Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial

Ismail Gögenur; Tobias Freyberg Justesen; Line Schmidt Tarpgaard; Mustafa Bulut; Hans Bjarke Rahr; Tove Kirkegaard; Lukas Balsevicius; Hans Raskov; Søren Salomon; Anne-Marie Kanstrup Fiehn; Søren Brandsborg; Kåre Andersson Gotschalck; Katrine J Emmertsen; Pernille Wolder Born; Ole Thorlacius-Ussing; Michael Bødker Lauritzen; René Krøjgaard Olesen; Laurids Østergaard Poulsen; Jakob Lykke; Jakob Schou; Laura Buskov; Peter-Martin Krarup; Claus Lindbjerg Andersen; Per Pfeiffer; Camilla Qvortrup

doi:10.1097/SLA.0000000000006611

Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial

Ismail Gögenur, Tobias Freyberg Justesen, Line Schmidt Tarpgaard, Mustafa Bulut, Hans Bjarke Rahr, Tove Kirkegaard, Lukas Balsevicius, Hans Raskov, Søren Salomon, Anne-Marie Kanstrup Fiehn, Søren Brandsborg, Kåre Andersson Gotschalck, Katrine J Emmertsen, Pernille Wolder Born, Ole Thorlacius-Ussing, Michael Bødker Lauritzen, René Krøjgaard Olesen, Laurids Østergaard Poulsen, Jakob Lykke, Jakob SchouLaura Buskov, Peter-Martin Krarup, Claus Lindbjerg Andersen, Per Pfeiffer, Camilla Qvortrup

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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.

Original language	English
Article number	10.1097/SLA.0000000000006611
Journal	Annals of Surgery
ISSN	0003-4932
DOIs	https://doi.org/10.1097/SLA.0000000000006611
Publication status	E-pub / Early view - 18 Dec 2024

Keywords

colon cancer
deficient mismatch repair system
immune checkpoint inhibitor

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10.1097/SLA.0000000000006611

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Gögenur, I., Justesen, T. F., Tarpgaard, L. S., Bulut, M., Rahr, H. B., Kirkegaard, T., Balsevicius, L., Raskov, H., Salomon, S., Fiehn, A.-M. K., Brandsborg, S., Gotschalck, K. A., Emmertsen, K. J., Born, P. W., Thorlacius-Ussing, O., Lauritzen, M. B., Olesen, R. K., Poulsen, L. Ø., Lykke, J., ... Qvortrup, C. (2024). Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial. Annals of Surgery, Article 10.1097/SLA.0000000000006611. Advance online publication. https://doi.org/10.1097/SLA.0000000000006611

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title = "Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial",

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.",

keywords = "colon cancer, deficient mismatch repair system, immune checkpoint inhibitor",

author = "Ismail G{\"o}genur and Justesen, {Tobias Freyberg} and Tarpgaard, {Line Schmidt} and Mustafa Bulut and Rahr, {Hans Bjarke} and Tove Kirkegaard and Lukas Balsevicius and Hans Raskov and S{\o}ren Salomon and Fiehn, {Anne-Marie Kanstrup} and S{\o}ren Brandsborg and Gotschalck, {K{\aa}re Andersson} and Emmertsen, {Katrine J} and Born, {Pernille Wolder} and Ole Thorlacius-Ussing and Lauritzen, {Michael B{\o}dker} and Olesen, {Ren{\'e} Kr{\o}jgaard} and Poulsen, {Laurids {\O}stergaard} and Jakob Lykke and Jakob Schou and Laura Buskov and Peter-Martin Krarup and Andersen, {Claus Lindbjerg} and Per Pfeiffer and Camilla Qvortrup",

year = "2024",

month = dec,

day = "18",

doi = "10.1097/SLA.0000000000006611",

language = "English",

journal = "Annals of Surgery",

issn = "0003-4932",

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Gögenur, I, Justesen, TF, Tarpgaard, LS, Bulut, M, Rahr, HB, Kirkegaard, T, Balsevicius, L, Raskov, H, Salomon, S, Fiehn, A-MK, Brandsborg, S , Gotschalck, KA , Emmertsen, KJ, Born, PW, Thorlacius-Ussing, O, Lauritzen, MB, Olesen, RK, Poulsen, LØ, Lykke, J, Schou, J, Buskov, L, Krarup, P-M, Andersen, CL, Pfeiffer, P & Qvortrup, C 2024, 'Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial', Annals of Surgery. https://doi.org/10.1097/SLA.0000000000006611

TY - JOUR

T1 - Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer

T2 - A Clinical Trial

AU - Gögenur, Ismail

AU - Justesen, Tobias Freyberg

AU - Tarpgaard, Line Schmidt

AU - Bulut, Mustafa

AU - Rahr, Hans Bjarke

AU - Kirkegaard, Tove

AU - Balsevicius, Lukas

AU - Raskov, Hans

AU - Salomon, Søren

AU - Fiehn, Anne-Marie Kanstrup

AU - Brandsborg, Søren

AU - Gotschalck, Kåre Andersson

AU - Emmertsen, Katrine J

AU - Born, Pernille Wolder

AU - Thorlacius-Ussing, Ole

AU - Lauritzen, Michael Bødker

AU - Olesen, René Krøjgaard

AU - Poulsen, Laurids Østergaard

AU - Lykke, Jakob

AU - Schou, Jakob

AU - Buskov, Laura

AU - Krarup, Peter-Martin

AU - Andersen, Claus Lindbjerg

AU - Pfeiffer, Per

AU - Qvortrup, Camilla

PY - 2024/12/18

Y1 - 2024/12/18

N2 - 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.

AB - 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.

KW - colon cancer

KW - deficient mismatch repair system

KW - immune checkpoint inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85212944416&partnerID=8YFLogxK

U2 - 10.1097/SLA.0000000000006611

DO - 10.1097/SLA.0000000000006611

M3 - Journal article

C2 - 39692004

SN - 0003-4932

JO - Annals of Surgery

JF - Annals of Surgery

M1 - 10.1097/SLA.0000000000006611

ER -

Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial

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Keywords

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