Abstract PS2-09-28: Use of DiviTum®TKa assay to assess CDK4/6 inhibitor medication compliance and drug interactions

Abstract Background: CDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) are 1st line treatment for metastatic hormone positive breast cancer (ER+mBC). CDK4/6is have several known drug interactions (i.e. with CYP3A inducers) leading to decreased serum concentrations and potentially shorter progression free survival (PFS). The DiviTum ® TKa assay by Biovica was designed to measure thymidine kinase, a marker of cell proliferation, and FDA approved in 2022 as a prognostic marker in ER+mBC. TKa suppression by CDK4/6is is associated with prolonged PFS. We assessed if TKa values at C1D15 could identify low compliance or drug interactions leading to sub-optimal TKa suppression and if counseling and adjusting concurrent medications could restore TKa suppression. Methods: This is a single institution pilot study of patients with ER+mBC treated with 1st line CDK4/6i+ET. Serum samples from routine blood draws were sent to CLIA-certified Biovica lab. Participants with sustained TKa levels (100 DuA) at C1D15 were assessed for medication compliance and drug interactions using Morisky Adherence Scale and chart review of all medications. TKa levels were then repeated at subsequent standard blood draws. Results: 30 patients enrolled 1/2024 - 5/2025, median age 64, all female, 77% white, 57% on ribociclib, 77% without visceral metastases. All participants had at least 3 consecutive TKa levels. Prior to treatment TKa results were available for 11 participants, among these median DuA was 228, 5 had 100 DuA. 15/16 participants had suppressed (100 DuA) levels by C1D15. 25/30 participants (83.3%) had suppressed levels by C2D28. Only one participant had consistently elevated TKa levels 2000 on therapy and had progression of disease (POD) in 2 mo. 3 participants had initial decrease in TKa levels followed by subsequent rise. One participant was mistakenly taking abemaciclib qdaily and after correcting to bid her TKa levels decreased. Another participant was briefly on amoxicillin-clavulanate for sore throat and TKa levels decreased after antibiotic completion. The third participant could not tolerate ribociclib due to fatigue and TKa levels were elevated during treatment hold, then decreased when she was switched to palbociclib. One participant continued to have sustained TKa levels on CDK4/6i after an initial decrease, no medication adherence or drug interactions were identified, and she had POD within 3 months. All participants with suppressed TKa levels (25/30) remain on treatment with stable disease at median follow up of 8 mo. Conclusions: The Divitum ® TKa assay can be a useful tool in monitoring adherence and drug interactions in the clinic that could be addressed with counseling and concomitant medication review. Persistently elevated TKa levels early on-treatment predict short PFS, whereas suppression of TKa levels is associated with prolonged PFS. Citation Format: M. Rozenblit, A. Kahn, N. Wiesendanger, S. Schellhorn, N. Fischbach, D. Boyd, M. DiGiovanna, K. Fenn, W. Kidwai, K. Sabbath, I. Krop, T. Sanft, A. Silber, J. Du, W. Amy, M. Lustberg, L. Pusztai. Use of DiviTum®TKa assay to assess CDK4/6 inhibitor medication compliance and drug interactions abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-09-28.