The incidence of EOCRC, defined as CRC diagnosed in pts< 50 years old, is increasing. Current literature relating to the palliative systemic tx used, its efficacy, tolerability and outcomes in this group is sparse.
Retrospective analysis of pts with mEOCRC treated with systemic tx at the Royal Marsden Hospital (RMH) between Jan 2009 – Dec 2014 was conducted.
114 pts had palliative systemic tx. 93 had mEOCRC at diagnosis of whom 51% were male, median age 43 (range 21-49), 90% performance status ≤1. 72% had left (L) sided tumours. 4% had signet cells. 2 pts had known hereditary syndromes. 72% had liver, 20% peritoneal and 20% lung metastases (met). All 114 pts had ≥1 line of doublet cytotoxic tx. The most commonly administered regimens were: 15% FOLFIRI+ bevacizumab (Bev), 15% FOLFIRI, 11% CAPOX, 10% FOLFOX+ Bev. 12% of tx was given within trials. 38% of pts had tx delays and 38% dose reductions or one agent of a combination tx discontinued early, during their the first line tx. 19% had radiofrequency ablation to liver or lung met. Median overall survival (mOS) in pts presenting with mEOCRC: 18.5 months (95% C.I 14.3-22.6). In addition to BRAF mutant pts, the groups below also trended towards a lower mOS, months (95%C.I): -Younger age: Age 20-29=8.3 (2.6-28.6), 30-39=16.1 (9.6-22.6), 40-49=21.2 (14.9-27.7) -Right (R) sided tumour: R = 13.7 (8.3-18.7) vs L = 20.2 (14.9-27.7) -Signet cells =7.0 (NA) vs No signet cells =18.7 (14.3-22.6) -Fewer lines of systemic tx (Table) The majority of KRAS Wild Type (WT) pts (n = 46) had cetuximab or panitumumab. mOS was 21.7 months (95% C.I 16.0-27.7) for WT vs 15.8 months (95% C.I 9.9-21.2) in mutant pts.Table:
|Metastatic tx line||1||2||3||4|
|Median PFS, months||6.9||5.0||2.0||3.9|
|Best Response (%)||CR 4 PR 40 SD 23 PD 32 NA 1||CR 1 PR 17 SD 26 PD 51 NA 5||PR 8 SD 23 PD 69||PR 7 SD 13 PD 73 NA 7|
|mOS from diagnosis if last line of tx, months||9.0||14.9||18.7||31.7|
Pts treated with sequential combination systemic tx had a better mOS. However, pts with mEOCRC appear to have lower response rates, progression free survival (PFS) and OS when compared to recently published randomised trials. This suggests a more aggressive disease phenotype that warrants further research and tx development.
Clinical trial identification
Legal entity responsible for the study
Royal Marsden Hospital, UK
All authors have declared no conflicts of interest.