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Basic science

3936 - Clinical implications of genomic variants identified in over 30,000 advanced-stage cancer patients by next-generation sequencing of circulating tumor DNA

Date

09 Sep 2017

Session

Basic science

Presenters

Sumanta Pal

Citation

Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391

Authors

S.K. Pal1, C. Brooks2, D. Chudova2, J. Odegaard2, D.R. Gandara3, P. Mack4, S. Mortimer2, K. Banks2, R.J. Nagy2, A. Baca2, R. Lanman2, H. Eltoukhy2, A. Talasaz2

Author affiliations

  • 1 Medical Oncology, City of Hope, 91010 - Duarte/US
  • 2 Medical Affairs, Guardant Health, Inc, 94063 - Redwood City/US
  • 3 Thoracic Oncology, UC Davis Comprehensive Cancer Center, 95817 - Sacramento/US
  • 4 Internal Medicine, University of California Davis Cancer Center, 95817 - Sacramento/US
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Abstract 3936

Background

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) enables non-invasive profiling of solid tumor cancers. Over the past few years, research and clinical practice guidelines have highlighted a role for liquid biopsy in patient care; however, few large datasets on clinical use have been published.

Methods

Somatic genomic profiles of 35,492 plasma samples from 30,024 advanced cancer patients were determined by a ctDNA NGS test targeting up to 73 genes (Guardant360®). Accuracy of ctDNA-detected driver alterations (PPV) was assessed by comparing to available matched tissue tests for 646 patients (lung, colon, and other cancer types). A pooled response rate analysis was performed across published/in press datasets presenting response data to alterations detected by Guardant360®.

Results

The full cohort consisted of non-small cell lung cancer (NSCLC) (39%), breast (16%), colorectal (CRC) (10%) and multiple other solid cancer types (35%), with ctDNA alterations detected in 88%, 86%, 88%, and 82%, respectively (86% overall). 19% of patients had 1 or more ctDNA alterations associated with an FDA-approved therapy. Resistance variants were identified in 18% of NSCLC, breast, CRC, prostate, melanoma and GIST patients. PPV ranged from 92-100% for EGFR L858R/E19del/E20ins (98%), ALK/RET/ROS1 fusions (92%), BRAF V600E (95%), KRAS G12/G13/Q61 (94%), and MET E14 skipping mutations (100%). Pooled response rate to 1st line EGFR TKIs (n = 43 NSCLC): 86% [95% CI: 71-94%]; to osimertinib (n = 19 NSCLC): 94% [72-99%]; to rociletinib (n = 63 NSCLC): 54% [41-67%]; to crizotinib (n = 11 NSCLC): 82% [48-97%]; to anti-HER2 agents (n = 7 breast): 86% [49-97%]; (n = 5 gastric): 80% [37-96%].

Conclusions

Use of liquid biopsies is increasing in clinical care, providing an option of obtaining genomic information non-invasively. This dataset, derived from liquid biopsy use in clinical practice, highlights the clinical impact of identifying alterations that are targetable by drugs with regulatory approval, including emergent resistance alterations.

Clinical trial identification

Legal entity responsible for the study

Guardant Health, Inc.

Funding

None

Disclosure

S.K. Pal: Honoraria from Novartis, Medivation, and Astellas Pharma, is a consultant/advisor for Pfizer, Novartis, Aveo, Myriad Pharmaceuticals, Genentech, Exelixis, Bristol-Myers Squibb, Astellas Pharma, and receives research funding from Medivation. C. Brooks, D. Chudova, J. Odegaard, S. Mortimer, K. Banks, R.J. Nagy, A. Baca, R. Lanman, H. Eltoukhy, A. Talasaz: Employee and stockholder of Guardant Health, Inc. P. Mack: Honoraria from Guardant Health, Inc. All other authors have declared no conflicts of interest.

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