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Poster Display session 2

4481 - Undetectable RAS mutant clones in plasma: possible implication for therapy and prognosis in the patient with RAS mutant metastatic colorectal cancer?

Date

29 Sep 2019

Session

Poster Display session 2

Presenters

Mohamed Bouchahda

Citation

Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246

Authors

M. Bouchahda1, A. Karaboué2, R. SAFFROY3, J. HAMELIN3, N. BOSSELUT3, A. LEMOINE3

Author affiliations

  • 1 Medical Oncology Department, Paul Brousse Hospital - Villejuif ; Clinique Saint Jean L Ermitage - Melun; Clinique du Mousseau - Evry; INSERM UMR 935 Villejuif., 94800 - Villejuif/FR
  • 2 93, Centre hospitalier intercommunal Le Raincy-Montfermeil, 93370 - Montfermeil/FR
  • 3 Department Of Biochemistry, Paul Brousse hospital, 94800 - Villejuif/FR
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Resources

Abstract 4481

Background

Combining Cetuximab with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with RAS wild type (RAS-wt) locally advanced or metastatic colorectal cancer (mCRC). Therefore, this active treatment excludes 60% of patients (pts) with muted primary tumor. We tested in this pilot study Cetuximab-based therapy in pts with RAS-wt in plasma whose primaries were RAS muted (RAS-mt).

Methods

We analysed KRAS, NRAS, BRAF and PI3KCA mutations in plasma using a new and ultra-sensitive analysis based on mass spectrometry detection (MassARRAY System with Ultra SEEK technology; detection of 0.1% muted alleles) in pts with histological confirmed RAS-mt mCRC after consent. Pts with plasma RAS-wt whose diseases were progressive received Cetuximab-FOLFIRI while plasma RAS-mt pts received investigator’s proposal therapies.

Results

Sixteen pts were registered in three centers. There were 11 males (69%) and 5 females (31%) aged 48 to 81 years (median, 69) with unresectable metastatic adenocarcinoma from colon cancer (9 pts, 56%) and rectum cancer (7 pts, 44%). They had a median of 2 metastatic sites (1 to 4) and had previously received 1 to 4 chemotherapy lines (median, 3). Plasma genotyping showed RAS-mt in 7 patients (44%) and RAS-wt in 9 patients (56%). The 9 pts with plasma RAS-wt received 1 to 16 courses of Cetuximab-FOLFIRI (median, 6). We observed as best response, 1 complete response, 3 partial responses, and 1 progressive disease. Three pts were not assessed yet for efficacy. No grade 3-4 toxicity was encountered. At the cut-off time on 2019.04.23, median follow-up was 5.3 months (0.3 to 19.5). Survival rate were 77.8% (7/9) and 28.6% (2/7) for pts with RAS-wt and RAS-mt respectively. Median overall survival was not reached for pts with RAS-wt whereas it was 4.7 months [95%CL, 0.0-9.6] for RAS-mt pts, p (Log Rank)=0.001.

Conclusions

Our finding suggests that pts with RAS-mt mCRC whose plasma biopsies are RAS-wt could benefit from cetuximab-based therapy. As a result to these preliminary data, we have planned a phase II study targeting the plasma RAS-wt with EGFR inhibitors in first line mCRC.

Clinical trial identification

Editorial acknowledgement

AK-SCIENCE, Vitry-Sur-Seine, France.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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