Adjuvant Olaparib for Germline BRCA Carriers With HER2-Negative Early Breast Cancer: Evidence and Controversies

Stefania Morganti; Brittany L Bychkovsky; Philip D Poorvu; Ana C Garrido-Castro; Anna Weiss; Caroline C Block; Ann H Partridge; Giuseppe Curigliano; Nadine M Tung; Nancy U Lin; Judy E Garber; Sara M Tolaney; Filipa Lynce

doi:10.1093/oncolo/oyad123

Adjuvant Olaparib for Germline BRCA Carriers With HER2-Negative Early Breast Cancer: Evidence and Controversies

Oncologist. 2023 Jul 5;28(7):565-574. doi: 10.1093/oncolo/oyad123.

Authors

Stefania Morganti^{1

2

3

4

5

6}, Brittany L Bychkovsky^{1

2

3

7}, Philip D Poorvu^{1

2

3}, Ana C Garrido-Castro^{1

2

3

4}, Anna Weiss⁸, Caroline C Block^{1

2

3}, Ann H Partridge^{1

2

3}, Giuseppe Curigliano^{5

6}, Nadine M Tung^{3

9}, Nancy U Lin^{1

2

3}, Judy E Garber^{1

2

3

7}, Sara M Tolaney^{1

2

3}, Filipa Lynce^{1

2

3}

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
² Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
³ Harvard Medical School, Boston, MA, USA.
⁴ Broad Institute of MIT and Harvard, Boston, MA, USA.
⁵ Division of New Drugs and Early Drug Development, European Institute of Oncology, IRCCS, Milan, Italy.
⁶ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
⁷ Division of Genetics and Prevention Program, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ Department of Surgery, Division of Surgical Oncology, University of Rochester, Rochester, NY, USA.
⁹ Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Abstract

In the OlympiA study, 1 year of adjuvant olaparib significantly extended invasive disease-free survival and overall survival. The benefit was consistent across subgroups, and this regimen is now recommended after chemotherapy for germline BRCA1/2 mutation (gBRCA1/2m) carriers with high-risk, HER2-negative early breast cancer. However, the integration of olaparib in the landscape of agents currently available in the post(neo)adjuvant setting-ie, pembrolizumab, abemaciclib, and capecitabine-is challenging, as there are no data suggesting how to select, sequence, and/or combine these therapeutic approaches. Furthermore, it is unclear how to best identify additional patients who could benefit from adjuvant olaparib beyond the original OlympiA criteria. Since it is unlikely that new clinical trials will answer these questions, recommendations for clinical practice can be made through indirect evidence. In this article, we review available data that could help guide treatment decisions for gBRCA1/2m carriers with high-risk, early-stage breast cancer.

Keywords: OlympiA; adjuvant; early breast cancer; germline BRCA; olaparib.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

BRCA1 Protein / genetics
BRCA2 Protein / genetics
Breast Neoplasms* / drug therapy
Breast Neoplasms* / genetics
Female
Germ-Line Mutation
Humans
Phthalazines / therapeutic use

Substances

olympia
BRCA1 protein, human
BRCA1 Protein
olaparib
BRCA2 protein, human
BRCA2 Protein
Phthalazines