Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Cetuximab plus irinotecan administered biweekly with reduced infusion time to heavily pretreated patients with metastatic colorectal cancer and related RAS and BRAF mutation status

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{a8d3c35490334fc38278df8f3562dfcf,
title = "Cetuximab plus irinotecan administered biweekly with reduced infusion time to heavily pretreated patients with metastatic colorectal cancer and related RAS and BRAF mutation status",
abstract = "Metastatic colorectal cancer (mCRC) is treated with cetuximab 250 mg/m2 administered weekly over 1 hour or biweekly (q2w) over 3.5 hours when combined with irinotecan. This prospective study investigated cetuximab 500 mg/m2 plus irinotecan 180 mg/m2 administered q2w over 1.5 hours independent of RAS or BRAF mutation status in mCRC patients in a third-line setting. The intention-to-treat population included 181 patients. No patients had complete response, 18% had partial responses (PR) and 48% stable disease (SD). For cetuximab, a relative dose intensity of ≥90% was reached in 78% and for irinotecan in 67% of the patients. Grade 3 to 4 toxicities were pain (17%), fatigue (9%), neutropenia (8%), diarrhea (8%), rash (8%), infection (7%) and hypersensitivity (3%). No deaths occurred. Next-generation sequencing in 96.7% of the patients revealed that 50.3% had RAS and BRAFV600E wild type (WT), with a mutation type (MT) in 45.1% of the RAS and 4.4% of the BRAFV600E genes. In patients with RAS-WT and RAS-MT tumors, a PR was obtained in 32% and 4% (P = .000003) and an SD in 43% and 53%, respectively, with a superior PFS (6.2 vs 3.7 months; hazard ratio [HR] 2.12, P = .00001) and OS (12.9 vs 8.8 months; HR 1.71, P = .0008). Treatment efficacy was poor in 7.4% of patients with an RAS mutation outside KRAS exon 2 and in 38% of patients with KRAS exon 2 mutations. Administration of cetuximab and irinotecan q2w, shortening treatment time from 3.5 to 1.5 hours, is recommended as standard therapy.",
keywords = "cetuximab, colorectal cancer, irinotecan, RAS-mutation, biweekly",
author = "Jensen, {Benny Vittrup} and Schou, {Jakob V} and Mette Yilmaz and Johannesen, {Helle H} and Kristin Skougaard and Dorte Linnemann and Hogdall, {Estrid V} and Larsen, {Finn O} and Johansen, {Julia S} and Per Pfeiffer and Nielsen, {Dorte L}",
note = "{\textcopyright} 2020 UICC.",
year = "2021",
month = may,
day = "15",
doi = "10.1002/ijc.33448",
language = "English",
volume = "148",
pages = "2542--2556",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "JohnWiley & Sons, Inc",
number = "10",

}

RIS

TY - JOUR

T1 - Cetuximab plus irinotecan administered biweekly with reduced infusion time to heavily pretreated patients with metastatic colorectal cancer and related RAS and BRAF mutation status

AU - Jensen, Benny Vittrup

AU - Schou, Jakob V

AU - Yilmaz, Mette

AU - Johannesen, Helle H

AU - Skougaard, Kristin

AU - Linnemann, Dorte

AU - Hogdall, Estrid V

AU - Larsen, Finn O

AU - Johansen, Julia S

AU - Pfeiffer, Per

AU - Nielsen, Dorte L

N1 - © 2020 UICC.

PY - 2021/5/15

Y1 - 2021/5/15

N2 - Metastatic colorectal cancer (mCRC) is treated with cetuximab 250 mg/m2 administered weekly over 1 hour or biweekly (q2w) over 3.5 hours when combined with irinotecan. This prospective study investigated cetuximab 500 mg/m2 plus irinotecan 180 mg/m2 administered q2w over 1.5 hours independent of RAS or BRAF mutation status in mCRC patients in a third-line setting. The intention-to-treat population included 181 patients. No patients had complete response, 18% had partial responses (PR) and 48% stable disease (SD). For cetuximab, a relative dose intensity of ≥90% was reached in 78% and for irinotecan in 67% of the patients. Grade 3 to 4 toxicities were pain (17%), fatigue (9%), neutropenia (8%), diarrhea (8%), rash (8%), infection (7%) and hypersensitivity (3%). No deaths occurred. Next-generation sequencing in 96.7% of the patients revealed that 50.3% had RAS and BRAFV600E wild type (WT), with a mutation type (MT) in 45.1% of the RAS and 4.4% of the BRAFV600E genes. In patients with RAS-WT and RAS-MT tumors, a PR was obtained in 32% and 4% (P = .000003) and an SD in 43% and 53%, respectively, with a superior PFS (6.2 vs 3.7 months; hazard ratio [HR] 2.12, P = .00001) and OS (12.9 vs 8.8 months; HR 1.71, P = .0008). Treatment efficacy was poor in 7.4% of patients with an RAS mutation outside KRAS exon 2 and in 38% of patients with KRAS exon 2 mutations. Administration of cetuximab and irinotecan q2w, shortening treatment time from 3.5 to 1.5 hours, is recommended as standard therapy.

AB - Metastatic colorectal cancer (mCRC) is treated with cetuximab 250 mg/m2 administered weekly over 1 hour or biweekly (q2w) over 3.5 hours when combined with irinotecan. This prospective study investigated cetuximab 500 mg/m2 plus irinotecan 180 mg/m2 administered q2w over 1.5 hours independent of RAS or BRAF mutation status in mCRC patients in a third-line setting. The intention-to-treat population included 181 patients. No patients had complete response, 18% had partial responses (PR) and 48% stable disease (SD). For cetuximab, a relative dose intensity of ≥90% was reached in 78% and for irinotecan in 67% of the patients. Grade 3 to 4 toxicities were pain (17%), fatigue (9%), neutropenia (8%), diarrhea (8%), rash (8%), infection (7%) and hypersensitivity (3%). No deaths occurred. Next-generation sequencing in 96.7% of the patients revealed that 50.3% had RAS and BRAFV600E wild type (WT), with a mutation type (MT) in 45.1% of the RAS and 4.4% of the BRAFV600E genes. In patients with RAS-WT and RAS-MT tumors, a PR was obtained in 32% and 4% (P = .000003) and an SD in 43% and 53%, respectively, with a superior PFS (6.2 vs 3.7 months; hazard ratio [HR] 2.12, P = .00001) and OS (12.9 vs 8.8 months; HR 1.71, P = .0008). Treatment efficacy was poor in 7.4% of patients with an RAS mutation outside KRAS exon 2 and in 38% of patients with KRAS exon 2 mutations. Administration of cetuximab and irinotecan q2w, shortening treatment time from 3.5 to 1.5 hours, is recommended as standard therapy.

KW - cetuximab

KW - colorectal cancer

KW - irinotecan

KW - RAS-mutation

KW - biweekly

UR - http://www.scopus.com/inward/record.url?scp=85098516672&partnerID=8YFLogxK

U2 - 10.1002/ijc.33448

DO - 10.1002/ijc.33448

M3 - Journal article

C2 - 33336394

VL - 148

SP - 2542

EP - 2556

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 10

ER -

ID: 61898703