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

Richard A. Adams, David J. Fisher, Janet Graham, Jenny F. Seligmann, Matthew Seymour, Richard Kaplan, Emma Yates, Mahesh Parmar, Susan D. Richman, Philip Quirke, Rachel Butler, Ewan Brown, Fiona Collinson, Stephen Falk, Harpreet Wasan, Kai-Keen Shiu, Gary Middleton, Leslie Samuel, Richard H. Wilson, Louise C. Brown* (Corresponding Author)Timothy S. Maughan, FOCUS Trial Collaboration

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSEDespite 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.METHODSFOCUS4 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.RESULTSBetween 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.CONCLUSIONDespite 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.
Original languageEnglish
Article numberJCO.21.01436
Number of pages42
JournalJournal of Clinical Oncology
Early online date13 Sep 2021
DOIs
Publication statusE-pub ahead of print - 13 Sep 2021

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