Real-world comparison between weekly versus biweekly dosing of cetuximab for metastatic colorectal cancer
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: This real-world study aims to compare overall survival (OS) associated with biweekly (Q2W) versus weekly (Q1W) cetuximab dosing regimens for metastatic colorectal cancer (mCRC) treatment in the US. Methods: Adult patients with KRAS wild-type mCRC who received cetuximab ± chemotherapy from 2013 to 2019 were selected using Flatiron Health's electronic health records database. Propensity score matching was used to balance Q2W and Q1W cohorts on baseline patient characteristics. The Kaplan–Meier method was used for survival analyses. Several sensitivity analyses were conducted to assess the robustness of findings from the main analysis. Results: Of 1075 patients in the study, 60.7% received cetuximab Q1W and 39.3% Q2W. Median OS (95% confidence interval) in months was 17.2 (15.3, 18.8) for Q2W versus 14.3 (12.8, 16.0) for Q1W; p = 0.246. Similar OS between the dosing cohorts was observed in sensitivity analyses. Conclusion: Weekly and biweekly cetuximab had comparable effectiveness in this real-world study.
Supplementary Material
File (supplementary materials.docx)
- Download
- 63.88 KB
References
Papers of special note have been highlighted as: • of interest; •• of considerable interest
1.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J. Clin. 135(05), 584–590 (2022).
2.
Cokkinides V, Albano J, Samuels A, Ward M, Thum J. American Cancer Society: Cancer facts and figures. American Cancer Society, GA, USA (2005).
3.
Wang X-W, Zhang Y-J. Targeting mTOR network in colorectal cancer therapy. World J. Gastroenterol. 20(15), 4178 (2014).
4.
Kindler HL, Shulman KL. Metastatic colorectal cancer. Curr. Treat. Options Oncol. 2(6), 459–471 (2001).
5.
Kurkjian C, Kummar S. Advances in the treatment of metastatic colorectal cancer. Am. J. Ther. 16(5), 412 (2009).
6.
Siegel RL, Miller KD, Fedewa SA et al. Colorectal cancer statistics, 2017. CA Cancer J. Clin. 67(3), 177–193 (2017).
7.
Peeters M, Price T. Biologic therapies in the metastatic colorectal cancer treatment continuum–applying current evidence to clinical practice. Cancer Treat. Rev. 38(5), 397–406 (2012).
• Rationale for using drugs that target epidermal growth factor receptor (EGFR) and improve survival outcomes in patients with mCRC
8.
Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA 325(7), 669–685 (2021).
9.
ERBITUX® (cetuximab). HIGHLIGHTS OF PRESCRIBING INFORMATION. Eli Lilly and Company and ImClone Systems, NJ, USA (2019). www.accessdata.fda.gov/drugsatfda_docs/label/2019/125084s273lbl.pdf
10.
ERBITUX- cetuximab solution [package insert]. ImClone LLC, NJ, USA (2020). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bc6397e-4bd8-4d37-a007-a327e4da34d9
11.
Ocvirk J, Brodowicz T, Wrba F et al. Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial. World J. Gastroenterol. 16(25), 3133 (2010).
12.
European Medicines Agency. Erbitux. Merck Europe B.V (2020). www.ema.europa.eu/en/medicines/human/EPAR/erbitux
• Evidence on previously approved dosing regimens of Cetuximab
13.
US Food & Drug Administration. FDA approves new dosing regimen for cetuximab (2021). www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-new-dosing-regimen-cetuximab#:∼:text=On%20April%206%2C%202021%2C%20the,the%20head%20and%20neck%20(SCCHN
14.
Zhao X, Iqbal S, Valdes IL, Dresser M, Girish S. Integrating real-world data to accelerate and guide drug development: a clinical pharmacology perspective. Clin. Transl. Sci. 15(10), 2293–2302 (2022).
15.
