Olaparib for advanced breast cancer

Olaparib, an oral PARP-inhibitor, has shown clinical benefit for HER2-negative advanced breast cancer patients carrying a germinal BRCA1/2 mutation. In a randomized Phase III trial, olaparib significantly prolonged progression-free survival as compared with chemotherapy of physician choice. Moreover, in the same trial, a prespecified subgroup analysis reported an overall survival benefit for patients not previously pretreated with chemotherapy for metastatic disease. This review focuses on available preclinical, pharmacokinetic and pharmacodynamic data regarding olaparib and clinical evidence of its antitumor efficacy (both as monotherapy and in combination) and tolerability in breast cancer patients. Open questions, such as use of appropriate biomarkers for patient selection and combination/sequencing with other anticancer drugs, are also addressed.

Download Full-text

Predicting Overall Survival and Progression-Free Survival Using Tumor Dynamics in Advanced Breast Cancer Patients

The AAPS Journal ◽

10.1208/s12248-018-0290-x ◽

2019 ◽

Vol 21 (2) ◽

Author(s):

Hyeong-Seok Lim ◽

Wan Sun ◽

Kourosh Parivar ◽

Diane Wang

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Progression Free Survival ◽

Advanced Breast ◽

Breast Cancer Patients ◽

Free Survival

Download Full-text

Ixabepilone plus capecitabine in advanced breast cancer patients with early relapse after adjuvant anthracyclines and taxanes: A pooled subset analysis of two phase III studies

The Breast ◽

10.1016/j.breast.2011.09.003 ◽

2012 ◽

Vol 21 (1) ◽

pp. 89-94 ◽

Cited By ~ 7

Author(s):

Jacek Jassem ◽

Luis Fein ◽

Mark Karwal ◽

Mario Campone ◽

Ronald Peck ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Advanced Breast ◽

Phase Iii ◽

Breast Cancer Patients ◽

Two Phase ◽

Early Relapse ◽

Subset Analysis ◽

Phase Iii Studies

Download Full-text

Final Results of a Randomized Phase III Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With a Dose-Intensified Epirubicin and Cyclophosphamide + Filgrastim as Neoadjuvant Treatment in Locally Advanced Breast Cancer: An EORTC-NCIC-SAKK Multicenter Study

Journal of Clinical Oncology ◽

10.1200/jco.2003.05.135 ◽

2003 ◽

Vol 21 (5) ◽

pp. 843-850 ◽

Cited By ~ 166

Author(s):

P. Therasse ◽

L. Mauriac ◽

M. Welnicka-Jaskiewicz ◽

P. Bruning ◽

T. Cufer ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Dose Intensity ◽

Advanced Breast ◽

Phase Iii ◽

Breast Cancer Patients

Purpose: To compare the efficacy of a standard anthracycline-based regimen to a dose-intensified anthracycline regimen in locally advanced breast cancer.Patients and Methods: Locally advanced breast cancer patients were randomly assigned onto a study comparing cyclophosphamide (C; 75 mg/m2orally days 1 to 14), epirubicin (E; 60 mg/m2intravenously [IV] days 1, 8), and fluorouracil (F; 500 mg/m2IV days 1, 8) six cycles every 28 days versus E (120 mg/m2IV day 1), C (830 mg/m2IV day 1), and granulocyte colony-stimulating factor (filgrastim; 5 μg/kg/d subcutaneously days 2 to 13) six cycles every 14 days. The study was designed to detect a 15% improvement; that is, from 50% to 65% in median progression-free survival (PFS) in favor of the dose-intensified regimen.Results: A total of 448 patients were enrolled over a period of 3 years. The median dose intensity delivered for C and E reached, respectively, 85% and 87% of that planned in the CEF arm and 96% and 95% of that planned in the EC arm. The dose-intensified arm was slightly more emetogenic and generated more grade 3 to 4 anemia but less febrile neutropenia episodes. After a median follow-up of 5.5 years, 277 events have been reported. The median PFS was 34 and 33.7 months for CEF and EC, respectively (P = .68), and the 5-year survival rate was 53% and 51% for CEF and EC, respectively (P = .94).Conclusion: Dose-intensified EC does not provide a measurable therapeutic benefit over CEF as neoadjuvant chemotherapy for unselected locally advanced breast cancer patients.

Download Full-text

Randomized Phase III Trial Comparing the New Potent and Selective Third-Generation Aromatase Inhibitor Vorozole With Megestrol Acetate in Postmenopausal Advanced Breast Cancer Patients

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.1.52 ◽

1999 ◽

Vol 17 (1) ◽

pp. 52-52 ◽

Cited By ~ 77

Author(s):

P. E. Goss ◽

E. P. Winer ◽

I. F. Tannock ◽

L. H. Schwartz on behalf of the North Ame

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Advanced Breast ◽

Phase Iii ◽

Tamoxifen Treatment ◽

Breast Cancer Patients ◽

Phase Iii Trial ◽

Treatment Groups ◽

Index Cancer

PURPOSE: To compare the efficacy and safety of vorozole (VOR) 2.5 mg once daily with that of megestrol acetate (MA) 40 mg four times per day as second-line therapy in postmenopausal women with advanced breast cancer whose disease progressed after tamoxifen treatment. PATIENTS AND METHODS: A total of 452 patients were enrolled onto an open, multicenter, randomized phase III trial comparing VOR to MA for tumor response, safety, and quality of life (as indicated by the Functional Living Index-Cancer score). RESULTS: Vorozole produced a response rate of 9.7%, compared with 6.8% for MA (P = .24). Clinical benefit (complete response + partial response + no change in > 6 months) was demonstrated in 23.5% and 27.2% of patients treated with VOR and MA, respectively (P = .42). Median duration of response was 18.2 months for VOR versus 12.5 months for MA (P = .074). There was no significant difference in time to progression or survival between the treatment groups. Discontinuation of treatment because of adverse events occurred less frequently in the VOR-treated group (3.1% v 6.2%; P = .18). Patients on the VOR arm reported significantly more nausea, hot flushes, arthralgia, upper respiratory tract infection, anorexia, and paresthesia, whereas those treated with MA had significantly more dyspnea, increased appetite, and weight increase. There was no difference between the two treatment groups in Functional Living Index-Cancer scores (total or subscales). However, when analyzed by objective response, patients with complete or partial responses (P = .032) or no change (P = .033) who were receiving VOR had significant improvement in the psychologic well-being subscale, compared with patients given MA. CONCLUSION: Vorozole is well tolerated and as effective as MA in the treatment of postmenopausal advanced breast cancer patients with disease progression after tamoxifen treatment.

Download Full-text