Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display

3764 - The use of next generation sequencing (NGS) to guide patient selection for phase 1 clinical trials

Date

10 Oct 2016

Session

Poster display

Presenters

Rowan Miller

Citation

Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368

Authors

R.E. Miller1, N.F. Brown1, A. Speirs2, H.M. Shaw1, S. Adeleke2, P. Gougis1, P. Bennett3, T. Meyer4, C. Swanton5, M. Forster4, R.S. Kristeleit4

Author affiliations

  • 1 Uclh/nihr Clinical Research Facility, University College London Hospital, W1T 7HA - London/GB
  • 2 Medical Oncology, UCL - University College London, WC1E 6BT - London/GB
  • 3 Sarah Cannon-ucl Laboratories, UCL- Advanced Diagnostics Molecular Profiling Laboratory,, WC1E 6JA - London/GB
  • 4 Medical Oncology, University College London Cancer Institute, WC1E 6DD - London/GB
  • 5 The Francis Crick Institute, UCL - University College London, London/GB
More

Resources

Abstract 3764

Background

Therapeutically targeting actionable mutations in cancer may increase response rates in Phase I clinical trials. We undertook a pilot study to assess the feasibility and therapeutic benefit of incorporating NGS screening into the patient pathway for phase 1 cancer trials.

Methods

NGS tumour profiling was performed using a 22 gene amplicon-based panel (Life Technologies Colon & Lung V2) on 117 consecutive patients (pts) referred over a 13 month period for Phase I trials. BRCA1/2 analysis was performed in pts with epithelial ovarian cancer.

Results

117 pts (67% female) with a median age of 59 (range 22-78) years were included. Common tumour types were ovarian (n = 20), colorectal (n = 16), breast (n = 13), endometrial (n = 12) and lung (n = 8) cancer. NGS was successfully performed in 108 (92%) pts with a median time to results of 12 days (range 6-39). 82% of pts (89/108) had a detected variant in ≥ 1 gene with an average of 3 variants (range 0-26) in 2 genes (0-10) per case. Common mutations included TP53 (69%), KRAS (14%), PIK3CA (11%) and SMAD4 (9%). BRCA1/2 mutations were present in 11 (55%) ovarian cancer pts. Overall, 49 (45%) pts had ≥ 1 actionable mutation. Detected variants were reviewed in a local genomics review board to assess actionability prior to considering therapy. 53 pts were commenced on a Phase I trial; 18 (34%) were genotype directed. Median duration on trial was 73 days for pts on genotype (7-260 days) or non-genotype (20-582) directed trials with 50% and 24% of allocated patients continuing on study respectively. Of pts evaluable for response (n = 47), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 50%, 29% and 21% of pts on genotype directed trials and 20%, 37% and 43% of pts on non-genotype directed respectively. Excluding pts on BRCA1/2 directed trials, PR, SD and PD were observed in 33%, 33% and 33% of pts respectively in genotype-directed studies.

Conclusions

NGS is feasible in real time and may affect clinical outcome in the phase 1 setting. Almost half of pts had a potentially actionable mutation. Initial response rates for pts treated on genotype-driven trials are encouraging. Benefit is likely to be augmented using a broader NGS panel which is planned for future assessment.

Clinical trial identification

Legal entity responsible for the study

UCLH/NIHR Clinical Research Facility

Funding

UCLH/NIHR Clinical Research Facility

Disclosure

P. Bennett: Employee of UCL- Advanced Diagnostics Molecular Profiling Laboratory, Sarah Cannon-UCL Laboratories. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings