Phase II, Open-Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of Olaparib, a Poly (ADP-Ribose) Polymerase Inhibitor, and Pegylated Liposomal Doxorubicin in Patients With <i>BRCA1</i> or <i>BRCA2</i> Mutations and Recurrent Ovarian Cancer

Kaye, Stan B.; Lubiński, Jan; Matulonis, Ursula A.; Ang, Joo Ern; Gourley, Charlie; Karlan, Beth Y.; Agarwal, Amit; Bell‐McGuinn, Katherine M.; Chen, Lee-may; Friedlander, Michael; Safra, Tamar; Vergote, Ignace; Wickens, Mark; Lowe, Elizabeth S.; Carmichael, James; Kaufman, Bella

doi:10.1200/jco.2011.36.9215

Cited by 437 publications

(283 citation statements)

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“…These low response rates, coupled with the results of our analysis, suggest that these single-agent treatments generallyhavelowefficacyinthissetting.Recently,therehavebeentrials evaluating the efficacy of novel treatment combinations such a trabectedin with PLD and canfosfamide with PLD compared with single-agent PLD in recurrent or platinum-resistant ovarian cancer [9,10]. In addition, a novel targeted agent, olaparib (a poly[ADP-ribose] polymerase inhibitor), was compared with single-agent PLD in BRCA1-or BRCA2-positive recurrent ovarian cancer patients [35]. These trials have not shown improvements in PFS or OS, although there was a trend toward additional toxic- [21], Topotecan I [22], Topotecan II [13], Canfosfamide [22], Patupilone [15].…”

Section: Single-agent Pldmentioning

confidence: 99%

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

et al. 2013

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Background. Recent studies suggest that carboplatin with pegylated liposomal doxorubicin (CϩPLD) is as efficacious as carboplatin with paclitaxel (CϩP) and possibly is more tolerable for ovarian cancer therapy. Pegylated liposomal doxorubicin(PLD)mayalsobeefficaciousandtolerableasmonotherapyin recurrent or platinum-resistant disease. We performed a metaanalysis of randomized trials in order to elucidate the role of PLD in ovarian cancer. Methods. We searched PubMed, Scopus, and ISI Web of Knowledge for studies comparing CϩPLD with CϩP and comparing PLD with another monotherapy. Summary hazard ratios (HRs) and relative risks with their corresponding 95% confidence intervals (CIs) were calculated using a fixed-effects model. Results. Three trials were included in the doublet regimen analysis, and five trials were included in the monotherapy regimen analysis. CϩPLD provided superior progression-free survival (PFS) (HR, 0.87; 95% CI, 0.78 -0.96) and similar overall survival (OS; HR, 0.95; 95% CI, 0.84 -1.07) compared with CϩP. There was no evidence of improved tolerability: CϩPLD had more gastrointestinal toxicity, anemia, thrombocytopenia, cutaneous toxicity, and mucositis/stomatitis, although there was less neutropenia, neuropathy, and alopecia. PLD monotherapy had similar PFS (HR, 0.99; 95% CI, 0.89 -1.11) and OS (HR, 0.99; 95% CI, 0.88 -1.11) to other monotherapies, but it was more tolerable. There was less neutropenia, anemia, thrombocytopenia, and gastrointestinal toxicity, although cutaneous toxicity was increased. Conclusion. CϩPLD had better PFS and similar OS compared with CϩP and had a very different toxicity profile. Therapy selection could be based on patient risks for side effects. PLD is as efficacious as other monotherapies and is more tolerable. The Oncologist 2013;18:1022-1031 Implications for Practice: Carboplatin with paclitaxel (CϩP) has been the standard first-line chemotherapy regimen for ovarian cancer patients; however, two large randomized trials of carboplatin and pegylated liposomal doxorubicin (CϩPLD) versus CϩP suggest that CϩPLD is as efficacious as CϩP and possibly is more tolerable. The results of our analysis showed that CϩPLD has better progression-free survival than CϩP and similar overall survival; however, we did not find CϩPLD to be more tolerable than CϩP. The toxicity profiles were very different, and therapy selection could reasonably be based on individual patient risks of side effects. Pegylated liposomal doxorubicin (PLD) is also a treatment option for recurrent or platinum-resistant ovarian cancer, but there is no clear distinction among any of the monotherapy options in this setting. The results of our analysis showed that PLD is as efficacious as other monotherapies and is more tolerable. Consequently, it may be the preferred agent in the palliative setting. INTRODUCTIONOvarian cancer is the leading cause of death from gynecologic malignancies in the United States [1]. Standard first-line treatment includes surgical debulking and platinum-based chemotherapy, us...

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Section: Single-agent Pldmentioning

confidence: 99%

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

et al. 2013

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“…This condition, like hereditary mutation in BRCA1-2, correlated to a good response to platinum-chemotherapy. However, Kaye et al, evaluated use of olaparib, a PARP inhibitor, compared to PLD in patients who relapsed within 12 months did not reach pre-specified endpoints, failing to demonstrate any advantage for olaparib [82].…”

Section: Parp Inhibitorsmentioning

confidence: 99%

Target Therapy in Platinum-Refractory/Resistant Ovarian Cancer: From Preclinical Findings to Current Clinical Practice

Staropoli¹,

Botta²,

Ciliberto³

et al. 2013

JCT

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Epithelial ovarian cancer (EOC) is the sixth most common malignancy in women. Ovarian tumors consist of several clinical and pathological entities that share an anatomic site. The gold standard treatment, both in front-line and in adjuvant setting, is represented by carboplatin/paclitaxel combination. Conversely, the second-line treatment is not well defined. The response to platinum is the major prognostic factor for survival. In this review we discuss the current views on platinum-refractory/resistant patient treatment only, which includes patients progressing or relapsing within 6 months from the last platinum-based course. Concerning this subgroup, the activity of several conventional drugs was confirmed in different trials without a significant impact in terms of overall survival. In the last years particular emphasis was given to targeted anti-angiogenetic therapy which produced a survival improvement with an acceptable toxicity profile. New "ad hoc" approaches, with a major attention to outcome-predictive factors, are eagerly awaited.

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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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Phase II, Open-Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of Olaparib, a Poly (ADP-Ribose) Polymerase Inhibitor, and Pegylated Liposomal Doxorubicin in Patients With BRCA1 or BRCA2 Mutations and Recurrent Ovarian Cancer

Abstract: The efficacy of olaparib was consistent with previous studies. However, the efficacy of PLD was greater than expected. Olaparib 400 mg twice per day is a suitable dose to explore in further studies in this patient population.

Cited by 437 publications

References 23 publications

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

Target Therapy in Platinum-Refractory/Resistant Ovarian Cancer: From Preclinical Findings to Current Clinical Practice

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

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