NTRK positivity and conversion to appropriate personalized treatment.

Abstract

e15163 Background: The field of precision medicine continues to grow in size and complexity. In oncology alone, the FDA has approved companion diagnostics for 53 unique biomarkers across 28 different indications linking to 59 separate drugs to treat cancer patients beyond traditional options (FDA 21 December 2023). Two of these drugs, entrectinib and larotrectinib, are approved across all tumor types for NTRK fusions, which while rare in common cancer indications are more common in understudied, rare cancers (Cocco et al Nature 2018). These treatment options have significant outcomes for patients, however, there is still a large barrier for patients to access the right treatment (Sadik et al JCO 2022). We hypothesized not all patients with identified NTRK alterations are being prescribed these treatments and assessed this in real-world data for US oncology patients. Methods: Diaceutics proprietary DXRX database contains real-world claims, specialty pharmacy and laboratory data that enables the identification of patients positive for biomarker alterations and resultant treatment pathways in the US. The result-level laboratory data was filtered to solid tumor patients who were positive for NTRK alterations in the 2-year window between 2022 and 2023. The identified NTRK positive patients were then tokenized and joined to our medical claims and pharmacy data to assess which treatment combinations these patients received. Results: A total of 4,251 cancer patients were identified as having tumors with NTRK alterations. Of the patients that could be linked to treatment (800 patients), 1.5% (n = 12) patients went on to receive a targeted treatment for their NTRK alteration, either entrectinib (n = 8), larotrectinib (n = 3), or both entrectinib and larotrectinib (n = 1). When not prescribed either of these, 43.25% (n = 346) patients received different targeted treatment, possibly because of other alterations identified. There were still 55.25% (n = 442) receiving no targeted treatment, either being prescribed chemotherapy (chemo) alone (28.25%, n = 226), immunotherapy (IO) alone (21.1%, n = 169), or an IO/chemo combination (5.9%, n = 47). Conclusions: Despite the established significant disease control from targeted NTRK treatments, most patients with these alterationsdo not have an opportunity to benefit from the most effective personalized treatment for their cancer. These findings may suggest that targeted therapy for rarer and/or tissue agnostic alterations may get deprioritized or overlooked. Therefore, we advocate that a new, different approach for bringing targeted treatments for rare biomarkers to patients is still needed. Different economic models and an optimized approach to engage and inform key stakeholders including oncologists of the presence and benefit of targeted treatments is critical and needs further investigation.