149O - The National University Cancer Institute, Singapore (NCIS) Integrated Molecular Analysis of Cancer (IMAC) precision oncology programme: Frequency o...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Developmental therapeutics
Topics Drug Development
Personalised Medicine
Presenter Nicholas Syn
Citation Annals of Oncology (2016) 27 (suppl_9): ix46-ix51. 10.1093/annonc/mdw579
Authors N. Syn1, V. Heong1, X.W. Lee1, N.S. Sapari2, X.Q. Koh2, Z. Fazreen2, J.S.Y. Lim2, B. Pang3, D. Lim3, A.L. Wong1, R.A. Soo1, W. Yong1, C. Chee1, S. Lee1, B. Goh1, R. Soong2, D.S. Tan1
  • 1Department Of Haematology-oncology, National University Cancer Institute, Singapore, S119228 - Singapore/SG
  • 2Centre For Translational Research And Diagnostics, Cancer Science Institute of Singapore, S117599 - Singapore/SG
  • 3Department Of Pathology, National University Health System, 119074 - Singapore/SG

Abstract

Background

Limited data exists on outcomes of precision oncology studies using multi-marker molecular screening for biomarker-enriched early-phase clinical trials in Asia. The IMAC programme (NCT02078544) is one of the first precision oncology protocols initiated in Asia with the aim of assessing the feasibility and potential value of this approach.

Methods

Tumour samples from pts with advanced/recurrent malignancies referred to the NCIS Developmental Therapeutics Unit (DTU) were prospectively screened for ∼2,800 COSMIC mutations in 50 cancer genes using the Ion AmpliSeqTM Cancer Hotspot Panel v2, and results were used for therapeutic decision-making. Information was collected on reported variants, treatment details and patient outcomes.

Results

From April 28, 2014, to July 18, 2016, IMAC enrolled 192 pts with diverse tumour types, including gynaecological (26%), colorectal (18%), breast (11%) and lung cancers (11%). Next-generation sequencing was feasible in 175 pts (91%), achieving a mean depth of 1,990 reads and uniformity of 96%. Median time between sample receipt to return of results was 36 days (interquartile range [IQR], 21–47). Reportable mutations were found in 142 of 175 pts (81%), and potentially actionable mutations were most frequently reported in TP53 (51% of 142 pts), PIK3CA (23%), KRAS (20%) and PTEN (8%). Ten EGFR-mutant NSCLC pts (7%) received an approved EGFR TKI, and 16 pts (11%) were enrolled into a matched biomarker-enriched clinical trial (PI3K/PTEN/AKT, N = 12; ALK, N = 2; AKT, N = 1; EGFR, N = 1), with the latter pts showing durable clinical benefit (median PFS: 3.7 months, IQR: 1.8–5.5; median OS: 16.4 months, IQR: 6.5–20.3).

Conclusions

Multi-marker molecular screening of cancer pts in the IMAC protocol for therapeutic prioritisation is feasible, shows early evidence of clinical benefit, and is currently supporting a range of ongoing precision oncology studies at our centre. IMAC provides useful data which may aid similar Asian initiatives.

Clinical trial indentification

NCT02078544

Legal entity responsible for the study

Domain Specific Review Board (DSRB), National University Hospital

Funding

National Medical Research Council (NMRC)

Disclosure

All authors have declared no conflicts of interest.