Tabernero J, Pfeiffer P, Cervantes A. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer: an effective, more convenient alternative to weekly administration? Oncologist 13(2), 113–119 (2008).
•• Derived the pharmacokinetics of cetuximab 250 mg/m2 Q1W vs 500 mg/m2 Q2W from 19 clinical studies of patients with various solid tumor types, including colorectal cancer (CRC).
16.
Bokemeyer C, Bondarenko I, Hartmann J et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann. Oncol. 22(7), 1535–1546 (2011).
17.
Hubbard JM, Alberts SR. Alternate dosing of cetuximab for patients with metastatic colorectal cancer. Gastrointest Cancer Res. 6(2), 47–55 (2013).
•• This literature review concluded that cetuximab biweekly dosing is a viable treatment option with a benefit-risk profile comparable to those obtained with weekly dosing.
18.
Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med. 351(4), 337–345 (2004).
19.
Kotake M, Aoyama T, Munemoto Y et al. Multicenter phase II study of infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin, plus biweekly cetuximab as first-line treatment in patients with metastatic colorectal cancer (CELINE trial). Oncol Letters. 13(2), 747–753 (2017).
20.
Pfeiffer P, Nielsen D, Bjerregaard J, Qvortrup C, Yilmaz M, Jensen B. Biweekly cetuximab and irinotecan as third-line therapy in patients with advanced colorectal cancer after failure to irinotecan, oxaliplatin and 5-fluorouracil. Ann. Oncol. 19(6), 1141–1145 (2008).
21.
Mennini FS, Marcellusi A, Fabiano G, Rimassa L, Santoro A, Personeni N. Budget impact of bimonthly use of cetuximab in patients diagnosed with metastatic colorectal cancer. Future Oncol. 15(18), 2107–2112 (2019).
22.
Pescott CP, Boutmy E, Batech M, Ronga P, Lamy F-X. Real-world healthcare resource utilization and costs of weekly versus every-2-week cetuximab in metastatic colorectal cancer. J. Comp. Eff. Res. 10(5), 353–364 (2021).
•• This article reports the real-world healthcare resource utilization of biweekly vs weekly dosing regimen of cetuximab in mCRC treatment
23.
Matsuda A, Yamada T, Jamjittrong S et al. Comparison between biweekly and weekly cetuximab in patients with metastatic colorectal cancer: a meta-analysis. Anticancer Res. 40(6), 3469–3476 (2020).
24.
Ma X, Long L, Moon S, Adamson BJS, Baxi SS. Comparison of Population Characteristics in Real-World Clinical Oncology Databases in the US: Flatiron Health, SEER, and NPCR. www.medrxiv.org/content/10.1101/2020.03.16.20037143v1.full.pdf
25.
Birnbaum B, Nussbaum N, Seidl-Rathkopf K et al. Model-assisted cohort selection with bias analysis for generating large-scale cohorts from the EHR for oncology research. https://arxiv.org/ftp/arxiv/papers/2001/2001.09765.pdf
26.
Zhang Q, Gossai A, Monroe S, Nussbaum NC, Parrinello CM. Validation analysis of a composite real-world mortality endpoint for patients with cancer in the United States. Health Serv. Res. 56(6), 1281–1287 (2021).
27.
Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 10(2), 150–161 (2011).
28.
VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Ann. Intern. Med. 167(4), 268–274 (2017).
29.
Hainmueller J. Entropy balancing for causal effects: a multivariate reweighting method to produce balanced samples in observational studies. Politic Analysis 20(1), 25–46 (2012).
30.
Van Cutsem E, Köhne C-H, Láng I et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J. Clin. Oncol. 29(15), 2011–2019 (2011).
31.
Van Cutsem E, Lenz HJ, Köhne CH et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J. Clin. Oncol. 33(7), 692–700 (2015).
32.
Bokemeyer C, Van Cutsem E, Rougier P et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur. J. Cancer 48(10), 1466–1475 (2012).
33.
