TRADE: a phase II trial to assess the tolerability of abemaciclib dose escalation in early-stage HR-positive/HER2-negative breast cancer

PURPOSE: Adjuvant abemaciclib with endocrine therapy (ET) improves clinical outcomes in patients with high-risk node-positive early-stage hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer, based on the monarchE trial. Patients may experience tolerability issues at the standard abemaciclib dose (150 mg twice daily [BID]), potentially leading to early treatment discontinuation, particularly within the initial weeks of therapy. TRADE is a prospective, single-arm, phase 2 study evaluating whether dose escalation of adjuvant abemaciclib improves drug tolerability. PATIENTS AND METHODS: Eligible patients had node-positive HR+/HER2- breast cancer and were candidates for adjuvant abemaciclib with ET. Participants initiated abemaciclib at 50 mg BID for two weeks, then escalated to 100 mg BID for two weeks, then escalated to the final dose level (150 mg BID). Dose escalation required the absence of ongoing grade 3-4 or persistent grade 2 toxicity. The primary endpoint, measured at 12 weeks, was a composite rate of abemaciclib discontinuation for any reason or inability to reach or maintain the target dose. RESULTS: In 89 evaluable patients, the initial dose escalation strategy significantly reduced the composite rate at 12 weeks versus a historical value of 40% from monarchE. In total, 26/89 participants (29.2%; 90% CI [21.3% - 38.2%]; p=0.023) met the endpoint: 6 (6.7%) for early discontinuation, 8 (9.0%) for inability to reach 150 mg, and 12 (13.5%) for dose reduction from 150 mg. The majority (70.8%) reached and maintained 150 mg BID dosing. CONCLUSION: Use of an adjuvant abemaciclib dose escalation strategy allowed more patients to reach and maintain target dosing at 12 weeks than observed in monarchE. Early discontinuation was infrequent, and 93.3% were continuing therapy at 12 weeks. This dosing strategy could be considered when initiating adjuvant abemaciclib.