Optimizing Neoadjuvant Therapy Efficacy in dMMR Gastroesophageal Cancer


Tailoring neoadjuvant therapy regimens for patients with mismatch repair deficient gastroesophageal cancer represents a future step in terms of research.

Regarding patients with mismatch repair deficient (dMMR) gastroesophageal cancer, the next step in research may involve optimizing efficacy outcomes with single-agent neoadjuvant immunotherapy while avoiding the toxicity associated with combination therapies, according to Adrienne Bruce Shannon, MD.

In a conversation with CancerNetwork®, Shannon, a complex general surgical oncology fellow at Moffitt Cancer Center, discussed how she plans to build upon findings from a study she presented at the Society of Surgical Oncology (SSO) 2024 Annual Meeting.Findings from her presentation highlighted that select patients with dMMR gastroesophageal cancer achieved responses to neoadjuvant immune checkpoint inhibitors.

Shannon highlighted other research in the space including the phase 2 NEONIPIGA study (NCT04006262) evaluating nivolumab (Opdivo) plus ipilimumab (Yervoy) among those with dMMR localized gastroesophageal cancer. She said that tailoring treatment regimens for this population may involve determining an optimal number of treatment cycles as well as the feasibility of administering monotherapy instead of combination treatment.


In terms of efficacy, we still don’t have a true regimen for these [patients]. NEONIPIGA is a recent trial looking at neoadjuvant nivolumab and ipilimumab in all-comers who have gastric cancer. One of the interesting things about our study is 4 of 5 of our patients—instead of receiving of nivolumab/ipilimumab, which is combination therapy as we would classify it—received single-agent therapy. We’re seeing these results with just a single agent, and there’s such an increased toxicity level with the combination therapy. The next step would be saying, "OK, can we now design a trial that only uses one of those agents to try to decrease the toxicity profile, but maybe sees the same outcomes that we’re seeing with NEONIPIGA?"

You kind of see some of that in our patient sample, but I’d like to see that done on a larger scale to try to really tailor the regimen itself. There’s also not necessarily a true established number of cycles that you do. In our institution, [patients] receive anywhere from 4 to 6 [cycles] when they receive neoadjuvant [therapy]. That’s mostly extrapolated from studies that have already been in production. Nobody said that this is the true regimen that we should be giving these patients because it’s a small sample. But that would also be the next step: to try to tailor what we are giving them. Also, can we get them down to monotherapy as opposed to combination therapy? If they potentially [have recurrence] down the road, that then opens up more options for them in terms of managing recurrence.


Shannon AB, Mehta RJ, Mok SR, et al. Pathologic response to neoadjuvant immunotherapy in DNA mismatch repair protein-deficient gastroesophageal cancers. Presented at the Society of Surgical Oncology 2024 Annual Meeting; March 20-24, 2024; Atlanta, GA. Abstract 94.

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