Tolerability, dose modification, and treatment compliance with adjuvant abemaciclib in high-risk early breast cancer:...

Abemaciclib plus endocrine therapy improves outcomes in high-risk hormone receptor-positive, HER2-negative early breast cancer (EBC) in monarchE, but real-world tolerability, dose modification, and treatment persistence in routine UK practice remain incompletely characterised.

A retrospective, multicentre study across 21 NHS Trusts of adults with high-risk EBC initiating adjuvant abemaciclib. The primary endpoint was treatment duration, whereas secondary endpoints included dose modifications, discontinuations, and toxicity profiles.

The cohort comprised 1026 patients (median age 54 years, range 22-87); 82.9% were Caucasian. Median abemaciclib duration was 15.5 months (range 0.2-24), 25.3% completed 24 months, and 54.9% remained on treatment at data cut-off. Overall, 19.7% discontinued abemaciclib, most commonly due to toxicity (15.9%), and 3.8% discontinued for disease progression. Dose modifications were frequent: 64.6% required ≥1 dose reduction, and 25.2% required ≥2 reductions. Common adverse events were diarrhoea (76.4%, grade ≥3 5.8%), neutropenia (43.4%, grade ≥3 8.2%), anaemia (33.2%, grade ≥3 0.3%), and transaminitis (17.2%, grade ≥3 1.8%). Acute kidney injury occurred in 21.6% (grade ≥3 0.4%), including one fatal case. Increasing diarrhoea and neutropenia grades were associated with first dose reduction; in multivariable analyses, grade ≥3 diarrhoea [adjusted odds ratio (OR) 7.62, 95% confidence interval (CI) 3.44-16.87, P < 0.001] and grade ≥3 neutropenia (adjusted OR 3.87, 3.87, 95% CI 2.11-7.11, P < 0.001) independently predicted dose reduction.

Although abemaciclib tolerability and discontinuation rates align with trial data, dose reductions are substantially more frequent in routine practice. Proactive toxicity management is vital to sustain treatment exposure, but longer follow-up is needed to establish how these reductions affect overall efficacy.