Olaparib In Metastatic Breast Cancer
Summary
This research study is for patients with metastatic breast cancer. * Metastatic means that the cancer has spread beyond the breast. In addition, through genetic testing of the blood or tumor, an altered gene has been found that suggests the tumor may not be able to repair its genetic material (DNA) when it becomes damaged. * This aspect of the cancer may cause it to be more sensitive - that is, more effectively killed by certain types of drugs such as the study agent being evaluated in this trial, Olaparib. * Olaparib is a type of drug known as a PARP inhibitor. Some types of breast cancer and ovarian cancer share some basic features that make them sensitive to similar treatments. Information from those other research studies suggests that this drug may help to treat metastatic breast cancer. * This study will evaluate whether olaparib is effective in breast cancer patients whose tumor has a mutation in one of the other genes that function with BRCA1 and BRCA2 to repair damaged DNA .This mutation may have been inherited from a parent, or may have developed only in the tumor. * This study will also evaluate whether olaparib is effective in breast cancer patients whose tumor has a mutation in BRCA1 or BRCA2 that was acquired by the tumor, but not inherited.
Timeline
- Start
- 2018-04-01
- Primary completion
- 2025-07-30
- Completion
- 2026-06-30
Outcome
Mixed primary results
paper The primary endpoint was objective response rate (ORR); the null hypothesis (≤ 5% ORR) would be rejected within each cohort if there were four or more responses in 27 patients. PMID 33119476 ↗
paper In cohort 1, ORR was 33% (90% CI, 19% to 51%) and in cohort 2, 31% (90% CI, 15% to 49%). PMID 33119476 ↗
paper Among pts with a gPALB2m, the overall response rate (ORR) was 75% PMID 41604601 ↗
paper Although clinically meaningful, the ORR in pts with sBRCAm did not achieve the prespecified target. PMID 41604601 ↗
Publications
- Tung NM, Robson ME, Li T, Nanda R, Shah PD, Khoury K, Kimmick G, Santa-Maria C, Brufsky A, DeMeo M, Vieira JP, Carey LA, Wulf G, Domchek S, Krop IE, Wolff AC, Winer EP, Garber JE; Translational Breast Cancer Research Consortium (TBCRC). TBCRC 048 (Olaparib Expanded) Expansion Cohorts: Phase II Study of Olaparib Monotherapy for Patients With Metastatic Breast Cancer With Germline Mutations in PALB2 or Somatic Mutations in BRCA1 or BRCA2. J Clin Oncol. 2026 Mar 10;44(8):653-661. doi: 10.1200/JCO-25-02075. Epub 2026 Jan 28.
- Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. J Clin Oncol. 2020 Dec 20;38(36):4274-4282. doi: 10.1200/JCO.20.02151. Epub 2020 Oct 29.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Olaparib | Small molecule | 300 mg | Oral |