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

Date

09 Oct 2016

Session

Basic science and translational research

Presenters

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

Author affiliations

  • 1 Translational Research Laboratory, Institut Català d'Oncologia Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 2 Medical Oncology, Hospital Universitario Virgen del Rocio, Sevilla/ES
  • 3 Medical Oncology, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 4 Medical Oncology, Institut Català d'Oncologia Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 5 Biostatistics For Medical Oncology, Institut Catala de Oncologia, 08907 - Barcelona/ES
  • 6 Pathological Anatomy, Hospital Universitari, Bellvitge/ES
  • 7 Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 8 Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 9 Medical 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
  • 10 Medical Oncology, Hospital de Sant Joan Despí - Moisés Broggi, Hospitalet/ES
  • 11 Medical Oncology, University Hospital del Mar, Barcelona/ES
  • 12 Medical Oncology, Hospital General Universitario de Alicante, 03010 - Alicante/ES
  • 13 Medical Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, Badalona/ES
  • 14 Medical Oncologist, Hospital Universitario Central de Asturias, 33006 - Oviedo/ES
  • 15 Medical Oncology, Hospital Universitario a Coruna - a Corunac, A Coruna/ES
  • 16 Medical Oncology, Institut Català d'Oncologia Hospital Duran i Reynals, Barcelona/ES
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Resources

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.

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