516P - A randomized study of KRAS-stratified maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first line induction treatme...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Helga Hagman
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors H. Hagman1, J. Frödin2, A.M. Berglund3, J. Sundberg4, L.W. Vestermark5, M. Albertsson6, E. Fernebro7, A. Johnsson4
  • 1Department Of Oncology, County Hospital Ryhov, SE-55185 - Jönköping/SE
  • 2Department Of Oncology, Karolinska University Hospital, Stockholm/SE
  • 3Department Of Oncology, University Hospital Uppsala Akademiska Sjukhuset, SE-751 85 - Uppsala/SE
  • 4Department Of Oncology, Skåne University Hospital, Lund/SE
  • 5Oncology, Odense University Hospital, 5000 - Odense C/DK
  • 6Department Of Oncology, Linköping University Hospital, Linköping/SE
  • 7Department Of Oncology, Växjö Hospital, Växjö/SE

Abstract

Aim

The value of low-toxic maintenance treatment (mt) strategies after initial induction chemotherapy in metastatic colorectal cancer (mCRC) remains unclear. Mt based on bevacizumab (bev) with or without addition of erlotinib (erlo) have modest effect but to a high expense. Since the efficacy of erlo might be influenced by the KRAS mutational status, this was used as a stratification factor in the present study exploring different mt strategies with bev, erlo and low-dose capecitabine (cap).

Methods

We included pts with mCRC scheduled for first line therapy, ECOG 0-1 and adequate organ and haematological function. Induction treatment with XELOX, XELIRI, FOLFOX or FOLFIRI (investigatoŕs choice) + bev was given for 18 weeks. Pts without progressive disease (PD) were eligible for mt; KRAS wt pts were randomized to mt with bev 7.5mg/kg q3w +/- erlo 150mg qd (arms wt-B vs wt-BE) and KRAS mut pts to bev or metronomic cap 500mg BID (arms mut-B vs mut-C). Mt continued until PD or unacceptable toxicity. Primary endpoint was PFS rate at 3 months after start of mt.

Results

233 pts were enrolled at 11 sites in Sweden and 1 in Denmark between Oct 2010 and May 2012. Median age was 64 years (32-83), 62% male, 68% ECOG 0, 52% had the primary tumour in situ. 138 pts were randomized and started mt; 36 pts in wt-B and wt-BE, respectively and 33 pts in mut-B and mut-C, respectively. The main reasons for non-randomization were PD (n = 30), adverse event (AE) (n = 28) and planned curative treatment (n = 17). PFS rates at 3 months were 65.7% vs 63.6% in wt-B vs wt-BE, p= 1.000; and 74.2% vs 66.7% in mut-B and mut-C, p= 0.582. The frequency of any AE grade 3-4 during induction was 45% and during mt: 28%/58%/18%/15% in wt-B/wt-BE/mut-B/mut-C, respectively.

Conclusions

Addition of erlo to bev as mt in mCRC did not significantly improve PFS ratio at 3 months from start of mt phase in KRAS wt pts, but it did add toxicity. Pooled analysis with KRAS wt pts from the Nordic ACT trial will be performed. The results on metronomic cap as mt warrant further investigation.

Disclosure

A. Johnsson: Honoraria/advisory boards: Genetech, Nordic Drugs, Celgene, Amgen, Bayer. All other authors have declared no conflicts of interest.