FOCUS4-N: trial results and individual patient data meta-analysis of maintenance therapy versus active monitoring for patients with first line metastatic colorectal cancer


Session type:

Richard Adams1, David Fisher2, Janet Graham3, Jenny Seligmann4, Matt Seymour4, Richard Kaplan2, Emma Yates2, Susan Richman4, Philip Quirke4, Rachel Butler5, Ewan Brown6, Stephen Falk7, Fiona Collinson4, Richard Wilson8, Louise Brown2, Tim Maughan9
1Cardiff University, 2Medical Research Council (MRC) – Clinical Trials Unit, 3Beatson West of Scotland Cancer Centre, 4University of Leeds, 5North Bristol NHS Trust, 6NHS Lothian, 7University Hospitals Bristol NHS Foundation Trust, 8University of Glasgow, 9University of Oxford



Optimising treatment strategies for patients with mCRC responding to first line chemotherapy has important connotations for quality of life, toxicity and prudent health care. Current standards in national guidelines support a strategy of ongoing chemotherapy until disease progression or excess toxicity. Trial level meta-analysis has indicated that complete treatment breaks may not detrimentally affect outcome however, breaks from treatment are not universally offered. FOCUS4-N explores the impact of oral capecitabine (C) maintenance in patients (pts) who are responding to first line therapy. Results are explored in parallel to an IPDM of maintenance or active monitoring (AM).


FOCUS4 was a molecularly stratified trial programme that registered pts with newly diagnosed mCRC. Pts were randomised 1:1 after 16 wks of first line therapy between maintenance C or AM. Primary outcome was PFS assessed using 8-wkly RECIST CT scans, OS was a secondary outcome. Toxicity/tolerability were assessed 4-weekly. Cox regression was used to assess efficacy. An IPDM of intermittent strategy impact on survival was undertaken. Intermittent strategies were classified into two groups: a planned stopping of all therapy (AM strategy; 6 trials; 2,907 pts) or to the same treatment omitting oxaliplatin (maintenance strategy; 3 trials; 1,271 pts).


From Mar 2014 to Mar 2020, 254 pts were randomised (127 to C, 127 to AM). Baseline characteristics were balanced. PFS HR=0.38 (0.29-0.5) p=<0.001; OS HR=0.93 (0.69, 1.27) p=0.66. Toxicity from C was as expected with fatigue, diarrhoea and hand-foot syndrome most common. IPDM of AM versus continuous therapy demonstrated no detriment in OS HR=1.03 [0.93-1.14], whether from complete break HR 1.04 [0.87-1.26] or maintenance strategies (HR 0.99 [0.87-1.13]).


Despite strong evidence of disease control with maintenance therapy, OS remains unaffected, FOCUS4-N provides additional evidence to support the IPDM of international trials. The use of treatment breaks is a safe alternative for patients who are stable or responding well to first line treatment for mCRC.

Impact statement

Intermittent treatment with either complete treatment breaks or with therapy de-escalation (e.g. omission of oxaliplatin) are safe alternatives to continuous treatment for patients who have stable or responding disease after 12 to 24 weeks of first-line treatment for metastatic colorectal cancer.