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 (original) (raw)
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Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015
Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) -associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50...
Asia-Pacific journal of clinical oncology, 2016
Olaparib is the first oral poly(ADP-ribose) polymerase inhibitor to be approved as maintenance monotherapy for treatment of patients with platinum-sensitive relapsed BRCA-mutated (BRCAm) serous ovarian cancer. This review provides practical guidance on the use of olaparib (capsule formulation) in the maintenance setting. The article focuses on the key toxicities that can arise with olaparib therapy and recommendations for their management. Nausea, vomiting, fatigue and anemia are the most commonly reported adverse events in olaparib clinical trials and are generally mild to moderate and transient in nature in most patients. Implementation of an effective and timely management plan can control many of the side effects. It is vital that health care providers effectively communicate the potential side effects of olaparib, as well as educate patients on management strategies to combat these symptoms. To this end, realistic expectations regarding the potential side effects need to be set...
Experience with the use of olaparib in patients with ovarian cancer
Gaceta de M�xico, 2020
Introduction: More than the twenty percent of ovarian cancers are hereditary, and most have BRCA mutations. The 30% of Mexican patients with the BRCA1 mutation have the BRCA1 gene exon 9-12del deletion founder mutation (BRCA1 ex9-12del). BR-CA-mutated tumors are more sensitive to PARP inhibitors such as olaparib. Objective: To show the clinical experience on the use of olaparib at Instituto Nacional de Cancerología in Mexico. Method: Ovarian cancer patients treated with olaparib from November 2016 to December 2018 were studied, and their characteristics, clinical response, progression-free survival (PFS) and toxicities were described. Results: Nineteen patients were assessed, with BRCA1 mutation being found in 78.9%, out of which 21.1% were carriers of the ex9-12del founder mutation. The median of PFS was 12 months; for patients treated on second and third line it was greater than 15 months, and for those treated with a fourth and subsequent line it was 8.3 months. Patients with the founder mutation had better results. Toxicities were like those reported in previous studies. Conclusions: Olaparib offers greater PFS benefit as maintenance therapy after a first and second relapse. Patients with founder mutation have had sustained PFS.
Drug Design, Development and Therapy, 2018
Epithelial ovarian cancer is the sixth most common cancer among women worldwide and the first cause of death among gynecological malignancies. Most of the patients present recurrent disease and unfortunately cannot be cured. The unsatisfactory results obtained with salvage chemotherapy have elicited investigators to search for novel biological agents capable of achieving a better control of the disease. In the setting of homologous recombination deficiency, the DNA errors that occur cannot be accurately repaired, and the treatment with poly(ADP-ribose) polymerase (PARP) inhibition results in definitive cell death in a process called synthetic lethality. As a result of two positive clinical trials, Olaparib was approved in 2014 by U.S. Food and Drug Administration and European Medicines Agency as the first-in-class PARP inhibitor. Olaparib is effective and well tolerated in homologous recombination deficient patients. Several studies with Olaparib have been conducted in the recurrent setting either as maintenance in platinum-responsive patients or as a single agent. Ongoing trials are focused on the use of olaparib as maintenance in the first-line ovarian cancer setting alone or in combination with antiangiogenic agents. Future perspectives will probably investigate the association of olaparib with novel agents as checkpoint inhibitors and PI3K-AKT inhibitors. The PARP inhibitor era is just at the beginning.
The Open Nursing Journal
Background: The Poly (ADP-ribose) polymerase inhibitor olaparib, acts against cancer cells in people with breast cancer pre-disposition gene mutations (BRCAm). Despite US and EU approval as a therapy for ovarian cancer patients with BRCAm, but research into olaparib therapy for breast cancer patients with BRCAm is in its infancy. Objective: As no systematic review has yet been undertaken to synthesise clinical trials looking at olaparib as a therapy for breast cancer patients with BRCAm, this systematic review aims to establish the current effectiveness of olaparib as a treatment for these patients. Methods: CINAHL, MEDLINE, Royal College of Nursing, Cochrane Library, Joanna Briggs Institute, Centre for Reviews and Dissemination, Internurse, Embase, Google Scholar and PubMed databases were searched, supplemented by a grey literature search, hand searching and cross-referencing. Authors independently reviewed and graded the studies also using Kmet et al. scoring system. Results: One ...
Clinical cancer research : an official journal of the American Association for Cancer Research, 2015
On December 19, 2014, the FDA approved olaparib capsules (Lynparza™, AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx™ (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international, multicenter, single-arm trial enrolled 137 patients with measurable, gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth daily until disease progression or unacceptable toxicity. The overall response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI, cough, arthr...