Association of initial abemaciclib dosing with duration of medication use in patients with stage II/III breast cancer on endocrine therapy.

Abstract

e12514 Background: The CDK 4/6 inhibitor abemaciclib is given to decrease risk of distant recurrence of breast cancer. However, its use has been limited by toxicity, in particular diarrhea, cytopenias, and fatigue. Data have shown that dose reduction of abemaciclib does not impact medication efficacy. We hypothesized that initiation of abemaciclib at lower than the FDA-approved dose will extend duration of medication use and minimize discontinuation due to adverse side effects. Methods: We performed a retrospective analysis of patients with hormone receptor positive, HER2 negative, stage 2 or 3 breast cancer at a single institution. Clinical and treatment data including age, BMI, menopausal status, and disease stage were collected. Patients were categorized by initial dose of abemaciclib (50mg BID, 100mg BID, 150mg BID, other) and compared via Fisher’s exact test. ANOVA testing was utilized to compare average duration (days) on each initial medication dosage. Results: 104 patients used adjuvant abemaciclib in combination with tamoxifen and/or an aromatase inhibitor. Mean age was 52, and 55 patients (53%) were premenopausal at time of diagnosis. In total, 3 patients (3%) started abemaciclib at 50mg BID, 32 (31%) started 100mg BID, 68 (65%) started 150mg BID, and one patient started 150mg daily. Average mean duration on abemaciclib before treatment discontinuation or censoring was 515 days (SD 270) for those initiated on 50mg BID, 223 days (SD 194) for those on 100mg BID, and 375 days (SD 256) for those on 150mg BID (p = 0.81). Of those who started on 50mg BID, no patients made dose adjustments during treatment. Of those who started on 100mg BID, 10 (31.25%) increased their dose, 4 (12.5%) decreased their dose, and 2 (6.25%) stopped the medication before completing 2 years without changing the dose. Of those who started on 150mg BID, 34 (50%) decreased their dose, mostly because of toxicity, and 7 (10.3%) stopped the medication before completing 2 years without changing the dose. To date, 30 patients have stopped abemaciclib prior to the two-year adjuvant period, 9 (28%) with starting dose 100 mg BID and 21 (30%) with starting dose 150 mg BID. Of note, 4 patients discontinued all endocrine therapy at the same time. Conclusions: Use of an abemaciclib dose lower than the FDA approved dose for initial adjuvant therapy was associated with a numerically lower likelihood of dose reduction although overall treatment duration and discontinuation rates are similar. Additional follow-up is required to determine the impact on total duration of therapy. These data support the need for additional prospective studies to examine the impact on alternative dosing regimens for abemaciclib on treatment adherence and long-term breast cancer outcomes.