Neoadjuvant Single-Cycle Pembrolizumab for Stage I-III MMR-Deficient Colon Cancer: The RESET-C Trial.

Area of Science:

• Oncology
• Gastroenterology
• Immunotherapy

Background:

• Neoadjuvant immune checkpoint inhibition shows potential for localized deficient mismatch repair (dMMR) colorectal cancer.
• Optimal treatment duration, regimen, and response evaluation methods for this approach are not yet established.

Purpose of the Study:

• To investigate the efficacy and safety of neoadjuvant pembrolizumab in patients with localized dMMR colon cancer.
• To evaluate treatment response using pathologic complete response (pCR) and other metrics.

Main Methods:

• Eighty-five patients with localized dMMR colon cancer received one cycle of pembrolizumab.
• Treatment was followed by preoperative endoscopy, biopsies, and surgery within 3-5 weeks.
• Primary endpoint was pCR; secondary endpoints included major pathologic response (MPR), safety, survival, and endoscopic assessment.

Main Results:

• Pathologic complete response (pCR) was achieved in 44% of patients, with a major pathologic response (MPR) in 57%.
• Overall and disease-free survival rates were high (98% and 96%) at median follow-up of 18.4 months.
• Endoscopic evaluation demonstrated high sensitivity (77%) and specificity (93%) for predicting pCR.

Conclusions:

• A single cycle of neoadjuvant pembrolizumab is effective in a significant proportion of patients with localized dMMR colon cancer.
• Endoscopic evaluation may be valuable for future nonoperative management strategies in this patient population.