Amit M Oza

University Health Network, Toronto, Ontario, Canada

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Publications (176)1409.71 Total impact

  • International journal of radiation oncology, biology, physics 09/2015; DOI:10.1016/j.ijrobp.2015.09.009 · 4.26 Impact Factor
  • S Lheureux · K Karakasis · A M Oza
    07/2015; DOI:10.1016/j.canep.2015.07.002
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    ABSTRACT: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial. ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I-IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb-IV), with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m(2) of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6-56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the bevacizumab group). Our results showed evidence of non-proportional hazards, so we used the difference in restricted mean survival time as the primary estimate of effect. No overall survival benefit of bevacizumab was recorded (restricted mean survival time 44·6 months [95% CI 43·2-45·9] in the standard chemotherapy group vs 45·5 months [44·2-46·7] in the bevacizumab group; log-rank p=0·85). In an exploratory analysis of a predefined subgroup of 502 patients with poor prognosis disease, 332 (66%) died (174 in the standard chemotherapy group and 158 in the bevacizumab group), and a significant difference in overall survival was noted between women who received bevacizumab plus chemotherapy and those who received chemotherapy alone (restricted mean survival time 34·5 months [95% CI 32·0-37·0] with standard chemotherapy vs 39·3 months [37·0-41·7] with bevacizumab; log-rank p=0·03). However, in non-high-risk patients, the restricted mean survival time did not differ significantly between the two treatment groups (49·7 months [95% CI 48·3-51·1]) in the standard chemotherapy group vs 48·4 months [47·0-49·9] in the bevacizumab group; p=0·20). An updated analysis of progression-free survival showed no difference between treatment groups. During extended follow-up, one further treatment-related grade 3 event (gastrointestinal fistula in a bevacizumab-treated patient), three grade 2 treatment-related events (cardiac failure, sarcoidosis, and foot fracture, all in bevacizumab-treated patients), and one grade 1 treatment-related event (vaginal haemorrhage, in a patient treated with standard chemotherapy) were reported. Bevacizumab, added to platinum-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer. The National Institute for Health Research through the UK National Cancer Research Network, the Medical Research Council, and Roche. Copyright © 2015 Oza et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
    The Lancet Oncology 06/2015; 15(8). DOI:10.1016/S1470-2045(15)00086-8 · 24.69 Impact Factor
  • Cancer 06/2015; 121(18). DOI:10.1002/cncr.29484 · 4.89 Impact Factor
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    ABSTRACT: The prognosis for women with recurrent and metastatic endometrial cancer is poor, and improved therapies are needed. The mammalian target of rapamycin (mTOR) pathway is an important target, and mTOR inhibitors show clinical activity in endometrial cancer. An open-label, multicenter, randomized, phase II trial of oral ridaforolimus compared with progestin or investigator choice chemotherapy (comparator) was undertaken in women with metastatic or recurrent endometrial cancer who had progressive disease following one or two lines of chemotherapy and no hormonal therapy. The primary end point was progression-free survival (PFS) assessed by independent radiologic review. One hundred thirty patients were enrolled (64 received ridaforolimus and 66 received the comparator), and median age was 66 years. Treatment discontinuation as a result of adverse events was 33% with ridaforolimus versus 6% with the comparator, with common (> 10%) grade 3 toxicities being hyperglycemia, anemia, and diarrhea. Thirty-eight percent (ridaforolimus) versus 71% (comparator) of patients discontinued treatment as a result of disease progression. Median PFS at the protocol prespecified interim analysis with 58 PFS events (primary end point) was 3.6 months (95% CI, 2.7 to 7.3 months) for ridaforolimus and 1.9 months (95% CI, 1.9 to 2.3 months) for the comparator (hazard ratio, 0.53; 95% CI, 0.31 to 0.90; P = .008). PFS rate for ridaforolimus versus comparator was 48% versus 18% at 16 weeks and 38% versus 15% at 24 weeks. Objective response rate for ridaforolimus versus comparator was 0% versus 4% (P = .925), and stable disease was achieved in 35% versus 17% of patients (P = .021). Oral ridaforolimus shows encouraging activity in advanced endometrial cancer but is associated with significant toxicity. Inhibition of the PI3K/Akt/mTOR pathway may be a viable therapeutic target. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 06/2015; DOI:10.1200/JCO.2014.58.8871 · 18.43 Impact Factor
  • Gynecologic Oncology 06/2015; 138(2). DOI:10.1016/j.ygyno.2015.06.014 · 3.77 Impact Factor
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    ABSTRACT: The diagnosis, investigation, and management of ovarian cancer are in a state of flux-balancing ever rapid advances in our understanding of its biology with 3 decades of clinical trials. Clinical trials that started with empirically driven selections have evolved in an evidence-informed manner to gradually improve outcome. Has this improved understanding of the biology and associated calls to action led to appropriate changes in therapy? In this review, the authors discuss incorporating emerging data on biology, combinations, dose, and scheduling of new and existing agents with patient preferences in the management of women with ovarian cancer. Cancer 2015. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2015 The Authors. American Cancer Society.
    Cancer 06/2015; 121(18). DOI:10.1002/cncr.29481 · 4.89 Impact Factor
