VP8-2021: Adjuvant abemaciclib combined with endocrine therapy (ET): Updated results from monarchE

Abstract

Adjuvant abemaciclib (CDK4 & 6 inhibitor) combined with ET provides significant and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in patients (pts) with HR+, HER2-, node-positive, high risk early breast cancer (EBC). Updated results with a median follow-up of 27 months are presented. Pts were randomized (1:1) to receive ET for up to 10 years (yrs) +/- abemaciclib for 2 yrs. Pts had ≥4+ axillary lymph nodes (ALN), or 1-3+ ALN and either grade 3 disease or tumor ≥5 cm (Cohort 1), or 1-3+ ALN and centrally tested Ki-67 ≥20% (Cohort 2). For the ITT (cohort 1+2) and Ki-67 populations, hazard ratio (HR) was estimated using Cox proportional hazard model (data cutoff 1 April 2021). Exploratory analyses estimated the piecewise HR within each yr in the ITT. With 90% of pts having completed or discontinued the 2-yr study treatment period, the magnitude of IDFS benefit deepened (HR=0.696, 95% CI=0.588, 0.823; nominal p<0.0001) and DRFS benefit was maintained (HR=0.687, 95% CI=0.571, 0.826; nominal p<0.0001). At 3 yrs, absolute improvement in IDFS and DRFS rates were 5.4% and 4.2%, respectively. Abemaciclib benefit deepened during the treatment period (estimated IDFS/DRFS piecewise HRs at yr 0-1 0.795/0.732, yr 1-2 0.681/0.675) and persisted after the 2-yr treatment period (2+ yr IDFS/DRFS piecewise HRs 0.596/0.692). Estimated IDFS rates in the control arm of Cohort 1 (Ki-67 High vs Low) confirmed the prognostic value of Ki-67; however, abemaciclib benefit was consistent regardless of Ki-67 index (table). Overall, AE profile was similar to the prior analysis.Table: VP8-2021IDFSDRFSAbemaciclib + ETETHR (95% CI)Abemaciclib + ETETHR (95% CI)ITT (Cohort 1+2), N = 5637 Patients, N280828290.696 (0.588, 0.823)280828290.687 (0.571, 0.826) Events, n232333191278 3-Year Rates88.8%83.4%90.3%86.1%Ki-67 High (Cohort 1+2), N = 2498 Patients, N126212360.663 (0.524, 0.839)126212360.639 (0.494, 0.827) Events, n11817297146 3-Year Rates86.8%80.8%88.3%84.3%Cohort 1-Ki-67 High, N = 2003 Patients, N10179860.626 (0.488, 0.803)10179860.599 (0.456, 0.787) Events, n10415885135 3-Year Rates86.1%79.0%87.8%82.6%Cohort 1-Ki-67 Low, N = 1914 Patients, N9469680.704 (0.506, 0.979)9469680.679 (0.473, 0.975) Events, n62865073 3-Year Rates91.7%87.2%93.1%89.1% Open table in a new tab The benefit of adjuvant abemaciclib added to ET is strengthened within and beyond the 2-yr treatment period for pts with HR+, HER2-, node-positive, high risk EBC. High Ki-67 was prognostic, but not predictive of abemaciclib benefit. Safety profile remains acceptable for pts with EBC treated with curative intent.