Kasper S, Foch C, Messinger D et al. Noninferiority of cetuximab every-2-weeks versus standard once-weekly administration schedule for the first-line treatment of RAS wild-type metastatic colorectal cancer. Eur. J. Cancer 144, 291–301 (2021).
34.
Brodowicz T, Ciuleanu TE, Radosavljevic D et al. FOLFOX4 plus cetuximab administered weekly or every second week in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer: a randomized phase II CECOG study. Ann. Oncol. 24(7), 1769–1777 (2013).
• They demonstrated that the combination of cetuximab biweekly with FOLFOX4 was comparable with the efficacy and safety profile observed for FOLFOX4 plus standard weekly cetuximab in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer.
35.
Mrabti H, De la Fouchardiere C, Desseigne F et al. Irinotecan associated with cetuximab given every 2 weeks versus cetuximab weekly in metastatic colorectal cancer. J. Cancer Res. Ther. 5(4), 272–276 (2009).
36.
Lamy F-X, Batech M, Boutmy E, Ronga P, Salim S, Pescott CP. Comparative effectiveness of weekly versus every-2-weeks cetuximab in metastatic colorectal cancer in a US-insured population. J. Comp. Eff. Res. 9(16), 1117–1129 (2020).
37.
Zekri J, Farag K, Al-Saadi R, Ashour M, Haggag R. Safety and efficacy of biweekly cetuximab based chemotherapy for patients with metastatic colorectal cancer. J. Unexplored Med. Data 1, 15–20 (2016).
• This paper validates the tolerability and efficacy of 500 mg/m biweekly cetuximab for patients with metastatic colorectal cancer.
38.
Tabernero J, Ciardiello F, Rivera F et al. Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Ann. Oncol. 21(7), 1537–1545 (2010).
Information & Authors
Information
Published In
Copyright
© 2023 Eli Lilly and Company. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License
History
Received: 8 August 2022
Accepted: 9 January 2023
Published online: 27 January 2023
Keywords:
Topics
Authors
Funding Information
Metrics & Citations
Metrics
Article Usage
Article usage data only available from February 2023. Historical article usage data, showing the number of article downloads, is available upon request.
Citations
How to Cite
Real-world comparison between weekly versus biweekly dosing of cetuximab for metastatic colorectal cancer. (2023) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2022-0143
Export citation
Select the citation format you wish to export for this article or chapter.
Citing Literature
- Jennifer S. Wang, Benny Johnson, Caitlin C. Murphy, Racial, Ethnic, and Socioeconomic Survival Disparities in Early-Onset Metastatic Colorectal Cancer, JAMA Network Open, 10.1001/jamanetworkopen.2025.53146, 9, 1, (e2553146), (2026).
- Bazarbashi Shouki, Alnajjar Abdelsalam, Al Sharm Abdullah, Alshammari Kanan, Al Sherhi Ahmed, Dawoud Emad, Heinemann Volker, Aseafan Mohamed, Chehal Aref, Alghamdi Mohammed, Hamza Dina, Khoury Maroun, Venniyoor Ajit, Mahrous Mervat, Rasul Kakil, Elsamany Shereef, Trad Diaeddine, Management of metastatic colorectal cancer: consensus in the Gulf Cooperation Council countries, Therapeutic Advances in Medical Oncology, 10.1177/17588359241299324, 17, (2025).
- Lan Ni, Azhar Zaman Khan, Amanda Long, Ling Gao, Nikki Toms, Elena Gonzalez‐Gugel, Susan Holsmer‐Brand, Yong Lin, Paolo Abada, Sandra Dickin, Declan O'Dea, Ran Wei, Min‐Hua Jen, Himani Aggarwal, Optimizing the Dosing Regimen of Cetuximab and Ramucirumab Using the Model‐Informed Drug Development Paradigm, Clinical Pharmacology & Therapeutics, 10.1002/cpt.2919, 114, 1, (77-87), (2023).