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Value of comprehensive genomic profiling in pre-screening patients for NTRK fusion in STARTRK2 trial: Single centre experience
Ortega-Franco, Ana Adamson-Raieste, A. Rahman, Rozana A Peters, N. Scott, J. A. Aruketty, Sreeja Thomson, C. Dransfield, Sarah Henshaw, A.
Ortega-Franco, Ana
Adamson-Raieste, A.
Rahman, Rozana A
Peters, N.
Scott, J. A.
Aruketty, Sreeja
Thomson, C.
Dransfield, Sarah
Henshaw, A.
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Abstract
Background: Comprehensive genomic profiling (CGP) by next-generation sequencing
(NGS) is increasingly used as a pre-screening tool for clinical trials. The aim of this
project was to retrospectively determine the scope of alterations identified by CGP
that could render patients suitable for alternative early phase clinical trials of
genomically-matched (GM) / immunotherapy (IO) or ‘off-label’ drug use.
Methods: Patients were pre-screened for the STARTRK2 study (Roche sponsored
study of Entrectinib, NCT02568267) at The Christie NHS foundation Trust using
FoundatioCDx. Testing is validated for NTRK, ROS1 and ALK fusion testing but all
pathogenic alterations are reported on a clinical trial specific Foundation Medicine
(FM) report. Results were scrutinised for actionable alterations that could direct
patients to alternative clinical trials or off label drug use.
Results: A total of 269 patients with were consented since FM testing was introduced
in the trial in Jan’2019. FM yielded results in 229 patients (85.2%), mean age was 54,
58.4% were male and 45.8% had 1-2 prior systemic lines. Most prevalent tumour
subtypes were colorectal (26.4%), head and neck (21.6%) and sarcomas (7.1%). Most
prevalent alterations occurred in: TP53 (12.6%), APC (8.4%) and KRAS (4.6%). MSI High was 1.5%. No patients had NTRK/ROS1 fusions, 1 non-small cell lung cancer
patient had ALK fusion. 104 (45.4%) patients were potentially eligible for matched
clinical trials (101 for GM and 3 for IO) and 61 (26.6%) patients could have been
considered for off-label drug use. The most prevalent actionable alterations found
across common and rare disease types were PI3KCA (10%), ERBB2 (6.1%), PTEN
(3.1%), tumour mutation burden 10 mut/Mb (2.6%) and HRAS (1.7%). The following
alterations occurred in <1%: AKT1, KRAS G12C, BRAF V600E, BRCA, FGFR3 and IDH1.
Conclusions: Our results highlight the relevance of CGP in identifying patients for GM
or IO within clinical trials or off-label drug use. The retrospective nature of this work
and the fact that FM results provided within STARTRK2 are not intended for clinical
use precluded implementing these recommendations. NTRK fusions were not
detected in our cohort which highlights the rarity of this event in our population
Description
Date
2021
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Citation
Ortega Franco A, Adamson-Raieste A, Rahman R, Pihlak R, Peters N, Scott J-A, et al. 44P Value of comprehensive genomic profiling in pre-screening patients for NTRK fusion in STARTRK2 trial: Single centre experience [Internet]. Vol. 32, Annals of Oncology. Elsevier BV; 2021. p. S1359.