Journal article
Velour trial biomarkers update: Impact of RAS, BRAF, and sidedness on aflibercept activity.
- Wirapati, Pratyaksha Swiss Institute of Bioinformatics, Lausanne, Switzerland;
- Pomella, Valentina University of Leuven, Leuven, Belgium;
- Vandenbosch, Ben University of Leuven, Leuven, Belgium;
- Kerr, Peter Almac Diagnostics, Craigavon, Northern Ireland;
- Maiello, Evaristo U.O. Oncologia, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy;
- Jeffery, Grahame Mark Christchurch Hospital, Christchurch, New Zealand;
- Curca, Razvan-Ovidiu D. County Hospital Alba, Alba Iulia Alba, Romania;
- Karthaus, Meinolf Hematology and Onkology, Klinikum Neuperlach, Munich, Germany;
- Bridgewater, John A. University College London Cancer Institute, London, United Kingdom;
- Mihailov, Anca C. University Hospital Cluj, Cluj Napoca, Romania;
- Kiss, Igor Masaryk Memorial Cancer Institute, Brno, Czech Republic;
- Merino, Sandra Hospital Universitari de Sant Joan de Reus, Tarragon, Spain;
- McKendrick, Joseph James Department of Medical Oncology, Eastern Health, Melbourne, Australia;
- Saridaki, Zacharenia Hellenic Group of Young Oncologists (HeGYO), the Hellenic Society of Medical Oncology (HeSMO), Athens, Greece;
- Sagaert, Xavier JA University Hospitals Leuven, Leuven, Belgium;
- Tejpar, Sabine University Hospital Leuven, KUL, Leuven, Belgium;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2017, vol. 35, no. 15_suppl, p. 3538-3538
English
3538 Background: Addition of (ziv)-aflibercept (A) to FOLFIRI in second-line therapy for metastatic colorectal cancer (CRC) has been shown to be beneficial in phase III VELOUR trial (NCT00561470). A follow-up study (NCT01754272) was undertaken to acquire tumor samples for biomarker analyses and identify subgroups of patients with differential treatment effects. The primary results assessing efficacy according to well-established CRC subgroups defined by RAS, BRAF status and sidedness are reported here. Methods: Tissue specimens were collected for 666 patients from 1226 ITT pts. Suitable specimens were assayed for somatic mutation using NGS targeting extended RAS and BRAF genes. NGS assays with no missing values were obtained for 482 pts. Affymetrix gene chip technology was used for whole-transcriptome profiling; sidedness was extracted from available pathological reports. Differences between subgroups were assessed by interaction analysis. Results: The treatment effects on overall survival (OS) for the 482 pts is still significant HR=0.80 (CI 0.65-0.99), and similar to the ITT (n=1226) results (HR=0.82, CI 0.71-0.93). Two established ways of defining mutations (traditional KRAS exon 2 and extended RAS using NGS) show a trend for a differential effect across mutation groups.(see table for OS). Interestingly, BRAF mutants (which are all RAS wild type) show a trend for better outcome Same is seen for PFS and RR. Sidedness did not affect efficacy (HR: 0.83 (0.63- 1.1) for left and HR: 0.83 (0.54-1.3) for right. Conclusions: None of the mutations subgroup results shows significant interaction, although the ratios of treatment HR favor RAS wild types. Similar trends were observed in published trials with bevacizumab or ramucirumab. Sanofi supported this ISS. Clinical trial information: NCT01754272. [Table: see text]
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1200/jco.2017.35.15_suppl.3538
- ISSN 0732-183X
- Persistent URL
- https://sonar.ch/global/documents/63147
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