Dr Hamilton on the Efficacy and Safety of Abemaciclib Plus ET in Elderly Patients With HR+/HER2- Breast Cancer

Erika P. Hamilton, MD, director, Breast and Gynecologic Cancer Research, Sarah Cannon Research Institute, discusses the efficacy and safety of adjuvant abemaciclib (Verzenio) plus endocrine therapy (ET) in patients with hormone receptor (HR)–positive, HER2-negative, high-risk early breast cancer according to age.

A significant proportion of patients with newly diagnosed breast cancer are older than 65. These patients experience a higher incidence of comorbidities and risk of developing toxicities with cancer therapy, necessitating specific guidance for treatment management in this high-risk subgroup.

A 4-year age group analysis of findings from the phase 3 monarchE trial (NCT03155997) was conducted to assess the benefit of this regimen for patients 65 years of age or older. In monarchE, patients were randomized to receive endocrine therapy for up to 10 years with or without 2 years of adjuvant abemaciclib. In this analysis, patients were grouped according to whether they were younger than 65 or 65 years of age or older. Efficacy and safety outcomes with the experimental regimen were assessed for each group.

Results showed that older patients derived a similar benefit from adjuvant abemaciclib as their younger counterparts, indicating that their cancers are not indolent. Moreover, patients maintained clinically meaningful reduction in the risk of developing invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) events with the experimental regimen regardless of age. At approximately 4 years of follow-up, the iDFS rate in the older age group was 82.0% with adjuvant abemaciclib vs 76.8% with endocrine therapy alone. This resulted in an absolute difference of 5.2% (HR, 0.767; 95% CI, 0.556-1.059). In patients younger than 65, these rates were 86.5% and 79.8%, respectively. The absolute difference in this population was 6.7% (HR, 0.646; 95% CI, 0.554-0.753).

Regarding safety, most older patients did not experience an increase in the incidence of all-grade adverse effects (AEs) vs younger patients. Notably, neutropenia, interstitial lung disease, and venous thromboembolism occurred at similar rates in both groups. However, older patients had a 5% higher likelihood of experiencing a serious (grade 3 or greater) AEsvs younger patients.

For example, AEs such as diarrhea and fatigue were less common overall but occurred more frequently at higher severity in the elderly population. Accordingly, treatment-related dose discontinuations and reductions were more frequent in the elderly population. The rate of drug discontinuation was 38% in patients older than 65, and 15% in those younger than 65. Overall, the agent still showed comparable tolerability in both age groups.

Disclosures: Dr Hamilton reported serving as a consultant or in an advisory role for AstraZeneca, Daiichi Sankyo, Ellipses Pharm, Genentech/Roche, Greenwich LifeSciences, ITeos Therapeutics, Janssen, Lilly, Loxo, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Pfizer, Relay Therapeutics, Seagen, Stemline Therapeutics, Theratechnologies, Tubulis GmbH, Verascity Science; she received institutional research funding from Abbvie, Accutar Biotech, Acerta Pharma, ADC Therapeutics, Akeso Biopharma, Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond Therapeutics, Bliss Biopharmaceutical, Boehringer Ingelheim, Cascadian Therapeutics, Clovis Oncology , Compugen, Context Therapeutics, Cullinan Oncology, Curis, CytomX Therapeutics, Daiichi Sankyo, Dana Farber Cancer Hospital, Dantari, Deciphera, Duality Biologics, eFFECTOR Therapeutics, Ellipses Pharma, Elucida Oncology, EMD Serono, Fujifilm, G1 Therapeutics, Genentech/Roche, H3 Biomedicine, Harpoon, Hutchison MediPharma, Immunogen, Immunomedics, Incyte, Infinity Pharmaceuticals, InventisBio, Jacobio, K-Group Beta, Karyopharm Therapeutics, Kind Pharmaceuticals, Leap Therapeutics, Lilly, Loxo, Lycera, MabSpace Biosciences, Macrogenics, MedImmune, Mersana, Merus, Millennium, Molecular Templates, Novartis , Nucana, Olema Pharmaceuticals, OncoMed, Onconova Therapeutics, Oncothyreon, ORIC Pharmaceuticals, Orinove, Orum Therapeutics, Pfizer, PharmaMar, Pieris Pharmaceuticals, Pionyr, Plexxikon, Prelude Therapeutics, ProfoundBio, Radius Health, Regeneron, Relay Therapeutics, Repertoire Immune Medicines, Rgenix, Seagen, Sermonix Pharmaceuticals, Shattuck Labs, Stem CentRx, Sutro Biopharma, Syndax, Syros Pharmaceuticals, Taiho Pharmaceutical, TapImmune Inc, Tesaro, Tolmar, Torque, Treadwell Therapeutics, Verastem, Zenith Epigenetics, and Zymeworks.