PARP Inhibitors Arrive for BRCA+ Breast Cancer

Silas Inman @silasinman
Published: Saturday, Mar 10, 2018

“There were differences in toxicity,” Tripathy said. “Anemia might be more frequent with talazoparib and neutropenia, although it is not seen as frequently as in the chemotherapy groups. I will point out that fatigue is a common event, although it might be a little more common with talazoparib.”

Ongoing PARP Inhibitor Studies

Combinations are a logical next step for the PARP inhibitors, with early findings already available for veliparib plus carboplatin and paclitaxel from the phase II BROCADE-2 trial.3 The median PFS was 14.1 months (95% CI, 11.5-16.2) for the veliparib arm and 12.3 months (95% CI, 9.3-14.5) for the placebo group (HR, 0.789; 95% CI, 0.536-1.162; P = .231). The ORR was 77.8% for veliparib versus 61.3% in the placebo group.

The phase III BROCADE-3 study is currently assessing the efficacy and tolerability of carboplatin and paclitaxel with veliparib or placebo for patients with HER2-negative BRCA-associated advanced breast cancer. The study has fully accrued with a primary completion date of May 31, 2018 (NCT02163694).

Several other single-agent trials are also underway. The phase III BRAVO trial is looking at niraparib for HER2-negative, BRCA-mutant advanced breast cancer, with results expected in May (NCT01905592). Additionally, the phase III OlympiA trial is comparing adjuvant olaparib with placebo as a treatment for patients with HER2-negative, germline BRCA-mutant breast cancer. The primary endpoint of the study is invasive disease-free survival, with a primary completion date in March 2020. Study enrollment in the trial is expected to end in April 2018, Tripathy said.

Outside of these studies, PARP inhibitors are being explored with a variety of partners, he noted. “Trials are ongoing in the adjuvant setting, in biomarker-specified BRCA-wild type and in combinations with radiation therapy, immunotherapy, signal transduction inhibitors, such as PI3K/mTOR, Wee1 kinase inhibitors, and CDK 4/6 inhibitors,” he said.

The phase II SWOG 1416 study is exploring other potential markers that could predict response to PARP inhibitors. This trial includes an arm of patients with germline BRCA mutations along with other arms to assess other DNA-repair–associated markers, such as high levels of homologous repair deficiency or mutations in homologous repair genes (NCT02595905). The estimated primary completion date for this study is in October 2021.

References

  1. Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. 2017;377:523-33. N Engl J Med. doi: 10.1056/NEJMoa1706450.
  2. Litton JK, Rugo HS, Ettl J, et al. A phase 3 trial comparing talazoparib, an oral PARP inhibitor, to physician’s choice of therapy in patients with advanced breast cancer and a germline BRCA-mutation. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS6-07.
  3. Han HS, Diéras V, Robson M, et al. Efficacy and tolerability of veliparib (V; ABT-888) in combination with carboplatin (C) and paclitaxel (P) vs placebo (Plc)+C/P in patients (pts) with BRCA1 or BRCA2 mutations and metastatic breast cancer: a randomized, phase 2 study. Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract S2-05.





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TitleExpiration DateCME Credits
Community Practice Connections™: Medical Crossfire®: Translating Lessons Learned with PARP Inhibition to the Treatment of Breast Cancer—Expert Exchanges on Novel Strategies to Personalize CareAug 29, 20181.5
Community Practice Connections™: 1st Annual International Congress of Oncology Pathology™: Towards Harmonization of Pathology and Oncology StandardsAug 30, 20182.0
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