Found 2 Presentations For Request "102P"
1102P - Efficacy endpoints studied in clinical trials for early-onset leukaemia (ID 2914)
- Dylan Said (Msida, Malta)
Acute lymphoblastic leukaemia (ALL) is associated with high survival rates in paediatrics and young adults and less favourable outcomes in older adults. Clinical trials (CTs) studying survival-based endpoints in ALL lead to significantly prolonged trial durations, resulting in delays to medicines access. Biomarkers in ALL have been correlated with longer-term outcomes, potentially accelerating the clinical development of novel treatments. The aim of this study was to characterise efficacy measures investigated in ALL CTs conducted in the European Union (EU)/Economic Area (EEA).
Interventional Phase II to Phase IV ALL CTs registered in the EU Clinical Trials Register over an 11-year period (2007-2017) were identified. Therapeutic CTs reporting efficacy data in the English language for investigational medicinal products of chemical, biological and biotechnological origin were included in the study. A protocol design or age filter was not applied to avoid limiting the scope of outcomes identified. Primary and secondary efficacy endpoints were extracted from the selected CTs and categorised according to type of measurement. A data mining process was performed to detect trends in outcomes studied.
The data set comprised 68 CTs representing about 20,000 patients. The majority of trials (69%, n = 47) recruited patients from the adult population (18-64 years) and conducted only Phase II studies (62%, n = 42). Twenty-three unique efficacy endpoints were identified and stratified into the clusters of survival (n = 4), time-to-event (n = 3), response rates and biomarkers (n = 11) and other (n = 5). Fifty-three per cent (n = 36) of the trials reported 4-10 outcomes, with a mean of 4 outcomes per CT (range 1-10). The principal endpoints evaluated in CTs consisted of overall survival (CTs: 63%, n = 43), minimal residual disease (CTs: 50%, n = 34), event-free survival (CTs: 40%, n = 27) and disease-free survival (CTs: 40%, n = 27).
The high uptake of minimal residual disease as an efficacy parameter in ALL CTs is in line with reported findings confirming the prognostic value of this marker on clinical outcomes. Heterogeneity in the selection of efficacy endpoints was observed which warrants future work on the standardisation of efficacy outcomes in ALL CTs.
The Malta Medicines Authority. The Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta.
Legal entity responsible for the study
Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta.
Government of Malta, Endeavour Scholarship Scheme 2017.
All authors have declared no conflicts of interest.
102P - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients (ID 5366)
- Xiaolong Jiao (Whippany, United States of America)
Larotrectinib is the first therapy approved in the U.S. for locally advanced or metastatic solid tumors with neurotropic tyrosine receptor kinase (NTRK) gene fusions. NTRK gene fusions have been documented with variable frequency across numerous tumor types; limited data exist regarding the relationship of NTRK gene fusions with other targetable biomarkers. This study evaluated the co-occurrence of NTRK gene fusions with other therapy molecular markers in cancer patients.
This retrospective study included cancer patients from a de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB) who had next-generation sequencing (NGS) between Jan 2011 and July 2018. The co-occurrence frequencies of NTRK gene fusions with the following markers was determined using NGS assays including FoundationOne and FoundationOne Heme: tumor mutation burden (TMB), microsatellite instability (MSI), ALK, BRAF, ERBB2, EGFR, ROS1, and KRAS.
An evaluable sample of 15,971 of 33,398 patients in the CGDB had one of 18 histologies where at least one NTRK fusion patient was identified. NTRK gene fusions were identified in 29 patients: 55% (16/29) were female; 69% (20/29) were Caucasians. The median age was 60 years (Q1-Q3: 49.0-65.0). Fifteen different fusion partners were identified; the most frequent were ETV6-NTRK3 (n = 8), TPM3-NTRK1 (n = 6), and TPR-NTRK1 (n = 3). Co-occurring genomic alterations are shown in the table. Variants of “known” or “likely” functional status were included MSI status missing for 12 patients
Co-occurring biomarkers Patients with NTRK gene fusions (N = 29), % (n) TMB High (>20 mut/mB) TMB Medium (<20, >5 mut/mB) 20.7 (6/29) 10.3 (3/29) MSI (high) 17.6 (3/17) ALK rearrangement 0.0 (0/29) BRAF alteration 3.5 (1/29) ERBB2 amplification 0.0 (0/29) EGFR alteration 3.5 (1/29) ROS1 alteration 0.0 (0/29) KRAS alteration 10.3 (3/29)
Variants of “known” or “likely” functional status were included
MSI status missing for 12 patients
The study confirmed the rarity of NTRK gene fusions in cancer patients. Co-occurrence of the biomarkers ALK, BRAF, ERBB2, EGFR, ROS1, or KRAS was uncommon. These results highlight the importance of identifying patients with NTRK gene fusion-driven cancers, through molecular testing, who will benefit from the use of selective TRK kinase inhibitors across different solid tumors.
Michael Sheldon, PhD, of Scion, London, UK, funded by Bayer.
Legal entity responsible for the study
X. Jiao: Full / Part-time employment: Bayer. A. Lokker: Full / Part-time employment: Flatiron Health; Shareholder / Stockholder / Stock options: CVS Health, Roche, Medtronic, Sangamo Therapeutics. J. Snider: Full / Part-time employment: Flatiron Health; Shareholder / Stockholder / Stock options: Roche. E. Castellanos: Full / Part-time employment: Flatiron Health. S. Nanda: Full / Part-time employment: Bayer. V. Fisher: Full / Part-time employment: Foundation Medicine. J. Zong: Full / Part-time employment: Bayer. K. Keating: Full / Part-time employment: Bayer. M. Fellous: Full / Part-time employment: Bayer.