In the SABCS educational session Emerging Adjuvant Therapies: What's Ready for Prime Time? Ingrid Mayer, MD, discussed the use of targeted treatment with CDK4/6 inhibitors in hormone receptor positive (HR+) breast cancer added to endocrine therapy (ET) in the adjuvant setting. The CDK4/6i abemaciclib plus ET was approved in October for high risk HR+ breast cancer, defined as ≥stage IIB with ≥20% Ki67.
Dr. Mayer said the CDK4/6 inhibitors are ready for prime time, with a caveat that benefit was seen in those with lower Ki67 in the Monarch-E phase 3 trial of ET with or without abemaciclib.
An important unanswered question is how to reconcile the use of adjuvant abemaciclib with olaparib in patients with BRCA-mutated high risk breast cancer. Whether a year of olaparib, followed by abemaciclib plus ET, will provide benefit without long-term hematologic toxicity in this younger patient population remains to be determined, as will the role of newer ET in development. Translational correlative work on biospecimens collected in adjuvant trials are a “goldmine” for discovery and better patient selection. Nevertheless, late relapse remain the biggest unmet need in the early setting.
In discussing the treatment of triple negative breast cancer with residual disease, Sherene Loi, MD, PhD, suggested that since the quantity of immune infiltration is prognostic, immunity plays a role in this setting. Immuno-oncology (IO) agents might be effective in patients with tumor infiltrating lymphocytes. For those with BRCA germline mutations, olaparib could be combined with IO if reimbursed, although toxicity could be increased. My personal feeling is that for patients with residual disease, we need to prioritize new treatments. New antibody-drug conjugates combined with IO may be best, Dr. Loi said.
Andrew Tutt, MD, raised many questions in reviewing the use of PARP inhibitors for BRCA+ breast cancers. Do PARPi prevent new primary malignancies in this setting? Could PARPi enhance neoadjuvant chemotherapy or allow de-escalation in those with lower risk BRCA tumors or replace platinum in those with homologous recombination deficiency BC? Translational science work is underway to understand what clones survive and what PARPi resistant mechanisms occur in early breast cancer.
Dr. Lederman has no conflicts of interest to report and is a contributor for Doximity.
Illustration by April Brust