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Response of Early-Stage Colon Cancer to Neoadjuvant Immunotherapy

By: Julia Fiederlein
Posted: Thursday, July 16, 2020

According to the findings of the phase II NICHE trial published in Nature Medicine, patients with early-stage mismatch repair–deficient (dMMR) and mismatch repair–proficient (pMMR) colorectal tumors may achieve partial or full remission with neoadjuvant immunotherapy. Myriam Chalabi, MD, of the Netherlands Cancer Institute, Amsterdam, and colleagues suggest that T-cell infiltration may serve as a biomarker to differentiate between responders and nonresponders in those with pMMR cancers.

“If [the new biomarker] proves to be predictive in follow-up studies, it could provide a simple way of identifying patients with microsatellite-stable tumors who could benefit from immunotherapy,” Dr. Chalabi remarked in a Netherlands Cancer Institute press release.

A total of 20 patients with dMMR tumors and 15 patients with pMMR tumors completed the study. Both groups received ipilimumab/nivolumab for approximately 4 weeks prior to having surgery at about 6 weeks after enrollment. Additionally, seven patients from the pMMR group were randomly assigned to be treated with celecoxib. Tissue samples, obtained prior to and during the surgical procedures, were evaluated for T-cell infiltration and histopathologic response.

The percentages of patients with dMMR and pMMR tumors who experienced pathologic responses were 100% and 27%, respectively. Of the 20 responders who had dMMR tumors, 19 experienced modified partial remission of up to 10% viable tumor remaining after surgery. This included 12 patients who experienced a pathologic complete response. Of the four responders who had pMMR tumors, three achieved modified partial remission. One responder had 1% of their viable tumor remaining. Of the patients with pMMR tumors who received celecoxib , one patient achieved modified partial remission, one patient achieved partial remission, and two experienced a 10% to 50% tumor regression.

Notably, the investigators determined that CD8-positive PD-1 T-cell infiltration may be a driver of response in patients with pMMR tumors. “[A] longer duration of treatment may potentially further increase response rates in [patients with] pMMR tumors,” the investigators proposed.

Disclosure: For full disclosures of the study authors, visit nature.com.



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