Neoadjuvant Pembrolizumab in Stages I–III Deficient Mismatch Repair Colon Cancer
Ismail Gögenür, Tobias Freyberg Justesen, Line Schmidt Tarpgaard, Mustafa Bulut, Torben Frøstrup Hansen, Lars Henrik Jensen, Hans B. Rahr, Tove Kirkegaard, Lukas Balsevicius, Hans Raskov, Peter Clausager Petersen, Jens Eriksen, Søren Salomon, Anne‐Marie Kanstrup Fiehn, Søren Brandsborg, Kåre Andersson Gotschalck, Katrine J. Emmertsen, Pernille Wolder Born, Ole Thorlacius‐Ussing, Michael Bødker Lauritzen, Rene K Olesen, Laurids Østergaard Poulsen, Jakob Lykke, Jakob Hagen Vasehus Schou, Laura Buskov, Peter‐Martin Krarup, Claus L. Andersen, Per Pfeiffer, Camilla Qvortrup
Abstract
OBJECTIVE: To investigate the safety and efficacy of single-cycle pembrolizumab in patients with localized deficient mismatch repair (dMMR) colon cancer. BACKGROUND: Neoadjuvant immunotherapy has induced remarkable rates of pathologic complete response (pCR) in patients with dMMR colon cancer. However, the optimal length and type of treatment are yet to be determined. METHODS: This was an investigator-initiated, multicenter, single-arm, phase II study (ClinicalTrials.gov: NCT05662527) investigating the safety and efficacy of neoadjuvant pembrolizumab in patients with stage I-III dMMR colon cancer. Patients received a single cycle of pembrolizumab 4 mg/kg (maximum 400 mg) and underwent surgery 3 to 5 weeks later. An interim safety and efficacy analysis after including 42 patients was pre-planned. The primary outcomes were safety and efficacy (pCR in more than 20% of patients). RESULTS: Between February 2023 and September 2023, 42 patients were enrolled at 5 Danish hospitals. All patients received pembrolizumab and underwent surgery, except one patient who refused to undergo surgery. Surgery was performed a median of 32 days after pembrolizumab treatment. Twenty surgical complications were observed in 16 of 41 patients (39%), 3 of which were above Clavien-Dindo grade 2. Two were grade 3b, and 1 was a surgery-related grade 5 gastric ulcer perforation. Three adverse events were grade 3. No grade 4 or 5 adverse events were reported. Of the evaluable patients, 46% (19/41) achieved a pCR, whereas 61% had a major pathologic response. CONCLUSIONS: Neoadjuvant single-cycle pembrolizumab was well tolerated and effective in patients with localized dMMR colon cancer. Thus, the inclusion of patients was continued until 85 patients.