Abstract 455P
Background
Cetuximab (CET) is approved in the US for K-RAS wild type, EGFR-expressing, metastatic colorectal cancer (mCRC) and squamous cell carcinoma of head and neck with loading dose of 400 mg/m2 followed by weekly (Q1W) 250 mg/m2. In practice, CET 500 mg/m2 plus chemotherapy biweekly (Q2W) is commonly used and recommended by current guidelines. We designed this meta-analysis to validate the efficacy and safety between Q2W vs. Q1W CET dosing.
Methods
A systematic literature review was performed on Pubmed and RightFind between 2007-2017 for patients with K-RAS wild type mCRC who received Q2W or Q1W CET and other treatment regimens. Observational studies and case reports were excluded. Both randomized trials that compared Q2W and Q1W CET dosing and single arm trials with only Q2W CET schedule were included. CRYSTAL (a phase III study with Q1W CET) was paired to each single arm study and reweighted to achieve similar demographic and baseline characteristics. We analyzed OS and PFS with hazard ratios, ORR with odd ratios, and risk difference of adverse events (AE) of special interest (based on US label safety profile) between Q2W and Q1W CET dosing groups.
Results
Six studies were identified from the systemic literature review for our meta-analysis; one phase II randomized study with Q1W and Q2W schedules (n=152), four phase II single arm studies with Q2W schedule (n=448), and NORDIC 7.5 phase II study (Q2W, n=152) paired with NORDIC VII phase III study arm C (Q1W, n=109). Efficacy was similar comparing Q2W CET vs. Q1W CET in patients with K-RAS wide type mCRC; OS HR = 0.96, 95% CI [0.89, 1.04], PFS HR = 0.96, 95% CI [0.87, 1.05]; ORR odds ratio 1.16, 95% CI [0.96, 1.41]. Mean differences (Q2W CET – Q1W CET) across the rates of AEs with special interest were not clinically meaningful with no obvious directionality : paronychia +6.2%, neutropenia +4.0%, diarrhea -4.6%, acne-like rash -1.0%, rash -3.1%, dermatitis acneiform -1.0%, palmar-plantar erythrodysesthesia syndrome -0.8%, cardiopulmonary arrest -4.1%, infusion related reaction +0.7%, hypomagnesemia +0.7%, nail toxicity -1.2% and sepsis +1.9%.
Conclusions
This meta-analysis suggests no significant differences in efficacy and safety between Q2W vs. Q1W CET dosing in patients with K-RAS wild type mCRC.
Clinical trial identification
Editorial acknowledgement
Trish Huynh (Eli Lilly and Company, Indianapolis, IN) provided writing assistance.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
A. Parikh: Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly and Company; Advisory/Consultancy: Puretech; Research grant/Funding (institution): Guardant; Research grant/Funding (institution): Bristol Myers Squibb; Research grant/Funding (institution): Array; Research grant/Funding (institution): Plexxicon; Research grant/Funding (institution): Novartis. E.G. Gugel, N. Smolyakova, M-H. Jen, J.S. Kim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. N. Toms, Y. Lin: Full/Part-time employment: Eli Lilly and Company. S. Kopetz: Shareholder/Stockholder/Stock options: MolecularMatch; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): EMD Serono; Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Karyopharm Therapeutics; Advisory/Consultancy: Amal Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Navire Pharma; Advisory/Consultancy: Symphogen; Advisory/Consultancy: Holy Stone; Advisory/Consultancy, Research grant/Funding (institution): Biocartis; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly and Company; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy: Astrazeneca/MedImmune; Advisory/Consultancy: Bayer Health; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Redx Pharma; Advisory/Consultancy: Ipsen; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Natera; Advisory/Consultancy: HalioDx; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): MedImmune.