Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study

Autor: Amit M. Oza, James Carmichael, David G. Huntsman, Hal W. Hirte, André Robidoux, Blake Gilks, Rinat Yerushalmi, Euan Macpherson, Marc Tischkowitz, Helen Mackay, Kenneth D. Swenerton, Mark Clemons, Karen A. Gelmon, Katia Tonkin
Rok vydání: 2011
Předmět:
Adult
Oncology
Canada
medicine.medical_specialty
Time Factors
endocrine system diseases
Receptor
ErbB-2
Administration
Oral
Antineoplastic Agents
Breast Neoplasms
Kaplan-Meier Estimate
Poly(ADP-ribose) Polymerase Inhibitors
Disease-Free Survival
Piperazines
Olaparib
chemistry.chemical_compound
Breast cancer
Undifferentiated Ovarian Carcinoma
Internal medicine
Ovarian carcinoma
Biomarkers
Tumor
medicine
Humans
Enzyme Inhibitors
Aged
Aged
80 and over
BRCA2 Protein
Ovarian Neoplasms
BRCA1 Protein
business.industry
Carcinoma
Cell Differentiation
Middle Aged
medicine.disease
Treatment Outcome
Receptors
Estrogen
chemistry
Response Evaluation Criteria in Solid Tumors
Mutation
PARP inhibitor
Phthalazines
Female
Neoplasm Recurrence
Local
Poly(ADP-ribose) Polymerases
Iniparib
Receptors
Progesterone
business
Ovarian cancer
Zdroj: The Lancet Oncology. 12:852-861
ISSN: 1470-2045
DOI: 10.1016/s1470-2045(11)70214-5
Popis: Summary Background Olaparib (AZD2281) is a small-molecule, potent oral poly(ADP-ribose) polymerase (PARP) inhibitor. We aimed to assess the safety and tolerability of this drug in patients without BRCA1 or BRCA2 mutations with advanced triple-negative breast cancer or high-grade serous and/or undifferentiated ovarian cancer. Methods In this phase 2, multicentre, open-label, non-randomised study, women with advanced high-grade serous and/or undifferentiated ovarian carcinoma or triple-negative breast cancer were enrolled and received olaparib 400 mg twice a day. Patients were stratified according to whether they had a BRCA1 or BRCA2 mutation or not. The primary endpoint was objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST). All patients who received treatment were included in the analysis of toxic effects, and patients who had measurable lesions at baseline were included in the primary efficacy analysis. This trial is registered at ClinicalTrials.gov, number NCT00679783. Findings 91 patients were enrolled (65 with ovarian cancer and 26 breast cancer) and 90 were treated between July 8, 2008, and Sept 24, 2009. In the ovarian cancer cohorts, 64 patients received treatment. 63 patients had target lesions and therefore were evaluable for objective response as per RECIST. In these patients, confirmed objective responses were seen in seven (41%; 95% CI 22–64) of 17 patients with BRCA1 or BRCA2 mutations and 11 (24%; 14–38) of 46 without mutations. No confirmed objective responses were reported in patients with breast cancer. The most common adverse events were fatigue (45 [70%] of patients with ovarian cancer, 13 [50%] of patients with breast cancer), nausea (42 [66%] and 16 [62%]), vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven [27%]). Interpretation Our study suggests that olaparib is a promising treatment for women with ovarian cancer and further assessment of the drug in clinical trials is needed. Funding AstraZeneca.
Databáze: OpenAIRE
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