Results from the MRC COIN trial of first-line therapy for advanced colorectal cancer (aCRC)
Tim Maughan
Cardiff University, UK
Background
The MRC COIN trial addresses two questions for aCRC patients
(pts).
Method
Pts
had measurable, inoperable ACRC; no prior CT for metastases; WHO Performance
Status (PS) 0-2 and good organ function. Randomisation was 1:1:1 among 3
treatment arms; A: cOxFp (Ox + fluorouracil/ leucovorin (OxFU) q2w or +
Capecitabine (OxCap) q3w), until progression; B: cOxFp + weekly C; C: iOxFp,
same regimen for 3 months initially, with further 3-month courses upon progression.
Pts/clinicians chose Fp before randomisation.
Results
2445 pts were randomised between 03/05 and 05/08 from 109 UK and Irish hospitals). Median age was 63 years, 92% pts had PS 0-1, 65% received OxCap;
35% OxFU.
A vs C: iOxFp pts had less G3/4 HFS and PNP (p<0.001). Intention-to-treat (ITT) analysis shows a 9% increase in hazard of death in iOxFp pts (HR 1.09, one-sided upper 90% CI 1.17; just exceeding pre-specified boundary of 1.162). Median cOxFp OS 15.6months (mo) vs 14.3mo on iOxFp. Estimated 2-yr survival 28.3% with cOxFp and 26.1% with iOxFp. In per-protocol analysis (PPA, n=1103) the HR is 1.10 with upper 90% CI of 1.21; median OS on cOxFp 19.1mo vs 17.6mo on iOxFp. Estimated 2-yr survivals are 34.8% and 31.1% for cOxFp and iOxFp respectively.
Conclusion
A vs B: Efficacy analyses by KRAS status will be
reported at the conference. A vs C: An estimated difference favouring cOxFp of
1.3mo in median survival was observed indicating that a priori specified
non-inferiority cannot be confirmed. We can reliably exclude a detriment of
>2.3mo in median survival with iOxFp in ITT population (3.3mo in PPA). These
small survival differences must be balanced against reduced toxicity observed
with iOxFp.
Declaration of competing interest for Tim Maughan: Tim Maughan is a member of the Merck Serono Advisory Board.
