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

Brodowicz, Thomas; Ciuleanu, Tudor-Eliade; Radosavljević, Davorin; Shacham‐Shmueli, Einat; Vrbanec, Damir; Plate, S.; Mrsic-Krmpotic, Zrinka; Dank, M.; Purkalne, Gunta; Messinger, Diethelm; Zielinski, Christoph

doi:10.1093/annonc/mdt116

Cited by 53 publications

(61 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors concluded that the activity and safety of FOLFOX plus either cetuximab administered weekly or biweekly were similar. [18] In the Medical Research Council COIN trial, 1,630 patients were randomly assigned to treatment groups: 815 to oxaliplatin and 5 FU chemotherapy (FOLFOX or XELOX; arm A) and 815 to the same combinations plus cetuximab (arm B). Tumour samples from 1,316 (81%) patients were used for somatic molecular analyses; 565 (43%) had K-RAS mutations.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of biweekly cetuximab based chemotherapy for patients with metastatic colorectal cancer

Zekri¹,

Farag²,

Al-Saadi³

et al. 2016

JUMD

View full text Add to dashboard Cite

How to cite this article: Zekri J, Farag K, Al-Saadi R, Ashour M, Haggag R. Safety and efficacy of biweekly cetuximabbased chemotherapy for patients with metastatic colorectal cancer. J Unexplored Med Data 2016;1:15-20. Aim:Cetuximab was administered weekly in registration clinical trials. Biweekly administration is more convenient when combining cetuximab with biweekly chemotherapy in patients with metastatic colorectal cancer (mCRC). The aim of this study is to evaluate safety and efficacy of biweekly cetuximab at a dose of 500 mg/m 2 with chemotherapy in routine clinical practice. Methods: Clinical data of 19 consecutive patients with K-RAS wild type mCRC who received biweekly cetuximab with biweekly fluropyrimidine based chemotherapy were reviewed. Toxicity assessment was limited to the first 6 cycles of treatment. Best tumor response was assessed by an independent radiologist. Results: Median age was 59 (24-74) years. Cetuximab was administered in first, second and third line settings in 7, 9 and 3 patients respectively. Grade I/II cetuximab specific adverse events (AEs) were skin rash (47.3%), diarrhea (21%), infusion reactions (10.5%), Hypomagnesaemia (10.5%) and nail disorders (5%). Grade III AEs were skin rash (10.5%) and diarrhea (5.3%). There was no grade IV AEs. There were no complete responders. Partial response was achieved in 8 (42.1%) and stable disease in 6 (31.5%) patients. Conclusion: This small but real life experience shows that biweekly cetuximab with chemotherapy is safe and effective. The frequency of AEs compares favorably to weekly administration reported in the literature. These finding add to the relatively limited available data on biweekly administration to support its adoption in routine clinical practice. ABSTRACT

show abstract

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of biweekly cetuximab based chemotherapy for patients with metastatic colorectal cancer

Zekri¹,

Farag²,

Al-Saadi³

et al. 2016

JUMD

View full text Add to dashboard Cite

show abstract

“…Biweekly administration is not included in the SPC for cetuximab. We consider the RCT by Brodowicz et al 166 to be of sufficient quality to make this claim and believe the claim of equivalence to be reasonable.…”

Section: Drug Acquisition Costsmentioning

confidence: 91%

“…Cetuximab was assumed to be administered on a biweekly schedule to coincide with FOLFOX/FOLFIRI administration, as this is common clinical practice within the NHS. In addition, Merck Serono argued, on the basis of an open-label RCT by Brodowicz et al 166 and a literature review, 167 that biweekly administration of 500 mg/m 2 of cetuximab is equivalent to induction with 400 mg/m 2 followed by weekly administration of 250 mg/m 2 . Biweekly administration is not included in the SPC for cetuximab.…”

Section: Drug Acquisition Costsmentioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation

