Researchers have presented groundbreaking findings in the treatment of deficient DNA mismatch repair (dMMR) colon cancer. Neoadjuvant pembrolizumab, commonly known as Keytruda, has shown significant efficacy in a single-cycle treatment regimen, according to results from the phase 2 RESET-C trial (NCT05662527) presented at the 2025 ASCO Gastrointestinal Cancer Symposium.

Key Findings

The clinical trial achieved a pathological complete response (pCR) rate of 44% (95% CI, 33%-55%) and a major pathological response (mPR) rate of 57% (95% CI, 46%-68%) among patients with dMMR colon cancer.

Specifically, among stage I or II patients, the pCR rate was 61%, and for stage III, it was 33%. These outcomes highlight the potential of pembrolizumab in treating various stages of dMMR colon cancer.

Future Directions

Dr. Camilla Qvortrup, a clinical associate professor from Rigshospitalet – Center for Cancer and Organ Disease in Denmark, expressed the team’s next steps. “Our goal is to integrate endoscopic evaluations, re-biopsies, and circulating tumor DNA (ctDNA) to develop a reliable response assessment tool,” Dr. Qvortrup stated. This strategy aims to pave the way for potential organ preservation techniques in cancer treatment.

Trial Details

A total of 85 patients were enrolled and treated with pembrolizumab. All participants underwent safety analysis, and 84 patients proceeded to surgery for efficacy analysis.

The demographic breakdown included a median patient age of 74 years, with 65% older than 70. Female patients made up the majority (72%), and 61% had an ECOG performance status of 0. Tumor stages were predominantly T3 (48%), T2 (25%), and T4 or T4a (15%), with node stage observations at N0 (40%), N1 (33%), and N2 (27%).

Tumor locations were also distributed with 65% in the right colon, 22% in the transverse colon, and 13% in the left colon.

Eligibility and Objectives

To be eligible for the study, patients needed to have dMMR stage I to III colon cancer with no contraindications for immunotherapy. The primary objective was the pCR rate, while secondary endpoints included safety, surgical complications, mPR, and overall survival.

Study Insights

The study aimed to address several key questions in dMMR colorectal cancer treatment. Previous investigations with neoadjuvant immune checkpoint inhibitors demonstrated positive outcomes, but optimal treatment duration and response evaluation remained unclear.

“The use of a PD-1 inhibitor for a single-cycle therapy is expected to mitigate toxicity and reduce costs,” Dr. Qvortrup noted. The trial’s findings provide valuable insights into the treatment of dMMR colon cancer.

Conclusion

The RESET-C trial marks a significant milestone in the treatment of dMMR colon cancer, showcasing the potential of pembrolizumab as a promising neoadjuvant therapy. Future developments, including the integration of endoscopic evaluations and ctDNA analysis, hold the promise of further advancing organ preservation techniques in cancer treatment.

As research progresses, these findings could revolutionize the approach to treating patients with dMMR colon cancer, offering a potentially safer and more effective treatment option.

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