Noninferiority of cetuximab every-2-weeks versus standard once-weekly administration schedule for the first-line treatment of RAS wild-type metastatic colorectal cancer
Journal
European Journal of Cancer
Journal Volume
144
Pages
291-301
Date Issued
2021
Author(s)
Kasper S.
Foch C.
Messinger D.
Esser R.
Lamy F.-X.
Rothe V.
Chen W.
Rouyer M.
Brodowicz T.
Zielinski C.
Abstract
Aim: This study assessed whether cetuximab 500 mg/m2 administered every 2 weeks (Q2W), when combined with chemotherapy as a first-line (1L) treatment, was noninferior to the approved dose (400 mg/m2 followed by 250 mg/m2 once weekly [Q1W]) for overall survival (OS) in adults with RAS wild-type metastatic colorectal cancer (mCRC). Methods: This pooled analysis included patients receiving 1L treatment with cetuximab Q1W or Q2W in combination with chemotherapy from post-authorisation studies with patient-level data available to the sponsor. Baseline characteristics were adjusted with a propensity score using inverse probability of treatment weighting (IPTW). Noninferiority in terms of OS was tested with a noninferiority margin for the hazard ratio (HR) of 1.25 using a Cox proportional hazards regression model. Secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and rates of lung/liver metastases resection and serious adverse events. Results: OS time was noninferior in the Q2W cohort (n = 554) compared to the Q1W cohort (n = 763), with a HR after IPTW (95% confidence interval) of 0.827 (0.715–0.956) and median OS times of 24.7 (Q1W) and 27.9 (Q2W) months. There were no major differences in PFS (HR: 0.915 [0.804–1.042]). The odds ratios (ORs) after IPTW for ORR (1.292 [1.031–1.617]) and the rates of lung/liver metastases resection (1.419 [1.043–1.932]) favoured the Q2W regimen. No differences were noted in the occurrence rate of any SAE between groups; the OR after IPTW was 1.089 (0.858–1.382). Conclusions: The cetuximab Q2W regimen was noninferior to the Q1W regimen for OS in the 1L treatment of mCRC. ? 2020 The Authors
Subjects
Administration schedule; Cetuximab; Metastatic colorectal cancer; Noninferiority; Overall survival; Pooled analysis
SDGs
Other Subjects
cetuximab; fluoropyrimidine; fluorouracil; folinate calcium; folinic acid; irinotecan; oxaliplatin; Ras protein; antineoplastic agent; cetuximab; fluorouracil; folinic acid; Ras protein; adult; aged; anorexia; Article; cancer combination chemotherapy; cohort analysis; colitis; controlled study; diarrhea; drug efficacy; enteritis; female; human; infusion related reaction; leukopenia; liver metastasis; liver resection; lung metastasis; lung resection; major clinical study; male; meta analysis; metastatic colorectal cancer; mucosa inflammation; nausea and vomiting; overall response rate; overall survival; priority journal; progression free survival; skin infection; skin manifestation; treatment response; colorectal tumor; comparative study; drug administration; equivalence trial (topic); follow up; genetics; metastasis; middle aged; pathology; prognosis; survival rate; Aged; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; Drug Administration Schedule; Equivalence Trials as Topic; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Prognosis; ras Proteins; Survival Rate
Publisher
Elsevier Ltd
Type
journal article