Huxley

Crathorne

Varley-Campbell

et al. 2017

Health Technol Assess

View full text Add to dashboard Cite

BackgroundColorectal cancer is the fourth most commonly diagnosed cancer in the UK after breast, lung and prostate cancer. People with metastatic disease who are sufficiently fit are usually treated with active chemotherapy as first- or second-line therapy. Targeted agents are available, including the antiepidermal growth factor receptor (EGFR) agents cetuximab (Erbitux®, Merck Serono UK Ltd, Feltham, UK) and panitumumab (Vecitibix®, Amgen UK Ltd, Cambridge, UK).ObjectiveTo investigate the clinical effectiveness and cost-effectiveness of panitumumab in combination with chemotherapy and cetuximab in combination with chemotherapy for rat sarcoma (RAS) wild-type (WT) patients for the first-line treatment of metastatic colorectal cancer.Data sourcesThe assessment included a systematic review of clinical effectiveness and cost-effectiveness studies, a review and critique of manufacturer submissions, and a de novo cohort-based economic analysis. For the assessment of effectiveness, a literature search was conducted up to 27 April 2015 in a range of electronic databases, including MEDLINE, EMBASE and The Cochrane Library.Review methodsStudies were included if they were randomised controlled trials (RCTs) or systematic reviews of RCTs of cetuximab or panitumumab in participants with previously untreated metastatic colorectal cancer withRASWT status. All steps in the review were performed by one reviewer and checked independently by a second. Narrative synthesis and network meta-analyses (NMAs) were conducted for outcomes of interest. An economic model was developed focusing on first-line treatment and using a 30-year time horizon to capture costs and benefits. Costs and benefits were discounted at 3.5% per annum. Scenario analyses and probabilistic and univariate deterministic sensitivity analyses were performed.ResultsThe searches identified 2811 titles and abstracts, of which five clinical trials were included. Additional data from these trials were provided by the manufacturers. No data were available for panitumumab plus irinotecan-based chemotherapy (folinic acid + 5-fluorouracil + irinotecan) (FOLFIRI) in previously untreated patients. Studies reported results forRASWT subgroups. First-line treatment with anti-EGFR therapies in combination with chemotherapy appeared to have statistically significant benefits for patients who areRASWT. For the independent economic evaluation, the base-case incremental cost-effectiveness ratio (ICER) forRASWT patients for cetuximab plus oxaliplatin-based chemotherapy (folinic acid + 5-fluorouracil + oxaliplatin) (FOLFOX) compared with FOLFOX was £104,205 per quality-adjusted life-year (QALY) gained; for panitumumab plus FOLFOX compared with FOLFOX was £204,103 per QALY gained; and for cetuximab plus FOLFIRI compared with FOLFIRI was £122,554 per QALY gained. The ICERs were sensitive to treatment duration, progression-free survival, overall survival (resected patients only) and resection rates.LimitationsThe trials includedRASWT populations only as subgroups. No evidence was available for panitumumab plus FOLFIRI. Two networks were used for the NMA and model, based on the different chemotherapies (FOLFOX and FOLFIRI), as insufficient evidence was available to the assessment group to connect these networks.ConclusionsAlthough cetuximab and panitumumab in combination with chemotherapy appear to be clinically beneficial forRASWT patients compared with chemotherapy alone, they are likely to represent poor value for money when judged by cost-effectiveness criteria currently used in the UK. It would be useful to conduct a RCT in patients withRASWT.Study registrationThis study is registered as PROSPERO CRD42015016111.FundingThe National Institute for Health Research Health Technology Assessment programme.

show abstract

“…In clinical studies performed in mCRC, biweekly cetuximab up to 700 mg/m 2 (q2w) showed a safety profile similar to that described for the weekly administration [18]. Overall, different clinical studies (a phase I study, several controlled and non-controlled phase II studies, and retrospective studies) concluded that in patients with mCRC, cetuximab q2w combined with chemotherapy (CT) regimens was feasible and may be as effective and safe as the standard weekly schedule [13,20,21].…”

Section: Discussionmentioning

confidence: 92%

Maintenance Therapy with Biweekly Cetuximab: Optimizing Schedule Can Preserve Activity and Improves Compliance in Advanced Head and Neck Cancer

et al. 2018

View full text Add to dashboard Cite

Objectives: This study evaluates maintenance cetuximab administered every 2 weeks (q2w) after chemotherapy plus cetuximab as first-line treatment in a series of patients with head and neck squamous cell cancer and compares the results with those obtained in a historical control group of patients receiving weekly cetuximab. Methods: After chemotherapy plus cetuximab as first-line treatment, in Group A, 36 patients enrolled from October 2016 to November 2017, received biweekly cetuximab, administered at 500 mg/m². Group B was a control group of patients treated at our institution from August 2015 to September 2016 and received weekly infusion of cetuximab at 250 mg/m². Results: Confirmed overall response rates were, respectively, 19% for Group A and 17% for Group B according to intention-to-treat analysis. During the maintenance treatment, median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 4.8 and 4.4 months; OS, 9.0 and 7.9 months; in Groups A and B, respectively). The most common adverse events among treated subjects included fatigue, rash, and hypomagnesemia. Conclusion: Maintenance therapy with simplified biweekly cetuximab is a convenient, effective, and well-tolerated regimen in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

show abstract

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

Abstract: Activity and safety of FOLFOX4 plus either cetuximab administered weekly or every second week were similar.

Cited by 53 publications

References 32 publications

Safety and efficacy of biweekly cetuximab based chemotherapy for patients with metastatic colorectal cancer

Safety and efficacy of biweekly cetuximab based chemotherapy for patients with metastatic colorectal cancer

The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation

Maintenance Therapy with Biweekly Cetuximab: Optimizing Schedule Can Preserve Activity and Improves Compliance in Advanced Head and Neck Cancer

Contact Info

Product

Resources

About