Capecitabine versus active monitoring in stable or responding metastatic colorectal cancer after 16 weeks of first-line therapy: results of the randomized FOCUS4-N trial

Adams, R. A. et al. (2021) Capecitabine versus active monitoring in stable or responding metastatic colorectal cancer after 16 weeks of first-line therapy: results of the randomized FOCUS4-N trial. Journal of Clinical Oncology, (doi: 10.1200/JCO.21.01436) (PMID:34516759) (Early Online Publication)

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Purpose: Despite extensive randomized evidence supporting the use of treatment breaks in metastatic colorectal cancer (mCRC), they are not universally offered to patients despite improvements in quality of life without detriment to overall survival (OS). FOCUS4-N was set up to explore the impact of oral maintenance therapy in patients who are responding to first-line therapy. Methods: FOCUS4 was a molecularly stratified trial program that registered patients with newly diagnosed mCRC. The FOCUS4-N trial was offered to patients in whom a targeted subtrial was unavailable or biomarker tests failed. Patients were randomly assigned using a 1:1 ratio between maintenance capecitabine and active monitoring (AM). The primary outcome was progression-free survival (PFS) with secondary outcomes including OS toxicity and tolerability. Results: Between March 2014 and March 2020, 254 patients were randomly assigned (127 to capecitabine and 127 to AM) across 88 UK sites. Baseline characteristics were balanced. There was strong evidence of efficacy for PFS (hazard ratio = 0.40; 95% CI, 0.21 to 0.75; P < .0001), but no significant improvement in OS (hazard ratio, 0.93; 95% CI, 0.69 to 1.27; P = .66) was observed. Compliance with treatment was good, and toxicity from capecitabine versus AM was as expected with grade ≥ 2 fatigue (25% v 12%), diarrhea (23% v 13%), and hand-foot syndrome (26% v 3%). Quality of life showed little difference between the groups. Conclusion: Despite strong evidence of disease control with maintenance therapy, OS remains unaffected and FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for mCRC. Capecitabine without bevacizumab may be used to extend PFS in the interval after 16 weeks of first-line therapy.

Item Type:Articles
Additional Information:Supported by Cancer Research UK and the National Institute for Health Research (NIHR).
Status:Early Online Publication
Glasgow Author(s) Enlighten ID:Wilson, Professor Richard and Graham, Dr Janet
Authors: Adams, R. A., Fisher, D. J., Graham, J., Seligmann, J. F., Seymour, M., Kaplan, R., Yates, E., Parmar, M., Richman, S. D., Quirke, P., Butler, R., Brown, E., Collinson, F., Falk, S., Wasan, H., Shiu, K.-K., Middleton, G., Samuel, L., Wilson, R. H., Brown, L. C., and Maughan, T. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Clinical Oncology
Publisher:American Society of Clinical Oncology
ISSN (Online):1527-7755
Published Online:13 September 2021
Copyright Holders:Copyright © 2021 American Society of Clinical Oncology
First Published:First published in Journal of Clinical Oncology 2021
Publisher Policy:Reproduced under a Creative Commons License
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