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Poster display session

3185 - Correlation of circulating tumor DNA (ctDNA) assessment with tissue-based comprehensive genomic profiling (CGP) in metastatic urothelial cancer (mUC)

Date

10 Sep 2017

Session

Poster display session

Presenters

Bradley McGregor

Citation

Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371

Authors

B. McGregor1, S.M. Ali2, P. Grivas3, J.S. Ross4, P.J. Stephens2, V.A. Miller2, B. Forcier2, J. Chung4, S.K. Pal5

Author affiliations

  • 1 Medical Oncology, Dana Farber Cancer Institute, 2115 - Boston/US
  • 2 R & D, Foundation Medicine, 02141 - Cambridge/US
  • 3 Medical Oncology, Cleveland Clinic, 44195 - Cleveland/US
  • 4 Pathology, Foundation Medicine, 02141 - Cambridge/US
  • 5 Medical Oncology, City of Hope, 91010 - Duarte/US
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Resources

Abstract 3185

Background

Tissue-based CGP reveals a multitude of actionable targets in patients (pts) with mUC (Ross et al Cancer 2015). Assessment of ctDNA from blood offers the benefit of avoiding risks of biopsy/surgery and allows for serial assessment.

Methods

In pts with mUC, 50-100 ng of ctDNA was extracted from plasma during routine clinical care. Using adapted sequencing libraries, hybrid capture and sample multiplexed sequencing was performed with an Illumina HiSeq 2500 platform to a median coverage depth of 6353X. This CLIA-certified test of 62 genes detected genomic alterations (GAs) at low allele frequencies (0.1% for substitutions, 1% for indels/rearrangements and 20% for copy number amplification). In several pts CGP data was available from separate tissue-based CLIA-certified tests for which methods have been previously reported (Frampton et al Nat Biotechnol 2013). In addition to examining intra-patient differences, we compared the cumulative frequency of GAs in ctDNA to a large pool of tissue-based CGP in pts with mUC (n = 2024).

Results

27 pts (18:9 M:F) with mUC had ctDNA assessment; median age 68 (range, 52-86). There was evidence for ctDNA in the blood for 25/27 pts (93%), and at least 1 GA was observed in 20/27 (74%) cases. The most frequently altered genes were TP53 (63%), TERT-promoter (33%), PIK3CA (15%), FGFR3 (11%), NF1 (11%) and ERBB2 (7%). With the caveat of a limited sample size, the cumulative frequency of selected clinically relevant GAs was distinct in ctDNA and tissue. The frequency of FGFR3 alteration was lower in ctDNA as compared to tissue (11% vs 23%), as was the frequency of ERBB2 alteration (14% vs 7%). A pt with FGFR3 GA in baseline tumor tissue showed disappearance of FGFR3 GA and evolution of a TP53 alteration in ctDNA following treatment with an FGFR3 inhibitor. In a pt with ERBB2 and TP53 GAs in baseline tumor tissue, ctDNA collected at the time of resistance to cisplatin-based therapy showed persistence of ERBB2 and TP53 GAs and a new NF1 GA.

Conclusions

Using hybrid capture-based genomic profiling of ctDNA, ctDNA was detected in the vast majority of pts with mUC. Utility was demonstrated through detection of potential resistance mutations in pts receiving chemotherapy and targeted agents.

Clinical trial identification

Legal entity responsible for the study

Siraj Ali

Funding

None

Disclosure

B. McGregor: Advisory Board for Enfortumab Vedotin (Seattle Genetics/Astellas Global Pharma) Consultant Lecturer for Bayer Pharmaceuticals. S.M. Ali, J.S. Ross, P.J. Stephens, V.A. Miller, B. Forcier, J. Chung: Employee of and equity interest in foundation medicine inc. P. Grivas: consulting with: Genentech, Bristol-Myers Squibb, Merck & Co., Exelixis, AstraZeneca, ClovisOncology, Bayer, Dendreon, EMD Serono. All other authors have declared no conflicts of interest.

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