In a Danish phase II trial (RESET-C) reported in the Journal of Clinical Oncology, Gögenur et al found that a single cycle of neoadjuvant pembrolizumab was associated with pathologic complete response (pCR) in almost half of patients with stage I to III mismatch repair–deficient (dMMR) colon cancer.
Study Details
In the multicenter study, 84 evaluable patients enrolled between February 2023 and March 2024 received a single cycle of neoadjuvant pembrolizumab (4 mg/kg, maximum 400 mg, every-6-weeks regimen) followed by preoperative endoscopy with biopsies and surgery 3 to 5 weeks later. Patients had a median age of 74 years. The primary endpoint was pCR.
Key Findings
Among 84 patients, pCR was achieved in 37 (44%, 95% confidence interval [CI] = 33%–55%). Major pathologic response was achieved in 48 (57%, 95% CI = 46%–68%). At a median follow-up of 18.4 months (interquartile range = 16.3–21.1 months), one patient had disease recurrence, resulting in overall and disease-free survival rates of 98% and 96%, respectively.
Among 81 evaluable patients, the sensitivity, specificity, and accuracy of biopsies for predicting pCR were 68%, 75%, and 72%, respectively. In 76 evaluable patients, the sensitivity, specificity, and accuracy of endoscopic images for predicting pCR were 77%, 93%, and 86%, respectively.
No grade 4 or 5 adverse events were reported. Grade 3 adverse events were considered related to treatment in three patients, consisting of hepatitis, colitis, and asymptomatic alanine aminotransferase increase. Two patients died of surgical complications within 30 days of surgery.
The investigators concluded: “A single cycle of neoadjuvant pembrolizumab led to pCR in nearly half of patients undergoing surgery for localized dMMR colon cancer. The utility of endoscopic evaluation may inform future strategies for patient selection in nonoperative management pathways.”
Ismail Gögenur, MD, DMSc, of the Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The investigators did not report external funding for the trial. For full disclosures of the study authors, visit ascopubs.org.
