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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

3454 - Clinical impact of circulating tumor RAS and BRAF mutation dynamics in metastatic colorectal cancer patients treated with first-line chemotherapy plus anti-EGFR therapy. Combined analysis of two prospective clinical trials

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Cytotoxic Therapy;  Targeted Therapy

Tumour Site

Colon and Rectal Cancer

Presenters

Clara Montagut

Citation

Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281

Authors

C. Montagut1, V. Alonso2, P. Escudero3, C. Fernández-Martos4, A. Salud Salvia5, M. Méndez6, J. Gallego Plazas7, J.R. Rodriguez8, M. Martín-Richard9, J. Fernández-Plana10, J. Aparicio11, J. Feliu Batlle12, X. García de Albéniz13, F. Rojo14, V. Fernández15, B. Claes16, G.G. Maertens16, E. Sablon16, B.A.W. Jacobs17, J. Maurel18

Author affiliations

  • 1 Medical Oncology, Hospital del Mar, 08003 - Barcelona/ES
  • 2 Medical Oncology Service, Hospital Miguel Servet, 50009 - Zaragoza/ES
  • 3 Medical Oncology Service, Hospital Clinico Universitario Lozano Blesa, 50009 - Zaragoza/ES
  • 4 Medical Oncology Service, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 5 Medical Oncology Service, Hospital Arnau de Vilanova, 25198 - Lleida/ES
  • 6 Medical Oncology Service, Hospital de Móstoles, 28935 - Móstoles/ES
  • 7 Medical Oncology Service, Hospital General Universitario de Elche, 3203 - Elche/ES
  • 8 Medical Oncology Service, Hospital Infanta Cristina, Madrid/ES
  • 9 Medical Oncology Service, Hospital de la Santa Creu i Sant Pau, 08041 - Barcelona/ES
  • 10 Medical Oncology Service, Hospital Mútua de Terrasa, 08221 - Terrassa, Barcelona/ES
  • 11 Medical Oncology Service, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 12 Medical Oncology Service, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 13 Ddepartment Of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (MA), US, 02115 - Boston/US
  • 14 Pathology, University Hospital "Fundacion Jimenez Diaz", 28040 - Madrid/ES
  • 15 Dna & Fluis Biobank, Idibaps, 08036 - Barcelona/ES
  • 16 Division Of Clinical Pharmacology, Department Of Medical Oncology, Biocartis, 2800 - Mechelen/BE
  • 17 Division Of Clinical Pharmacology, Department Of Medical Oncology, The Netherlands Cancer Institute, Amsterdam/NL
  • 18 Medical Oncology, Hospital Clínic of Barcelona, 08036 - Barcelona/ES
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Resources

Abstract 3454

Background

To evaluate RAS and BRAF mutation testing in circulating tumor (ct) DNA for prediction of chemotherapy plus anti-EGFR benefit and acquisition of resistance in metastatic colorectal cancer (mCRC) patients (pts).

Methods

RAS and BRAF mutational status, were assessed by Idylla™ system (Biocartis) ctDNA methodology in a baseline plasma sample and a serum sample collected at the time of the last available determination from KRAS exon 2 wild-type (WT) mCRC patients treated with first-line antiEGFR therapy within two first-line prospective biomarker-designed clinical trials (PULSE; NCT01288339 and POSIBA; NCT01276379).

Results

Analysis of extended RAS and BRAF in tissue and plasma from 178 KRAS exon 2 wild-type mCRC pts showed a sensitivity of 59% and a specificity of 90%. Patients with baseline RAS and BRAF (n = 36) mutant ctDNA had a median Progression Free Survival (mPFS) of 8.2 months (CI 95% 6.3-10 months) and 6.7 months (CI 95% 4.3-9.1 months) respectively, whereas double wild-type (2WT) pts had a mPFS of 13.6 months (CI 95% 11.7-15.4 months; p < 0.0001). Analogously the median overall survival (mOS) of baseline RAS and BRAF ctDNA mutant pts was 22.3 months (CI 95% 15.6-29 months) and 8.9 months (CI 95% 6.3-11.4 months) respectively, which were significantly inferior to the mOS of 40.4 months (CI 95% 35.9-44.9 months) in 2WT pts (p < 0.0001). Acquisition of RAS/BRAF mutations was 9/63 (14%) in pts with progressive disease (PD) (i.e, blood draw within 1 month before PD or after PD) (median 24.8 days (-29 to 484 days)) compared to 6/73 (8%) in pts with no PD or blood extraction for ctDNA analysis before 1 month of PD (median -265.6 days (-31 to -1126 days) (p = 0.47). Median OS in patients with RAS/BRAF acquisition was 23.9 months (CI 95% 19.7-27.9 months) compared to 40.6 months (CI 95% NR-NR months) in pts who remained free of mutations (p = 0.016).

Conclusions

Our results confirm that baseline RAS and BRAF testing in ctDNA discriminates PFS and OS. The emergence of RAS/BRAF mutations has limited impact on the time to progression to antiEGFR therapy and confers poor prognosis.

Clinical trial identification

Legal entity responsible for the study

Grupo Español Multidisciplinar de Cáncer Digestivo.

Funding

Biocartis.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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