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Poster Display session 2

5285 - RAS mutant allele fraction in plasma predicts benefit to anti-angiogenic based first line treatment in metastatic colorectal cancer


29 Sep 2019


Poster Display session 2


Tumour Site

Colon and Rectal Cancer


Giulia Martini


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


G. Martini1, E. Elez2, F.M. Mancuso3, M.A. Gomez España4, G. Caratù3, J. Matito3, G. Argiles Martinez2, N. Mulet Margalef5, M.J. Ortiz Morales4, F.J. Ros Montana2, A. Garcia1, R. Comas1, C. Santos Vivas6, R. Perez-Lopez1, P.G. Nuciforo7, O. Casanovas8, R. Dienstmann9, J. Tabernero10, E. Aranda Aguilar11, A. Vivancos3

Author affiliations

  • 1 Oncology Dept., Vall d’Hebron Institute of Oncology (VHIO),, 08035 - Barcelona/ES
  • 2 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 3 Cancer Genomics, Vall d'Hebron Institute of Oncology (VHIO)-Cellex Center, 08035 - Barcelona/ES
  • 4 Medical Oncology, University Hospital Reina Sofia, IMIBIC, 14004 - Cordoba/ES
  • 5 Medical Oncology, Institut Català d'Oncologia Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 6 Oncology Department, Catalan Institute of Oncology. Hospital Druan y Reynals, 08908 - Barcelona/ES
  • 7 Molecular Oncology Dept., Vall d'Hebron Institute of Oncology (VHIO)-Cellex Center, 08035 - Barcelona/ES
  • 8 Oncology Dept., Institut Català d'Oncologia Hospital Duran i Reynals, 8907 - Barcelona/ES
  • 9 Oncology Data Science (odyssey) Group, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 10 Oncology, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), 08001 - Barcelona/ES
  • 11 Department Of Medical Oncology, University Hospital Reina Sofia, 14004 - Cordoba/ES


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Abstract 5285


So far, no biomarkers of response to anti-angiogenic drugs are available in colorectal cancer (CRC) treatment. Liquid biopsy technique identifies actionable targets in CRC patients (pts), tracking dynamic mutational changes. We and others described RAS mutant allele fraction in plasma (plMAF) as an independent prognostic marker in metastatic CRC (mCRC). Here, we explored the predictive value of plMAF in RAS mutant pts treated in first line with chemotherapy +/- bevacizumab (bev).


A multicentric prospective/retrospective analysis was conducted. We collected data from 226 mCRC pts and selected the subset not eligible for metastasis resection that had basal plMAF sample evaluable for RAS mutant MAF quantification using digital PCR (BEAMing). Pts were stratified as high (≥ 5.8%) or low (< 5.8%) plMAF based on previously defined cut-off (Sanz-Garcia E, ESMO GI, 2017). We investigated associations between different clinicopathological variables (gender, n° and site of metastases, CEA levels, primary site location) and progression-free survival (PFS) stratified by plMAF RAS levels using Cox regression models and survival data were calculated by the Kaplan-Meier method.


From October 2017 to May 2019, BEAMing analysis from 62 basal plasma samples was performed. 42 pts (67.7%) were classified as high and 20 pts (32,3%) as low plMAF. Among high RAS plMAF, 24 pts received FOLFOX+bev (57%) and 20 pts FOLFOX alone (43%). In this high plMAF subgroup, a statistically significant longer PFS favouring FOLFOX+bev was observed when compared to FOLFOX alone (10.7 versus 6.9 months, respectively; HR: 0.30; p = 0.002). In the low RAS plMAF subgroup, no differences in terms of PFS were observed in either arm (8.9 versus 8.7 months, respectively; HR: 0.70; p = 0.6). Multivariate PFS model showed no association between RAS plMAF and clinicopathological variables, except for high RAS plMAF and treatment benefit with FOLFOX+bev.


Our results indicate that tumor-borne RAS plMAFs may constitute a potential predictive biomarker of efficacy for anti-angiogenic agents in mCRC. Confirmatory studies in randomized cohorts will be performed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

VHIO (Vall d’Hebron Institute of Oncology).


AECC (Asociación Española Contra el Cáncer).


G. Martini: Research grant / Funding (self), Research Project supported by ESMO with the aid of a grant from Amgen: ESMO-AMGEN. E. Elez: Honoraria (self): Merck Serono; Honoraria (self): Sanofi; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Servier; Honoraria (self): Amgen; Honoraria (self): Array. G. Argiles Martinez: Honoraria (self), Honoraria (institution), Research grant / Funding (self), Travel / Accommodation / Expenses: Hoffmann-LaRoche, Bristol-Myers Squibb, Bayer, Servier, Amgen, Merck Serono, Menarini; Honoraria (self): Menarini; Honoraria (institution): Boston Pharmaceuticals; Honoraria (institution): Genentech; Honoraria (institution): Boehringer Ingelheim. M.J. Ortiz Morales: Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert Testimony: Sanofi. P.G. Nuciforo: Honoraria (self): BAYER; Honoraria (self): MSD; Honoraria (self): Novartis. R. Dienstmann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Symphogen, Ipsen, Amgen, Sanofi, MSD, Servier; Research grant / Funding (self): MERCK. J. Tabernero: Advisory / Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Part. E. Aranda Aguilar: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi. A. Vivancos: Advisory / Consultancy: sysmex; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck; Advisory / Consultancy: Bristol-Meyers Squidd; Advisory / Consultancy: Guardant Health. All other authors have declared no conflicts of interest.

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