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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, Richard A., Fisher, David J., Graham, Janet, Seligmann, Jenny F., Seymour, Matthew, Kaplan, Richard, Yates, Emma, Parmar, Mahesh, Richman, Susan D., Quirke, Philip, Butler, Rachel, Brown, Ewan, Collinson, Fiona, Falk, Stephen, Wasan, Harpreet, Shiu, Kai-Keen, Middleton, Gary, Samuel, Leslie, Wilson, Richard H., Brown, Louise C. and Maughan, Timothy S. 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 39 (33) , pp. 3693-3704. 10.1200/JCO.21.01436

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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: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Additional Information: Licensed under the Creative Commons Attribution 4.0 License:
Publisher: American Society of Clinical Oncology
ISSN: 0732-183X
Date of First Compliant Deposit: 1 October 2021
Date of Acceptance: 18 August 2021
Last Modified: 26 Nov 2021 14:41

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