56PD - Extended genotyping of RAS/BRAF for improved selection of metastatic CRC patients to anti-EGFR therapy: Comparison of three platforms

Date 09 October 2016
Event ESMO 2016 Congress
Session Basic science and translational research
Topics Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Daniel Azuara
Citation Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363
Authors D. Azuara1, R. Garcia-Carbonero2, P. García Alfonso3, C. Santos-Vivas4, V. Navarro5, M. Varela6, A. Carrato7, E. Elez8, M.T. Cano9, F. Losa10, C. Montagut11, B. Massuti Sureda12, J.L. Manzano13, J. Vieitez14, M. Valladares-Ayerbes15, X. Sanjuan6, G. Capellá1, J. Tabernero8, E. Aranda9, R. Salazar16
  • 1Translational Research Laboratory, Institut Català d'Oncologia Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 2Medical Oncology, Hospital Universitario Virgen del Rocio, Sevilla/ES
  • 3Medical Oncology, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 4Medical Oncology, Institut Català d'Oncologia Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 5Biostatistics For Medical Oncology, Institut Catala de Oncologia, 08907 - Barcelona/ES
  • 6Pathological Anatomy, Hospital Universitari, Bellvitge/ES
  • 7Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 8Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 9Medical Oncology, Reina Sofía Hospital, University of Córdoba, Maimonides Institute of Biomedical Research (IMIBIC). Spanish Cancer Network (RTICC), Instituto de Salud Carlos III,, 14004 - Cordoba/ES
  • 10Medical Oncology, Hospital de Sant Joan Despí - Moisés Broggi, Hospitalet/ES
  • 11Medical Oncology, University Hospital del Mar, Barcelona/ES
  • 12Medical Oncology, Hospital General Universitario de Alicante, 03010 - Alicante/ES
  • 13Medical Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, Badalona/ES
  • 14Medical Oncologist, Hospital Universitario Central de Asturias, 33006 - Oviedo/ES
  • 15Medical Oncology, Hospital Universitario a Coruna - a Corunac, A Coruna/ES
  • 16Medical Oncology, Institut Català d'Oncologia Hospital Duran i Reynals, Barcelona/ES

Abstract

Background

The significance of low-frequent RAS pathway mutated alleles and the optimal sensitivity cut-off in the prediction of response to anti-EGFR therapy in metastatic colorectal cancer (mCRC) patients remains controversial. We aimed to evaluate the added value of RAS panel using two commercial assays (Roche Cobas® and Qiagen Therascreen® pyrosequencing kit) and a highly-sensitive and quantitative digital PCR (dPCR).

Methods

Analysis of hotspots including RAS (KRAS/NRAS ex 2/3/4) and BRAF (ex 15) was analyzed in tumor FFPE samples from 585 mCRC patients treated with anti-EGFR (n = 252) or bevacizumab (n = 333) from trials and retrospective series from the TTD/RTICC Spanish network. Response rate (RR), progression-free survival (PFS) and overall survival (OS) were correlated to the mutational status and the mutated allele fraction.

Results

In patients treated with anti-EGFR 33% and 36% were positive for one mutation with the Cobas® and Therascreen® assays respectively. Analysis by dPCR increased to 45%. An inverse correlation between the fraction of mutated alleles and radiological response was observed (p 

Conclusions

RAS and BRAF mutational analysis improved prediction of response to anti-EGFR therapy. Additionally, dPCR with a threshold of 1% outperformed the other platforms in first-line setting.

Clinical trial identification

Legal entity responsible for the study

Spanish Cooperative Group for Digestive Tumour Therapy

Funding

F. Hoffmann-La Roche LTD

Disclosure

P. García Alfonso: Advisory role: Roche, Merck, Amgen, Sanofi, Lilly and Bayer. M. Valladares-Ayerbes: Consultant or advisory role: Amgen. Honoraria: Roche, Merck, Sanofi. E. Aranda: Advisory role from Amgen, Bayer, Celgene, Merck, Roche and Sanofi. R. Salazar: Research funding: Roche Pharma, Roche Diagnostics. All other authors have declared no conflicts of interest.