Dana-Farber Cancer Institute researchers presented a range of significant findings at the 2024 San Antonio Breast Cancer Symposium (SABCS), covering novel treatment strategies and management approaches for various subtypes of breast cancer. The presentations included updates from key trials such as OlympiA, COMET, TBCRC 056, and studies evaluating new targeted therapies. These studies address critical questions in breast cancer care, from optimizing adjuvant therapy in BRCA-mutated cancers to exploring non-surgical options for low-risk disease and novel combinations for metastatic disease.
OlympiA Trial: Long-Term Benefits of Adjuvant Olaparib
Judy Garber, MD, MPH, presented longer-term follow-up data from the OlympiA trial, a phase 3 study evaluating adjuvant olaparib in patients with germline BRCA1/BRCA2 pathogenic variants and high-risk HER2-negative primary breast cancer. The updated results, with a median follow-up of 6.1 years, continue to support the use of olaparib in this setting, demonstrating sustained improvements in invasive disease-free survival, distant disease-free survival, and overall survival. These findings reinforce the role of PARP inhibitors in improving outcomes for patients with BRCA-mutated breast cancer following standard adjuvant chemotherapy, surgery, and radiation.
COMET Trial: Active Monitoring for Low-Risk DCIS
Ann Partridge, MD, presented patient-reported outcomes from the phase 3 COMET trial, which compared active monitoring to surgery with or without radiation for low-risk ductal carcinoma in-situ (DCIS). The study, which randomized 957 patients, found that active monitoring did not negatively impact quality of life, anxiety, depression, or worries about DCIS compared to standard surgical treatment over two years. These results challenge the conventional approach to low-risk DCIS, suggesting that active monitoring may be a viable option for select patients, potentially reducing the burden of overtreatment.
TBCRC 056: Neoadjuvant Niraparib and Dostarlimab in HR+/HER2- Breast Cancer
Erica Mayer, MD, MPH, presented initial results from the ER+/HER2- cohort of the randomized phase 2 TBCRC 056 trial, which investigated neoadjuvant niraparib (a PARP inhibitor) plus dostarlimab (an anti-PD-1 antibody) in patients with BRCA- or PALB2-mutated breast cancer. The study showed an 18.8% pathological complete response rate in this cohort, suggesting that this chemotherapy-free approach may be effective in a subset of patients with hormone receptor-positive, HER2-negative breast cancer and inherited genetic mutations. The trial also measured changes in stromal tumor-infiltrating lymphocytes (sTILs) and found a mean absolute increase of 11.9% after three weeks of niraparib treatment, supporting the hypothesis that PARP inhibitors can sensitize tumors to immune checkpoint inhibitors.
Atirmociclib Plus Letrozole in Metastatic Breast Cancer
Antonio Giordano, MD, PhD, presented data from an ongoing phase 1/2a trial of atirmociclib, a novel CDK4-selective inhibitor, in combination with letrozole as first-line treatment for HR-positive/HER2-negative metastatic breast cancer. In 34 patients who had not received prior anti-cancer medicine for metastatic disease and were CDK4/6 inhibitor-naive, the combination showed favorable safety and tolerability, with half of the 32 patients with measurable disease exhibiting a response to the treatment after a median follow-up of 11.1 months. These findings suggest that atirmociclib, which specifically blocks CDK4 and not CDK6, may offer a new treatment option for patients with metastatic breast cancer.
