Abemaciclib dose escalation to maintain intensity (ADE-MI).

TPS618 Background: Abemaciclib is a an oral CDK4/6 inhibitor that is FDA-approved as adjuvant therapy for certain patients with early-stage HR+HER2- breast cancer in combination with endocrine therapy. The major toxicity of abemaciclib is diarrhea, which often occurs within the first 6-8 days of treatment initiation. Across several registrational trials, roughly 25% of patients with diarrhea from abemaciclib treatment required dose interruptions with roughly 20% required dose reductions. Because diarrhea happens early in the treatment course, one concern is this might dissuade people from continuing on or being fully adherent to adjuvant therapy. Incorporating strategies to minimize diarrhea may improve adherence and permit more patients to stay on the target recommended dose of 150mg BID for the full 2 years of adjuvant therapy. Our trial-in-progress evaluates dose escalation to address diarrhea as a cause of dose interruptions, reductions, and discontinuations, a strategy that has worked with other therapeutic agents. Specifically, our study tests the hypothesis that gradual up-titration of abemaciclib dose over a course of 4 weeks will decrease the rate of grade 3 or worse diarrhea. Methods: This is a post-marketing, single arm, phase IV trial for patients with high-risk early-stage HR+HER2- breast cancer who are eligible for treatment with adjuvant abemaciclib in combination with endocrine therapy. Fifty (50) subjects will be enrolled. Patients will gradually up-titrate the dose of abemaciclib over the course of 4 weeks before reaching the FDA recommended dose of 150mg BID (Table). The primary objective of this study is to increase the proportion of patients on the FDA recommended dose of abemaciclib at 3 months of treatment. At the significance level of 0.05, a minimum of 43 patients will achieve a power of at least 80% to detect the improvement (80% vs the historical control of 60%), using a two sized exact binomial test. Additional objectives are determining the number of days with greater than grade 1 diarrhea in the first month of treatment, determining rates of grade 3 or greater diarrhea, determining DFS and OS, and to assess patient reported outcomes regarding adverse events. The trial opened to enrollment on 12/21/2023. The first patient on the study was enrolled 1/25/2024. Clinical trial information: NCT06169371 . Table: see text