In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e14108-e14108
Abstract:
e14108 Background: Biopsy-driven clinical trials are essential to develop personalized therapeutics, since many critical questions are best addressed in the tumor tissue being treated. In the metastatic setting, intrinsic resistance occurs even with the most advanced therapeutic agents, and even in responders, acquired resistance is inevitable. We have designed a prospective study to identify biomarkers of clinical resistance to standard first-line therapy (FOLFOX, XELOX or FOLFIRI in combination with bevacizumab in patients with metastatic CRC (NCT00984048). Methods: Eligible patients have confirmed metastatic CRC, measurable disease, and consent to three needle-core biopsies (NCBs) of a non-resectable liver metastasis before treatment and at resistance. This study is approved at several Quebec hospitals, demonstrating that Research Ethics Boards recognize the value of biopsy-driven studies without therapeutic benefit. Results: Forty patients agreed to partake in this multi-center trial and to provide NCBs. Of these, 5% were non-neoplastic, and 5% had neuroendocrine origins. Using standard operating procedures developed for this trial, we were able to both preserve morphology and obtain high-quality genomic material. We demonstrate that this material is suitable for DNA analysis (array comparative genomic, methylation profiling) and RNA analysis (gene expression profiling, splicing isoforms variants and micro RNA profiling). In parallel, we have generated resistant CRC cell lines resistant to the combination therapy to further study biomarkers of resistance. Challenges in obtaining a biopsy at time of progression include death, patient refusal, heterogeneity of tumors, metastasis at a different organ site, and time constraints for re-biopsy. No significant adverse events were reported related to the biopsy procedure. Conclusions: We conclude that obtaining serial liver NCBs are challenging, but safe and feasible in metastatic CRC patients with unresectable liver disease. This study will provide insight on the relevance of metastatic tissue in assessing signatures of clinical resistance.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e14108
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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