Adjuvant Targeted Treatment of Early Hormone Receptor-positive HER2-negative Breast Cancer: Olaparib, Abemaciclib or Ribociclib - Which One, How and For Whom?

Abstract

With around 70000 new cases every year, breast cancer (BC) continues to be the most prevalent form of cancer. Hormone receptor-positive, HER2-negative (HR+/HER2-) BC is the most common type and accounts for around 70% of cases of early BC (eBC). The development of new drugs in recent years has significantly improved the survival of patients with eBC. Alongside established endocrine therapy (ET) options such as tamoxifen, aromatase inhibitors (AI), and GnRH analogs, additional treatment options such as CDK 4/6 inhibitors (abemaciclib and ribociclib) and the PARP inhibitor (olaparib) are now also available. To facilitate their use in clinical practice, this article provides a summary of the current information on the use of these drugs in clinical practice. Abemaciclib was approved for the adjuvant treatment of HR+/HER2- eBC in cases with positive lymph node involvement in 2022. The MonarchE trial showed that the addition of abemaciclib to ET improved invasive disease-free survival (iDFS) after 5 years by around 7.6% in patients with a high risk of recurrence. Ribociclib, another CDK4/6 inhibitor, was recently approved based on the results of the NATALEE trial. When combined with non-steroidal AIs, ribociclib showed a significant iDFS benefit of 4.9% after 4 years in node-positive and node-negative patients with a high risk of recurrence. The PARP inhibitor olaparib may be used to treat patients with BRCA germline mutation and HR+/HER2- eBC and a high risk of recurrence (CPS-EG score ≥ 3). The OlympiA approval study showed an iDFS benefit of 7.3% after four years and a benefit of 3.4% for overall survival. In summary, targeted therapies are expanding the range of adjuvant treatment options for patients with HR+/HER2- eBC and a higher risk of recurrence. Treating physicians are increasingly facing the challenge of choosing the optimal therapy for their patients. To do so, it is essential to carefully weigh up potential side effects against the expected benefit of treatment on a case-by-case basis.