Neoadjuvant Single-Cycle Pembrolizumab for Stage I-III MMR-Deficient Colon Cancer: The RESET-C Trial
Abstract
PURPOSE Neoadjuvant immune checkpoint inhibition has shown promise in localized deficient mismatch repair (dMMR) colorectal cancer, yet the optimal treatment duration, regimen, and methods for response evaluation remain undefined. This trial aimed to investigate the efficacy and safety of neoadjuvant pembrolizumab for patients with localized dMMR colon cancer. METHODS Participants received a single cycle of pembrolizumab (4 mg/kg, max 400 mg, every-6-weeks dosing regimen), followed by a preoperative endoscopy with biopsies and surgery 3-5 weeks later. The primary end point was pathologic complete response (pCR); secondary and exploratory end points included major pathologic response (MPR), safety, survival, and endoscopic response assessment. RESULTS From February 2023 to March 2024, 85 patients (median age 74 years) were enrolled. All received pembrolizumab; one patient declined surgery. Among 84 patients, pCR was achieved in 44% (37 of 84; 95% CI, 33 to 55), and MPR in 57% (48 of 84; 95% CI, 46 to 68). Two (2%) patients died of complications within 30 days of surgery. At a median follow-up of 18.4 months (IQR, 16.3-21.1), one patient had a recurrence, resulting in overall and disease-free survival rates of 98% and 96%. Grade 3 adverse events occurred in 11% of patients (9 of 85; 95% CI, 3 to 16), with three treatment-related events. In 81 patients, the sensitivity, specificity, and accuracy of the biopsies for predicting pCR were 68%, 75%, and 72%, respectively. In 76 patients, the sensitivity, specificity, and accuracy of the endoscopic images for predicting pCR were 77%, 93%, and 86%, respectively. CONCLUSION 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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (35)
Ismail Gögenur
Center for Surgical Science, Zealand University Hospital, Køge, Denmark
Tobias F. Justesen
Center for Surgical Science, Zealand University Hospital, Køge, Denmark
Line S. Tarpgaard
Department of Oncology, Odense University Hospital, Odense, Denmark
Mustafa Bulut
Torben F. Hansen
Lars H. Jensen
Department of Oncology, Vejle Hospital, Vejle, Denmark
Hans B. Rahr
Department of Surgery, Colorectal Cancer Center South at Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
Mikail Gögenur
Center for Surgical Science, Zealand University Hospital, Køge, Denmark
Tove Kirkegaard
Center for Surgical Science, Zealand University Hospital, Køge, Denmark
Lukas Balsevicius
Center for Surgical Science, Zealand University Hospital, Køge, Denmark
Michael Chieng
Center for Surgical Science, Zealand University Hospital, Køge, Denmark
Hans Raskov
Center for Surgical Science, Zealand University Hospital, Køge, Denmark
Mia K.S. Sørensen
Center for Surgical Science, Zealand University Hospital, Køge, Denmark
Peter C. Petersen
Department of Oncology, Zealand University Hospital, Roskilde, Denmark
Jens R. Eriksen
Department of Surgery, Zealand University Hospital, Køge, Denmark
Søren Salomon
Department of Surgery, Odense University Hospital, Odense, Denmark
Anne-Marie K. Fiehn
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Maria Dalgaard Mikkelsen
Department of Pathology, Zealand University Hospital, Roskilde, Denmark
Søren Brandsborg
Department of Surgery, Horsens Regional Hospital, Horsens, Denmark
Kåre A. Gotschalck
Department of Surgery, Horsens Regional Hospital, Horsens, Denmark
Katrine J. Emmertsen
Department of Surgery, Randers Regional Hospital, Randers, Denmark
Anne Ramlov
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
Pernille W. Born
Department of Surgery, Hvidovre Hospital, Hvidovre, Denmark
Ole Thorlacius-Ussing
Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark
Michael B. Lauritzen
Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark
René K. Olesen
Department of Oncology, Aalborg University Hospital, Aalborg, Denmark
Laurids Ø. Poulsen
Department of Oncology, Aalborg University Hospital, Aalborg, Denmark
Jakob Lykke
Department of Surgery, Herlev and Gentofte University Hospital, Herlev, Denmark
Jakob Schou
Department of Oncology, Herlev and Gentofte University Hospital, Herlev, Denmark
Laura Buskov
Department of Radiology, Bispebjerg Hospital, Bispebjerg, Denmark
Peter-Martin Krarup
Claus L. Andersen
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Niels Pallisgaard
Department of Pathology, Zealand University Hospital, Roskilde, Denmark
Per Pfeiffer
Department of Oncology, Odense University Hospital, Odense, Denmark
Camilla Qvortrup
Department of Oncology, Rigshospitalet, Copenhagen, Denmark