P-287 - Is second line aflibercept and FOLFIRI a tolerable and useful down-staging schedule in Ras mutant advanced colorectal cancer in a real world environ...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Cytotoxic agents
Colon and Rectal Cancer
Biological therapy
Presenter A. Vinayan
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors A. Vinayan1, R. Glynne-Jones2, K. Ocwzarczyk1, M. Harrison1, K. Kanthilal1
  • 1Mount Vernon Cancer Centre, London/UK
  • 2Mount Vernon Centre for Cancer Treatment, London/UK



In a phase III randomized trial [1], aflibercept added to FOLFIRI significantly improved overall survival (OS) in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin compared to FOLFIRI alone. The Cancer Drug Fund in 2014 approved the use of aflibercept in the UK, under this indication. Overall response rate (ORR) was noted to be doubled suggesting that the regimen could be a useful down-staging treatment option for selected patients with RAS mutations. This advantage should be balanced against increased chemotherapy toxicity. More than 25% of patients discontinued treatment due to adverse effects (AE) (and a further 13.6% by patients' choice) with the majority of AE occurring in the first 3 courses.


We carried out a single center, retrospective analysis of the use of aflibercept with FOLFIRI second line after treatment with oxaliplatin to determine the ORR, and frequency and causes for early versus late aflibercept discontinuation in an unselected patient population.


Between June 2013 and December 2014, 51 patients were treated in our center with aflibercept and FOLFIRI as second line. Median patient age was 62 (range 31-81) with the majority of patients being ECOG performance status (PS) 0 or 1. First line chemotherapy had been was administered in an adjuvant setting in 35% of patients. 74% of patients treated with aflibercept had liver metastases. RAS mutation status was available in 40% of patients.

Median number of aflibercept cycles administered per patient was 5 (range 1-21) with 21/51 (44%) patients receiving less than 4 cycles of treatment. Dose reduction was carried out in 29% (15/51) patients and treatment delays occurred in 73% (37/51) patients.

There were no significant differences in age, PS, site of primary, number of metastatic sites, prior chemotherapy including prior treatment with bevacizumab and pelvic radiotherapy between patients who discontinued treatment early (<4 cycles) versus all others.

In patients who were able to continue with aflibercept beyond 4 cycles, 65% (17/26) achieved a documented radiological response and a further 12% (3/26) had stable disease.

ORR in patients with RAS mutation was 54% (7/13) in all-comers and 75% (6/8) in subjects who continued on Aflibercept beyond 4 cycles.

Furthermore, 7 out of 26 patients who continued on Aflibercept were down-staged to enable curative surgery.


This real-world, single center retrospective analysis of aflibercept treatment in an unselected patient population confirms both, the benefit of aflibercept in terms of ORR, as well as its significant AE profile resulting in over 40% of patients discontinuing treatment early. Patients with RAS mutations (ie not eligible for EGFR inhibition) appear to benefit similarly to overall results of the VELOUR trial. Further trials are needed to guide physicians towards a more individualized use of aflibercept and the doses of FOLFIRI in patients with mCRC.