Abstract 431P
Background
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 survival, 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).
Methods
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).
Results
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]).
Conclusions
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.
Clinical trial identification
ISRCTN#90061546.
Editorial acknowledgement
Legal entity responsible for the study
University of Oxford.
Funding
AstraZeneca.
Disclosure
R.A. Adams: Financial Interests, Personal, Invited Speaker, speakers fees: Amgen; Financial Interests, Personal, Other, Travel and conference fees: Servier; Financial Interests, Personal, Advisory Board: AstraZeneca; Merck Serono; Financial Interests, Institutional, Research Grant, investigator led clinical trial: MSD; AstraZeneca; Pfizer. J. Graham: Financial Interests, Personal, Sponsor/Funding: Nucana; Merck Serono; BMS; Bayer; Financial Interests, Personal, Advisory Board: Merck Serono. J. Seligmann: Financial Interests, Personal, Advisory Board: Pierre Fabre; Roche Molecualr Diagnostics; Financial Interests, Personal, Sponsor/Funding: Pierre Fabre; Merck Serono; Servier; Financial Interests, Personal, Speaker’s Bureau: Amgen. R.S. Kaplan: Financial Interests, Institutional, Research Grant: AstraZeneca. P. Quirke: Financial Interests, Personal, Advisory Board: Roche; Adlai Nortye; Avacta Life Sciences; Amgen; Bayer; Financial Interests, Personal, Sponsor/Funding: Roche; Bayer; Amgen; Financial Interests, Personal, Licensing Fees: Roche; Financial Interests, Personal and Institutional, Research Grant: Roche; GeneFirst; ONI. S. Falk: Financial Interests, Personal, Invited Speaker: Merck Serono; Servier; Amgen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Sponsor/Funding: Celgene; Financial Interests, Personal, Stocks/Shares: GSK; Financial Interests, Institutional, Research Grant: Gilead Sciences; Financial Interests, Personal, Other: Servier. R. Wilson: Financial Interests, Personal, Advisory Board: Amgen; Pierre Fabre; CV6 therapeutics; Financial Interests, Personal, Sponsor/Funding: Servier; Amgen; BMS. T. Maughan: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: Vertex; Pierre Fabre; Financial Interests, Institutional, Research Grant: AstraZeneca; PsiOxus; Merck KGgA; Almac.All other authors have declared no conflicts of interest.