Nivolumab Fails to Benefit Esophageal Cancer Treatment in EA2174 Trial: Dr Jennifer Eads

This new analysis of nivolumab presented at ASCO 2024 shows the immune checkpoint inhibitor did not convery benefit when added to a regimen of neoadjuvant carboplatin, paclitaxel, and radiation.

A new analysis of the ECOG-ACRIN EA2174 clinical trial presented today at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO 2024) showed that adding nivolumab to neoadjuvant carboplatin, paclitaxel, and radiation for esophageal and gastroesophageal junction adenocarcinoma did not improve the outcome of pathological complete response in these patients.1

Still, lead author Jennifer Eads, MD, physician lead, GI Clinical Research; director, National Clinical Trials Network, Abramson Cancer Center; and associate professor of clinical medicine (hematology-oncology), Penn Medicine, remains hopeful, with results pending for the study’s adjuvant analysis and forthcoming next-generation sequencing and ctDNA [circulating tumor DNA] analyses on patient tissue and blood samples.

Eads presented, “A phase II/III study of peri-operative nivolumab (nivo) and ipilimumab (ipi) in patients (pts) with locoregional esophageal (E) and gastroesophageal junction (GEJ) adenocarcinoma: results of the neoadjuvant pathologic complete response (pCR) rate (ECOG-ACRIN EA2174).”


Why it is important to study nivolumab plus ipilimumab in locoregional esophageal and gastroesophageal junction adenocarcinoma?

I think it was really important to perform the EA2174 trial [NCT03604991] because we know that immune checkpoint inhibitor therapy in the metastatic setting is beneficial, and for patients with localized disease, our hope is that they never get to the metastatic setting. Ideally, we want to be able to introduce to them an agent that we know is efficacious in their disease, in a treatment approach that is hopefully curative for them. I think it was definitely an important study to do, to look at whether or not the addition of immune checkpoint inhibitor therapy to chemotherapy and radiation was beneficial, because that would have allowed patients to receive this effective agent when they were going for cure of their disease.

Unfortunately, we had a negative outcome. But at least we know that now and hopefully, we can continue to move forward and find other ways to improve the treatment outcomes for the patients which, which actually the ESOPEC trial [NCT02509286] will probably do.2

What are planned next steps in your investigation, with this most recent analysis not showing a benefit with nivolumab?

So it was a negative trial, but I still think that there's a lot of things that we can learn. First of all, there is the adjuvant element of the study that is still pending. We're still waiting to find out whether or not adjuvant nivolumab vs adjuvant nivolumab and ipilimumab, if there's a disease-free survival benefit between those 2 arms.

The other thing that we did with this trial was that we have collected tissue from participants at baseline and at the time of their surgical resection, and we have also collected blood specimens throughout the course of their treatments—so at baseline, following chemoradiation, at the time of surgery, and then at a couple time points during their adjuvant course of treatment. And we are planning on performing next-generation sequencing analyses and ctDNA [circulating tumor DNA] analyses to determine if there are particular pathways that we might be able to identify that may have rendered a patient more responsive to the addition of immune checkpoint inhibitor therapy, and also to determine if circulating tumor DNA is actually a reliable biomarker for determining disease status at the molecular level.


1. Eads JR, Graham N, Gibson MK, et al. A phase II/III study of peri-operative nivolumab (nivo) and ipilimumab (ipi) in patients (pts) with locoregional esophageal (E) and gastroesophageal junction (GEJ) adenocarcinoma: results of the neoadjuvant pathologic complete response (pCR) rate (ECOG-ACRIN EA2174). Presented at: ASCO 2024; May 31-June 4, 2024; Chicago, IL. Abstract 4000.

2. Perioperative chemotherapy compared to neoadjuvant chemoradiation in patients with adenocarcinoma of the esophagus (ESOPEC). Updated May 8, 2024. Accessed June 1, 2024.

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