Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial

Oza, Amit M.; Cibula, David; Benzaquén, Ana; Poole, Christopher; Mathijssen, Ron H.J.; Sonke, Gabe S.; Colombo, Nicoletta; Špaček, Jiří; Vuylsteke, Peter; Hirte, H.; Mahner, Sven; Plante, Marie; Schmalfeldt, Barbara; Mackay, Helen; Rowbottom, Jacqui; Lowe, Elizabeth S.; Dougherty, Brian; Barrett, J. Carl; Friedlander, Michael

doi:10.1016/s1470-2045(14)71135-0

Cited by 486 publications

(345 citation statements)

References 28 publications

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“…In their report, the OS was 13.1 months for those receiving olaparib with paclitaxel versus 8.3 months for those receiving paclitaxel with placebo (p 5 .010) [29]. Additionally, Oza et al reported the results of a randomized phase II trial in which patients with recurrent platinum-sensitive ovarian cancer (38% BRCAmutated) were introduced to olaparib with chemotherapy or chemotherapy alone and found a longer PFS for those receiving olaparib plus chemotherapy (12.2 vs. 9.6 months; p 5 .0012) [30].…”

Section: Discussionmentioning

confidence: 99%

Phase II Study of Olaparib (AZD-2281) After Standard Systemic Therapies for Disseminated Colorectal Cancer

et al. 2016

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Background. Effective new agents for patients with colorectal cancer (CRC) with disease progression during standard therapy regimens are needed. We hypothesized that poly ADP ribose polymerase (PARP) inhibitor therapy in patients with CRC and inefficient tumor DNA repair mechanisms, such as those with high-level microsatellite instability (MSI-H), would result in synthetic lethality. Methods.This was an open-label phase II trial testing olaparib 400 mg p.o. b.i.d. for patients with disseminated, measurable CRC failing standard therapies with centrally confirmed tumor MSI status. The primary endpoint was the tumor response, assessed by RECIST, version 1.0.The secondary endpoints were safety/toxicity, progression-free survival (PFS), and overall survival (OS). Results. Thirty-three patients (20 microsatellite stable [MSS], 13 MSI-H) were enrolled. The median age for all

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Section: Discussionmentioning

confidence: 99%

Phase II Study of Olaparib (AZD-2281) After Standard Systemic Therapies for Disseminated Colorectal Cancer

et al. 2016

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“…Regarding the overall survival (OS) rate, only three clinical trials included complete datasets [5][6][7] . The OS information for these trials was not reported although it remains the ultimate treatment goal.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis on the PARP-inhibitor olaparib reveals therapeutic efficacy in ovarian cancer independent of BRCA1/2 mutation status

Vasconcelos¹,

Gaspar²

2016

Adv Mod Oncol Res

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Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising drugs for ovarian cancer treatment. This study investigated clinical trials of PARP inhibitors, in order to obtain a more complete prognosis of ovarian cancer patients, which is usually dependent on their BRCA1/2 mutation status. The PubMed database was searched using the key terms "PARP inhibitor OR olaparib OR veliparib OR niraparib OR rucaparib OR (BMN 673) AND (ovarian cancer OR solid tumors)", while narrowing the selection of the article type to "clinical trial" only. Women included in the study had been histologically diagnosed with recurrent high-grade serous ovarian-, fallopian tube-or primary peritoneal-carcinoma, regardless of the presence of BRCA germline mutation or platinum-sensitive disease recurrence. Data from three Phase I and eight Phase II clinical trials were obtained, two of which evaluated veliparib, eight olaparib and one niraparib. A total of 1042 patients with either high-grade serous ovarian-, fallopian tube-or primary peritoneal cancer were enrolled, of which 587 had a BRCA1/2 germline mutation and at least 370 were platinum-sensitive. The overall response rate (ORR) for patients who underwent treatment with olaparib was 44.5% (95% confidence interval = 0.396-0.496). Patients with BRCA1/2 mutation and those with wild-type BRCA1/2 showed no significant difference in ORR (p = 0.35), even when considering solely Phase II trials (p = 0.13). PARP inhibitors, particularly olaparib, proved effective in the management of ovarian cancer patients. This study identified the existence of patients who presented wild-type BRCA1/2 and possibly BRCA-independent homologous-recombination deficient tumors, or patients with wild-type BRCA1/2 and tumors presenting other forms of BRCAness, who benefit from treatment with olaparib.

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“…Six of the included studies were assessments of olaparib in populations of women with serous tumour h i stolog ies 12,22,25,26,29,37 . Five st ud ies con sidered systemic treatment in patients with recurrent ovarian cancer 16,21,32,33,35 .…”

Section: Search For Existing Systematic Reviews and Primary Literaturementioning

confidence: 99%

Systemic Therapy for Recurrent Epithelial Ovarian Cancer: A Clinical Practice Guideline

et al. 2017

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Objective The purpose of this guideline is to recommend systemic therapy options for women with recurrent epithelial ovarian cancer, including fallopian tube and primary peritoneal cancers. Methods This document updates the recommendations published in the 2011 Optimal Chemotherapy forRecurrent Ovarian Cancer guideline from Cancer Care Ontario. Draft recommendations were formulated based on evidence obtained through a systematic review of phase ii and iii randomized controlled trials (rcts). The draft recommendations underwent internal review by clinical and methodology experts, and external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline. ResultsThe primary literature search yielded thirty-six primary research papers representing thirty rcts that met the eligibility criteria. The guideline provides recommendations for patients with serous tumour histologies and with recurrent, platinum-resistant, and platinum-sensitive ovarian cancer. ConclusionsThe body of evidence from trials that included olaparib and bevacizumab consistently shows a benefit in progression-free survival (pfs) without a corresponding benefit in overall survival (os). The Working Group for this guideline designated pfs, which is associated with symptom control, as a critical outcome. A finding of net benefit can therefore be concluded based on significant differences in pfs. However, that benefit is not without identified harms. Given the identified harms, patient involvement in the decision-making process must take into consideration the side effect profiles of olaparib and bevacizumab within the context of improved pfs but minimal change in os.

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Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial

Cited by 486 publications

References 28 publications

Phase II Study of Olaparib (AZD-2281) After Standard Systemic Therapies for Disseminated Colorectal Cancer

Phase II Study of Olaparib (AZD-2281) After Standard Systemic Therapies for Disseminated Colorectal Cancer

Meta-analysis on the PARP-inhibitor olaparib reveals therapeutic efficacy in ovarian cancer independent of BRCA1/2 mutation status

Systemic Therapy for Recurrent Epithelial Ovarian Cancer: A Clinical Practice Guideline

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