Abstract
Objective:
This clinical trial investigated 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 pathological complete response 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 three to five weeks later. An interim safety and efficacy analysis after including 42 patients was pre-planned. The primary outcomes were safety and efficacy (pathological complete response in more than 20% of patients).
Results:
Between February 2023 and September 2023, 42 patients were enrolled at five 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%), three of which were above Clavien-Dindo grade 2. Two were grade 3b, and one 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 pathological complete response, while 61% had a major pathological response.
Conclusion:
In conclusion, 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.
This clinical trial investigated 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 pathological complete response 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 three to five weeks later. An interim safety and efficacy analysis after including 42 patients was pre-planned. The primary outcomes were safety and efficacy (pathological complete response in more than 20% of patients).
Results:
Between February 2023 and September 2023, 42 patients were enrolled at five 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%), three of which were above Clavien-Dindo grade 2. Two were grade 3b, and one 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 pathological complete response, while 61% had a major pathological response.
Conclusion:
In conclusion, 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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Annals of Surgery |
| ISSN | 0003-4932 |
| DOI | |
| Status | Accepteret/In press - 2025 |
Bibliografisk note
Funding Information:Funding : The study was supported by the Danish Comprehensive Cancer Center (grant number 16), Dagmar Marshalls Foundation (grant number not provided), Medical Doctor Sofus Carl Emil Friis and Wife Olga Doris Friis\u2019 Foundation (grant number not provided), Danish Cancer Society (grant number R343-A19803), Axel Muusfeldt\u2019s Foundation (grant numbers 2022-0016 and 2023-0486), Frimodt Heineke Foundation (grant number not provided), Manufacturer Einar Willumsen\u2019s Memorial Fund (grant number not provided), Timber Merchant Vilhelm Bang\u2019s Fund (grant number not provided), NEYE Foundation (grant number not provided), Eva and Henry Fr\u00E6nkel\u2019s Memorial Fund (grant number not provided), Vissing Foundation (grant number 532937 AHO/LAX), Helge Peetz and Verner Peetz and wife Vilma Peetz\u2019s Scholarship (grant number not provided), and Merchant L.F. Foght\u2019s Fund (grant number 22.340). The funding parties were not involved in the design of the study, the execution of the study, the analyses, or the interpretation of the study results.
Publisher Copyright:
Copyright © 2024 The Author(s).