the next treatment cycle on schedule. A missed appointment due to low counts isn’t just a delay; it’s wasted chair space and lost time in a patient’s critical treatment window.

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Another challenge comes from other complex treatment regimens, such as zolbetuximab plus chemotherapy (FOLFOX). For the first one to two doses, zolbetuximab must be administered very slowly to prevent severe nausea and vomiting. This often means splitting the treatment over two days: zolbetuximab on day one and FOLFOX on day two. However, once patients tolerate the initial doses, the two-day treatment can usually be consolidated into a single day, improving both patient experience and clinic efficiency. The hope for the future, many practitioners say, lies in subcutaneous options that could dramatically shorten infusion times compared to traditional IV delivery.

Biomarker Testing: The Future of Personalized Treatment

The modern management of gastroesophageal cancer is increasingly defined by biomarker testing. Experts emphasize that four biomarkers are now essential for guiding treatment decisions: claudin 18.2, HER2, PD-L1, and mismatch repair/MSI-high status. Each of these biomarkers has an immediate and direct impact on the treatment options available to a patient.

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The operational advice for clinics is to send for broad next-generation sequencing (NGS) panels at any stage of the disease. This approach provides a comprehensive report, not just for the four key biomarkers but also for rarer alterations like RET fusions, NTRK alterations, and BRAF V600E mutations. Having all this information on a single document is far more efficient than testing piecemeal, where results can get scattered across a patient’s chart and easily missed.

“This is one of my favorite topics. Biomarker testing in gastroesophageal cancer is rapidly developing, and there are 4 biomarkers that you must have: claudin 18.2, HER2, PD-L1, and mismatch repair/MSI-high testing, because those have immediate relevance to patients in terms of their treatment options.”

Novel Mechanisms to Overcome Treatment Resistance

The claudin 18.2 space is a prime example. While a monoclonal antibody targeting this biomarker is already approved, the field is progressing rapidly with new mechanisms. These include antibody-drug conjugates (ADCs), bispecific antibodies designed to help the immune system better target the cancer, and more sophisticated cellular therapies like CAR T-cell therapy and tumor-infiltrating lymphocytes (TILs).