Dr Lopetegui-Lia on Adjuvant Therapy for Early-Stage TNBC With Residual Disease

“[One] area of high unmet need is [how to approcah treatment for] patients with early-stage, high-risk TNBC who receive neoadjuvant chemoimmunotherapy and then have residual disease at the time of surgery.”

Nerea Lopetegui-Lia, MD, a breast medical oncologist and assistant professor at The Ohio State University Comprehensive Cancer Center—James, discussed available treatment options for patients with early-stage high-risk triple-negative breast cancer (TNBC) who have residual disease at the time of surgery following neoadjuvant chemoimmunotherapy.

Clinical decision-making for these patients remains complex due to the lack of prospective data on optimal adjuvant therapies in this setting, Lopetegui-Lia began. Two commonly considered therapeutic agents are capecitabine and olaparib (Lynparza), she said. The choice between these agents is largely influenced by a patient’s BRCA mutation status, she noted. Capecitabine is typically used in patients who do not have germline BRCA1 or BRCA2 mutations, based on data from the phase 3 CREATE-X trial, which demonstrated significant disease-free survival (DFS) and overall survival (OS) benefits with capecitabine vs observation in patients with residual HER2-negative invasive breast cancer post-neoadjuvant chemotherapy, she stated. Notably, the phase 3 KEYNOTE-522 (NCT03036488) regimen—which includes neoadjuvant immunotherapy—was not approved at the time of the CREATE-X trial. Therefore, patients on that trial had not received neoadjuvant immunotherapy, she explained. As such, data on the efficacy of this combination for patients who have already received neoadjuvant chemoimmunotherapy are lacking, although combining capecitabine with pembrolizumab (Keytruda) appears to be safe, she cautioned.

For patients with residual disease who display germline BRCA1 or BRCA2 mutations, treatment with olaparib should be considered based on findings from the phase 3 OlympiA trial (NCT02032823), according to Lopetegui-Lia. This trial evaluated 1 year of adjuvant olaparib vs placebo in patients with HER2-negative, high-risk early breast cancer with pathogenic or likely pathogenic BRCA mutations. The use of olaparib in this population led to the agent’s FDA approval for use in chemotherapy-pretreated patients with germline BRCA-mutated, high-risk, HER2-negative early breast cancer after it generated improvements in invasive DFS, distant DFS, and OS.

Updated 10-year follow-up data presented at the 2024 San Antonio Breast Cancer Symposium confirmed the sustained benefit of olaparib in this population and addressed prior safety concerns, she reported. Specifically, the incidence of myelodysplastic syndrome, acute myeloid leukemia, or new primary malignancies—including breast, ovarian, fallopian tube, or pancreatic cancers—did not increase with olaparib compared with placebo, providing further reassurance regarding the long-term safety profile of this agent, she concluded.