Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer

Takayuki Yoshino; Thierry Andre; Tae Won Kim; Wei Peng Yong; Kai Keen Shiu; Benny Vittrup Jensen; Lars Henrik Jensen; Cornelis J.A. Punt; Denis Smith; Rocio Garcia-Carbonero; Julia Alcaide-Garcia; Peter Gibbs; Christelle de la Fouchardiere; Fernando Rivera; Elena Elez; Dung T. Le; Noriaki Adachi; David Fogelman; Patricia Marinello; Luis A. Diaz

doi:10.1111/cas.15650

Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer

Takayuki Yoshino^*, Thierry Andre, Tae Won Kim, Wei Peng Yong, Kai Keen Shiu, Benny Vittrup Jensen, Lars Henrik Jensen, Cornelis J.A. Punt, Denis Smith, Rocio Garcia-Carbonero, Julia Alcaide-Garcia, Peter Gibbs, Christelle de la Fouchardiere, Fernando Rivera, Elena Elez, Dung T. Le, Noriaki Adachi, David Fogelman, Patricia Marinello, Luis A. Diaz

^*Corresponding author for this work

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Abstract

The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE-177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment-related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune-mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.

Original language	English
Pages (from-to)	1026-1036
Number of pages	11
Journal	CANCER SCIENCE
Volume	114
Issue number	3
DOIs	https://doi.org/10.1111/cas.15650
Publication status	Published - Mar 2023

Keywords

Asia
colorectal cancer
microsatellite instability
mismatch-repair deficiency
pembrolizumab

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10.1111/cas.15650Licence: CC BY-NC-ND

Cancer Science - 2022 - Yoshino - Pembrolizumab in Asian patients with microsatellite‐instability‐highFinal published version, 414 KBLicence: CC BY-NC-ND

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Yoshino, T., Andre, T., Kim, T. W., Yong, W. P., Shiu, K. K., Jensen, B. V., Jensen, L. H., Punt, C. J. A., Smith, D., Garcia-Carbonero, R., Alcaide-Garcia, J., Gibbs, P., de la Fouchardiere, C., Rivera, F., Elez, E., Le, D. T., Adachi, N., Fogelman, D., Marinello, P., & Diaz, L. A. (2023). Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer. CANCER SCIENCE, 114(3), 1026-1036. https://doi.org/10.1111/cas.15650

@article{c37d57ecc1f34866bdf202cfc494d262,

title = "Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer",

abstract = "The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE-177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment-related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune-mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.",

keywords = "Asia, colorectal cancer, microsatellite instability, mismatch-repair deficiency, pembrolizumab",

author = "Takayuki Yoshino and Thierry Andre and Kim, {Tae Won} and Yong, {Wei Peng} and Shiu, {Kai Keen} and Jensen, {Benny Vittrup} and Jensen, {Lars Henrik} and Punt, {Cornelis J.A.} and Denis Smith and Rocio Garcia-Carbonero and Julia Alcaide-Garcia and Peter Gibbs and {de la Fouchardiere}, Christelle and Fernando Rivera and Elena Elez and Le, {Dung T.} and Noriaki Adachi and David Fogelman and Patricia Marinello and Diaz, {Luis A.}",

note = "Publisher Copyright: {\textcopyright} 2022 Merck Sharp & Dohme LLC and The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",

year = "2023",

month = mar,

doi = "10.1111/cas.15650",

language = "English",

volume = "114",

pages = "1026--1036",

number = "3",

}

Yoshino, T, Andre, T, Kim, TW, Yong, WP, Shiu, KK, Jensen, BV, Jensen, LH, Punt, CJA, Smith, D, Garcia-Carbonero, R, Alcaide-Garcia, J, Gibbs, P, de la Fouchardiere, C, Rivera, F, Elez, E, Le, DT, Adachi, N, Fogelman, D, Marinello, P & Diaz, LA 2023, 'Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer', CANCER SCIENCE, vol. 114, no. 3, pp. 1026-1036. https://doi.org/10.1111/cas.15650

TY - JOUR

T1 - Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer

AU - Yoshino, Takayuki

AU - Andre, Thierry

AU - Kim, Tae Won

AU - Yong, Wei Peng

AU - Shiu, Kai Keen

AU - Jensen, Benny Vittrup

AU - Jensen, Lars Henrik

AU - Punt, Cornelis J.A.

AU - Smith, Denis

AU - Garcia-Carbonero, Rocio

AU - Alcaide-Garcia, Julia

AU - Gibbs, Peter

AU - de la Fouchardiere, Christelle

AU - Rivera, Fernando

AU - Elez, Elena

AU - Le, Dung T.

AU - Adachi, Noriaki

AU - Fogelman, David

AU - Marinello, Patricia

AU - Diaz, Luis A.

PY - 2023/3

Y1 - 2023/3

N2 - The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE-177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment-related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune-mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.

AB - The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE-177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment-related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune-mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.

KW - Asia

KW - colorectal cancer

KW - microsatellite instability

KW - mismatch-repair deficiency

KW - pembrolizumab

UR - http://www.scopus.com/inward/record.url?scp=85144036651&partnerID=8YFLogxK

U2 - 10.1111/cas.15650

DO - 10.1111/cas.15650

M3 - Article

C2 - 36369901

AN - SCOPUS:85144036651

SN - 1347-9032

VL - 114

SP - 1026

EP - 1036

JO - CANCER SCIENCE

JF - CANCER SCIENCE

IS - 3

ER -

Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer

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