Managing Patients With No Pathologic Response After Durvalumab Plus FLOT

In an interview with CancerNetwork®, Sunnie Kim, MD, associate professor of medicine in the Division of Medical Oncology at the University of Colorado School of Medicine, and a gastrointestinal medical oncologist at the University of Colorado Cancer Center, discussed how she approaches postoperative management for patients with gastric or gastroesophageal junction cancer who show no treatment effect on pathology after preoperative durvalumab (Imfinzi) plus FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel), the perioperative regimen supported by the phase 3 MATTERHORN trial (NCT04592913).

Kim noted that there is currently no proven alternative adjuvant strategy for these patients. She pointed to the phase 2 EORTC 1707 VESTIGE trial (NCT03443856), in which adjuvant nivolumab (Opdivo) plus ipilimumab (Yervoy) did not improve disease-free survival compared with continued chemotherapy in high-risk patients after preoperative chemotherapy and resection. As a result, Kim continues adjuvant FLOT plus durvalumab in patients without a pathologic response, noting that clinical and radiologic improvements should also be weighed. She emphasized the need for more effective strategies to overcome resistance to this regimen.

Transcript:

Kim: Unfortunately, at this time we don’t have a great alternative strategy in the adjuvant setting. There have been studies looking at whether different adjuvant therapies, like ipilimumab plus nivolumab, could work better in the era of FLOT alone, not necessarily FLOT plus durvalumab, and unfortunately we didn’t see a benefit.² For patients who don’t have any pathological response after neoadjuvant FLOT plus durvalumab, I do continue FLOT on the back end with durvalumab, because sometimes we have patients who have clinical or radiologic improvements, and that’s to be considered as well as the pathological response. Of course, in the future, we need more effective strategies and treatments that can overcome resistance to FLOT plus durvalumab. My practice right now is to still offer the same treatment after surgery.

References

1. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med. 2025;393(3):217-230. doi:10.1056/NEJMoa2503701

2. Lordick F, Mauer ME, Stocker G, et al. Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study. Ann Oncol. 2025;36(2):197-207. doi:10.1016/j.annonc.2024.10.829