Dr Litton on Navigating the Sequencing of PARP Inhibitors in Early-Stage TNBC


Jennifer K. Litton, MD, discusses challenges determining the optimal sequencing of PARP inhibitors in early-stage triple-negative breast cancer.

Jennifer K. Litton, MD, MHCM, medical oncologist, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses challenges in determining the optimal sequencing of PARP inhibitors in patients with early-stage triple-negative breast cancer (TNBC) and provides examples of factors she considers when making this decision in clinical practice.

The FDA approval of olaparib (Lynparza) for patients with high-risk, early-stage breast cancer who have a germline BRCA mutation and have previously received chemotherapy either before or after surgery represents a significant advancement in treatment options, Litton begins. The approval was based on findings from the phase 3 OlympiA trial (NCT02032823), in which olaparib significantly improved invasive disease-free survival vs placebo. Accordingly, olaparib is now an adjuvant standard of care for patients with TNBC or hormone receptor (HR)–positive disease and a germline BRCA mutation, particularly those with residual disease, Litton states.

However, the treatment paradigm for adjuvant therapy for high-risk breast cancer is rapidly evolving, with several highly effective drugs from different trials converging in this field, Litton notes. Currently, there is also a lack of data on the optimal sequencing of these agents, presenting a challenge in clinical decision-making, she adds. In light of this, the selection of PARP inhibitors in early disease stages is often up to an investigator's discretion and experience, Litton explains.

Litton states that in her own practice, continuing a PARP inhibitor plus immunotherapy in the adjuvant setting should be considered for patients with a germline BRCA mutation who had previously received immunotherapy, given the available safety data and potentially favorable outcomes with these agents compared with alternative treatments such as capecitabine (Xeloda).

For patients with HR-positive breast cancer, despite the approval of agents such as abemaciclib (Verzenio) and the anticipated approval of ribociclib (Kisqali) in this setting, a PARP inhibitor may still be preferred initially, Litton continues. However, there is a lack of data on using CDK4/6 inhibitors post–PARP inhibitor therapy. Individualized discussions with patients are essential to weigh the benefits and risks of each treatment option until more data become available to guide sequential therapy decisions, Litton concludes.

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