Results from a Hoosier Cancer Research Network study in triple negative breast cancer, led by researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, were recently published in npj Breast Cancer.

The purpose of the multi-site, phase II study, BRE09-146, “PARP Inhibition After Preoperative Chemotherapy in Patients with Triple Negative Breast Cancer or ER/PR+, HER2 Negative With Known BRCA1/2 Mutations,” was to evaluate 2-year disease-free survival (DFS) in patients treated with single agent cisplatin versus cisplatin in combination with the PARP inhibitor rucaparib following preoperative chemotherapy. Researchers also evaluated the safety and tolerability of this combination. Kathy D. Miller, MD (pictured), was the sponsor-investigator of the study. Dr. Miller is the Ballvé Lantero Professor of Oncology and a professor of medicine in the Indiana University School of Medicine and associate director of clinical research in the IU Simon Comprehensive Cancer Center.

Between February 2010 and May 2013, 128 patients were enrolled: 6 patients in safety cohort 2 and 122 patients in the randomized, intent-to-treat portion of the study. Study authors concluded that the addition of rucaparib to cisplatin did not increase 2-year or 5-year DFS. More than two-thirds of patients completed the planned four cycles of cisplatin, while only 50.8% percent of patients completed the planned 24 weeks of rucaparib maintenance. Eleven patients declined to start maintenance therapy, often due to the cost of frequent travel to study sites or a desire for early reconstruction.

In the abstract, the authors discuss limitations of the study that left the original hypothesis unanswered. However, they highlighted several important findings. The authors reported the use of germline genetic testing was, and remains, underused. Since a substantial proportion of women with breast cancer carrying germline mutations do not qualify for testing by NCCN criteria, expansion of current testing guidelines should be considered, say the authors.

The authors also reported that given the heterogeneity of TNBC at the genomic level, a single therapeutic approach is less likely to be successful, and as a result a follow-up study, BRE12-158, was designed to exploit targetable alterations found by sequencing residual disease. (Results from the BRE12-158 study were recently presented at the San Antonio Breast Cancer Symposium and published in JAMA Oncology.)

Study authors included: Maitri Kalra¹, Yan Tong², David R. Jones¹, Tom Walsh³, Michael A. Danso⁴, Cynthia X. Ma⁵, Paula Silverman⁶, Mary-Claire King³, Sunil S. Badve¹, Susan M. Perkins², and Kathy D. Miller¹ (sponsor-investigator).

¹Indiana University Melvin and Bren Comprehensive Cancer Center; ²Department of Biostatistics, Indiana University School of Medicine; ³University of Washington; ⁴Virginia Oncology Associates/US Oncology; ⁵Siteman Cancer Center, Washington University; ⁶University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center.

See the npj Breast Cancer journal article.

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 230 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 9,000 subjects have participated in Hoosier Cancer Research Network clinical trials.