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TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Dec 20; Vol. 38 (36), pp. 4274-4282. Date of Electronic Publication: 2020 Oct 29. - Publication Year :
- 2020
-
Abstract
- Purpose: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) in germline (g) BRCA1 / 2 mutation carriers. Olaparib Expanded, an investigator-initiated, phase II study, assessed olaparib response in patients with MBC with somatic (s) BRCA1 / 2 mutations or g/s mutations in homologous recombination (HR)-related genes other than BRCA1/ 2.<br />Methods: Eligible patients had MBC with measurable disease and germline mutations in non- BRCA1 / 2 HR-related genes (cohort 1) or somatic mutations in these genes or BRCA1 / 2 (cohort 2). Prior PARPi, platinum-refractory disease, or progression on more than two chemotherapy regimens (metastatic setting) was not allowed. Patients received olaparib 300 mg orally twice a day until progression. A single-arm, two-stage design was used. 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. Secondary endpoints included clinical benefit rate and progression-free survival (PFS).<br />Results: Fifty-four patients enrolled. Seventy-six percent had estrogen receptor-positive HER2-negative disease. Eighty-seven percent had mutations in PALB2, s BRCA1 / 2 , ATM, or CHEK2 . In cohort 1, ORR was 33% (90% CI, 19% to 51%) and in cohort 2, 31% (90% CI, 15% to 49%). Confirmed responses were seen only with g PALB2 (ORR, 82%) and s BRCA1 / 2 (ORR, 50%) mutations. Median PFS was 13.3 months (90% CI, 12 months to not available/computable [NA]) for g PALB2 and 6.3 months (90% CI, 4.4 months to NA) for s BRCA1 / 2 mutation carriers. No responses were observed with ATM or CHEK2 mutations alone.<br />Conclusion: PARP inhibition is an effective treatment for patients with MBC and g PALB2 or s BRCA1 / 2 mutations, significantly expanding the population of patients with breast cancer likely to benefit from PARPi beyond g BRCA1 / 2 mutation carriers. These results emphasize the value of molecular characterization for treatment decisions in MBC.
- Subjects :
- Adult
Aged
Aged, 80 and over
Female
Humans
Middle Aged
Mutation
Neoplasm Metastasis
Phthalazines pharmacology
Piperazines pharmacology
Poly(ADP-ribose) Polymerase Inhibitors pharmacology
Breast Neoplasms drug therapy
Homologous Recombination genetics
Phthalazines therapeutic use
Piperazines therapeutic use
Poly(ADP-ribose) Polymerase Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 38
- Issue :
- 36
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 33119476
- Full Text :
- https://doi.org/10.1200/JCO.20.02151