Data Insights

ASCO Publications 2020

Stability of rare TP53 co-mutations in AML patients

Acute Myeloid Leukemia (AML) is a devastating disease with poor overall survival. Access to precision medicines, is revolutionizing AML care and is driving an increase in Next Generation Sequencing (NGS) utilization to determine the genomic profile of patients with AML. Advanced analysis into the interplay between mutational status for multiple genes is granting access to new targeted and precision medicine treatment options with improved outcomes.

Acute myeloid leukemia (AML) is a hematologic neoplasm with poor 5-year survival (33%; US 2016), a median survival of only 4 months for relapsed/refractory cases, and in 2016, a US incidence of 19,950 cases and 10,340 deaths. With the largest patient cohort over 65, AML treatment costs in the first year are > $25,000 per patient per month (PPPM); the initial month’s cost is $82,328. Mutations in the FMS-like tyrosine kinase 3 (FLT3+) pathway confer resistance to standard chemotherapy and reduce the likelihood of survival after relapse. In 2017 and 2018, the FDA approved midostaurin and gilteritinib, two current FLT3+ precision medicines for AML. Here, we determine the economic burden of not testing for FLT3+.

KRAS G12C is a distinctively aggressive, poor survival, tumor genotype conferring resistance to anti-EGFR therapies in lung, colorectal (CRC) and pancreatic cancers. Prospective therapies targeting G12C have demonstrated promising activity in Phase I trials. In the advent of potentially transformative novel inhibitor therapies, we assess the need for earlier and repeated tumor profiling between treatments to accurately guide further therapeutics and assess market readiness for specified testing.

The development and launch of first-generation tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib and entrectinib, has brought targeted treatment options to neurotrophic tropomyosin-related kinase (NTRK) fusion–positive adult and pediatric cancer patients who may have been out of treatment options. Widespread adoption of NTRK fusion testing is needed to support successful selection of patients for these TRK inhibitors as well as other targeted therapies. The objective of this study was to investigate global availability of NTRK fusion testing, with a specific focus on Asia.

Homologous Recombination Repair (HRR) gene mutations result in Homologous Recombination Deficiency (HRD) associated with increased risk of high grade serous ovarian (HGOC) cancer and subsequent response to PARP inhibitors (PARPi). Traditionally, HRD has been determined by testing for germline and/or somatic BRCA1/2 mutations. Today, a growing number of HRR gene mutations are known to result in HRD and genomic instability, thus being a suitable target for PARPi. Therapy response to PARPi is highest in BRCA-mutant followed by HRD+/non-BRCA-mutant HGOC. Today, no standard HRD testing methods exist, causing confusion for physicians, and leading to poor outcomes for missed PARPi eligible patients. Thus, there is need to understand HRD testing utilization and methods in HGOC to inform best practices and optimize HRD testing in the clinic.