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Biomedical subjects

Shi-Yi Wang

Publications and source records attributed to Shi-Yi Wang.

3 recordsLinked to original sources

Matched targeted therapy use after broad genomic profiling in advanced Non-Small cell lung cancer.

INTRODUCTION: While broad genomic profiling is increasingly used in advanced NSCLC (aNSCLC), the impact of test results on subsequent guideline-concordant targeted therapy selection remains incompletely understood. METHODS: Using a merged dataset of two large, nationwide, patient-level databases, we identified patients who were diagnosed with aNSCLC 2017-2023, had potentially actionable genomic profiling findings, and initiated systemic therapy. Patients were categorized into actionability subgroups based on contemporaneous regulatory approvals and NCCN guideline recommendations. Within each subgroup, we assessed receipt of guideline-concordant targeted therapy within 24 months, including potential underuse (non-receipt of recommended treatment) and overuse (receipt of non-recommended treatment). RESULTS: Among 6620 patients (67.4% ≥65 years, 54.6% female, 68.9% White), guideline-concordant targeted therapy use varied substantially by actionability category: 2313 (89.6%) of 2582 patients with available 1st-line on-label options received them (10.4% underuse), while 212 (67.3%) of 315 patients with available later-line on-label options received them after 1st-line (32.7% underuse). Among 441 patients with available guideline-concordant off-label options, only 122 (27.7%) received them (72.3% underuse). Conversely, 238 (8.6%) of 3282 patients received matched but guideline-discordant off-label options, representing overuse of ineffective or unestablished therapies. Smoking history, squamous histology, and high PD-L1 expression were associated with lower targeted therapy receipt. CONCLUSIONS: In this cohort study of aNSCLC care, the guideline concordance of targeted therapy use varied by clinical actionability of molecular testing results. Underuse was more common in patients with later-line and off-label targeted therapy options. Patients with classical smoking-related risk profiles were substantially less likely to receive targeted therapy even when actionable alterations were identified.

Journal Article

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

CART

Molecular Biomarker Testing Patterns and Turnaround Time in US Patients With Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Patients with advanced non-small cell lung cancer (aNSCLC) are recommended to undergo molecular testing for targetable genomic alterations. However, as high-throughput methods are increasingly used, long test turnaround time (TAT) may lead to lower receipt of appropriate targeted therapy. Guidelines recommend a 2-week TAT for ALK and EGFR testing, 2 prevalent pathogenic alterations with highly effective targeted therapies. PATIENTS AND METHODS: Using an electronic health record-derived, deidentified database, we conducted a retrospective cohort study of patients with aNSCLC diagnosed between 2011 and 2023 who received testing for ≥1 of 8 molecular markers. We assessed the number of biomarkers tested per patient, testing modality, and TAT (defined as the interval between specimen collection and result date) over time. We also evaluated patients with ALK/EGFR-altered aNSCLC who initiated early nontargeted treatment prior to test result availability, examining associations with TAT and clinical outcomes. RESULTS: The study sample comprised 33,945 patients, with a mean age of 68.2 years; 49.4% were female, 58.3% were White, and 83.4% reported a history of smoking. From 2011 to 2023, the mean number of biomarkers tested per patient (range, 2.0-6.8) and the use of next-generation sequencing (NGS) increased, whereas the mean TAT converged to 3 weeks. Fewer than half of the patients with ALK/EGFR-altered aNSCLC had a TAT of ≤2 weeks, and 1 in 8 initiated early nontargeted treatment. Longer TAT was associated with early nontargeted treatment when analyzed as both a continuous variable (odds ratio, 1.83 per week) and a binary variable (TAT >2 vs ≤2 weeks; odds ratio, 6.02). Early treatment was associated with worse median progression-free survival (9 vs 11 months) in patients with ALK/EGFR-altered aNSCLC. CONCLUSIONS: Biomarker testing and NGS use have increased over time in US patients with aNSCLC. TAT has plateaued and remains longer than recommended in consensus guidelines. Longer TAT was associated with early nontargeted therapy in patients with ALK+/EGFR+ aNSCLC, leading to suboptimal first-line treatment and poorer clinical outcomes.

Humans