July 10, 2024

Clinical trial for rectal cancer subtype shows promise for less aggressive treatment

The findings were so promising that the clinical trial is being redesigned to investigate whether radiation treatment can also be avoided.

Data from a clinical trial show that a dual immunotherapy regimen plus short course radiation for the treatment of rectal cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) can be effective enough to avoid chemotherapy and colostomy-requiring surgery.

The data from the EA2201 study were so promising that the clinical trial is being redesigned to investigate whether radiation treatment can also be avoided. Most patients in the study — 57% — had a complete clinical response according to scan results, or a complete surgical response. Of those who had rectal surgery, which was the standard of care when the clinical trial began, 100% had no cancer cells left, according to pathology reports. The study participants, who either had stage 2 or stage 3 MSI-H/dMMR rectal cancer, were treated with nivolumab plus ipilimumab before and after receiving short course radiation therapy.

Kristen Ciombor, MD, MSCI

Kristen Ciombor, MD, MSCI, Ingram Associate Professor of Cancer Research and co-leader of the Translational Research and Interventional Oncology Research Program at Vanderbilt-Ingram Cancer Center, presented the data Friday in Munich, Germany, at the European Society for Medical Oncology Gastrointestinal Cancers Congress 2024.

She is the principal investigator of the EA2201 study, which is sponsored by the National Cancer Institute and being administered through the ECOG-ACRIN Cancer Research Group. Around 5% of rectal cancer patients have MSI-H tumors, characterized by a higher number of repeated DNA base sequences. These tumors usually contain many more mutations than non-MSI-H tumors. Microsatellite instability can be found in both sporadic and hereditary forms of colorectal cancer; the hereditary form, termed Lynch syndrome, can be found in young patients in particular.

The data were for the first 14 patients enrolled in the study. The aim of the study, which began recruiting participants nationally in May 2021, was to check whether a dual immunotherapy regimen plus short course radiation could be an alternative to the standard of treatment, which at that time called for chemotherapy, more aggressive chemoradiation therapy and surgical resection.

“What we found was that of the three people who wound up going to surgery, none had any cancer left at the time of surgery,” Ciombor said. “Additionally, five patients had disappearance of their cancer on scans and didn’t need surgery. So overall, 57 percent of patients had a complete disappearance of their cancer on scans or at surgery. This looks very promising in terms of avoiding chemotherapy, long-course radiation and possibly surgery, which is the way that patients with rectal cancer currently get treated.”

The patients were fully involved in deciding whether to undergo surgery.

“When we designed this study, we weren’t certain we would be able to avoid surgery, so we wrote into the protocol that everybody would get surgery,” Ciombor said. “One of the patients who had surgery had a complete response on scan but still decided to have surgery because at the time that was the standard of care. Two others went on to surgery because on scans we saw what we thought was residual tumor, but it turned out it was scar tissue that was showing up on the imaging and there was no tumor left. Additionally, some patients saw their tumors disappear on scans and decided not to pursue surgery. Those patients basically had tumor disappearance on their imaging, and none of the patients have had disease recurrence.”

The EA2201 clinical study is temporarily closed to accrual because it is being redesigned due to the positive results.

“We haven’t answered yet if we can avoid radiation,” Ciombor said. “That’s the next step. What we have shown is that none of these patients needed chemotherapy. In a large proportion of patients, we can probably avoid surgery too. Overall, this is a very exciting advance in the treatment of patients with MSI-H rectal cancer, and hopefully, in the near future, we can figure out a way to extend these results to patients with microsatellite stable (MSS) rectal cancer as well.”

The study received support from the National Cancer Institute (U10CA180794), (U10CA180821), (U10CA180820), (U10CA180868), (U10CA180888), (UG1CA189956), and (UG1CA233270). The study was also supported by the Adventure Alle Family Fund.