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    ABSTRACT: Introduction: Olaparib (Lynparza®) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has become the first 'personalized' therapy available for patients with BRCA mutation-positive ovarian cancer (OC). A capsule formulation of the drug has recently received approval for use in this population for platinum-sensitive recurrent disease for maintenance therapy following platinum-based chemotherapy in Europe and as third- or fourth-line platinum-sensitive therapy in the USA. Areas covered: This article reviews the development of olaparib in OC with a focus on safety evaluation. Data are based on published literature and reports available from the olaparib development program database. Expert opinion: Oral olaparib 400 mg twice daily has acceptable tolerability when administered as maintenance monochemotherapy in women with relapsed OC. The common toxicities - nausea/vomiting, fatigue and anemia - are mild or moderate in severity and appear consistent across subgroups (BRCA carriers/wild-type). Though the risk is low, long-term monitoring of patients is warranted to determine the potential risk for hematological complications such as anemia, myelodysplastic syndrome or acute myeloid leukemia.
    Expert Opinion on Drug Safety 06/2015; 14(8):1-12. DOI:10.1517/14740338.2015.1045875 · 2.91 Impact Factor
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    ABSTRACT: Optimal management of women with early stage GCT presents a management conundrum - they have excellent prognosis but a third will relapse. Advances uncovering the molecular characteristics of GCTs have not been matched by improvements in our understanding and treatment. Stage I GCT patients referred to Auckland City Hospital (1955-2012) and Princess Margaret Cancer Centre (1992-2012) were identified. Baseline characteristics, histopathology and outcomes were recorded retrospectively. One hundred and sixty stage I GCT patients were identified with median age of 49 years. Median follow-up was 7.0 years (range 0.1-44.2 years). Fifty-one patients (32%) relapsed with a median time to relapse (TTR) of 12.0 years (1.3-17.7 years) - 20 initial relapses occurred 10 years post-diagnosis. Higher relapse rates (43% vs. 24% p=0.02) and shorter TTR (10.2 vs. 16.2 years p=0.007) were seen with stage Ic versus stage Ia disease. Cyst rupture was associated with increased relapse (p=0.03). Surgery was the main therapeutic modality at relapse. Eighty six percent of patients received non-surgical management at least once post-relapse. Clinical benefit rate was 43% with chemotherapy, 61% with hormonal therapy and 86% with radiation. Five- and 10-year overall survival (OS) were 98.5 and 91.6%, respectively. Median OS was similar in patients with (24.3 years) and without relapse (22.3 years). Surgery remains fundamental at diagnosis and relapse. Caution should be exercised in recommending adjuvant chemotherapy at initial diagnosis given OS was greater than 20 years even with relapse. Hormonal therapy at relapse appears encouraging but needs further assessment. Novel treatment strategies need exploration with international collaboration essential for this. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 05/2015; 138(2). DOI:10.1016/j.ygyno.2015.05.011 · 3.77 Impact Factor
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    ABSTRACT: DepoVax is an innovative and strongly immunogenic vaccine platform. Survivin is highly expressed in many tumor types and has reported prognostic value. To generate tumor-specific immune response, a novel cancer vaccine was formulated in DepoVax platform (DPX-Survivac) using survivin HLA class I peptides. Safety and immune potency of DPX-Survivac was tested in combination with immune-modulator metronomic cyclophosphamide in ovarian cancer patients. Almost all the patients receiving the therapy produced antigen-specific immune responses; higher dose vaccine and cyclophosphamide treatment generating significantly higher magnitude responses. Strong T cell responses were associated with differentiation of naïve T cells into central/effector memory and late differentiated polyfunctional antigen-specific CD4+ and CD8+ T cells. This approach enabled rapid de novo activation/expansion of vaccine antigen-specific CD8+ T cells and provided a strong rationale for further testing to determine clinical benefits associated with this immune activation. These data represent vaccine induced T cell activation in a clinical setting to a self tumor antigen previously described only in animal models.
    OncoImmunology 05/2015; 4(8):00-00. DOI:10.1080/2162402X.2015.1026529 · 6.27 Impact Factor
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    ABSTRACT: Background: Low-grade serous (LGS) carcinomas of the ovary, fallopian tube and primary peritoneum are a unique subset of serous carcinomas for which current therapies (chemotherapy, hormonal) have demonstrated limited efficacy. KRAS or BRAF mutations, which activate the RAS/RAF/MEK/ERK signaling pathway, are present in many LGS carcinomas. Binimetinib is a potent inhibitor of MEK1/2, a key component of the RAS/RAF/MEK/ERK pathway, and has demonstrated activity in other disease settings where dysregulation of this pathway is present. Methods: This is a 2-arm, open-label, 2:1 randomized Phase 3 study of binimetinib vs physician’s choice chemotherapy (pegylated liposomal doxorubicin, paclitaxel or topotecan) in patients with LGS carcinomas. Eligible patients must have LGS carcinoma that is recurrent or persistent following at least 1 prior platinum-based chemotherapy and no more than 3 prior lines of chemotherapy, and must have RECIST v1.1-defined measurable disease confirmed by blinded independent central review (BICR). Prior to randomization, confirmation of LGS diagnosis is required. Patients are eligible regardless of RAS/RAF mutational status; however, tumor tissue will be retrospectively analyzed for mutations in RAS/RAF and other genes. Prior treatment with a MEK inhibitor or BRAF inhibitor is prohibited. Randomization is stratified by last platinum-free interval and number of prior systemic therapy regimens. The primary endpoint is progression-free survival as determined by the BICR; secondary endpoints include overall survival, overall response, duration of response, disease control rate, safety, quality of life and pharmacokinetics of binimetinib. Binimetinib is administered 45 mg BID orally. Patients receive therapy until disease progression or unacceptable toxicity. Crossover is permitted from physician’s choice chemotherapy to binimetinib upon BICR-confirmed progression. This study will enroll 300 patients worldwide (NCT01849874). Clinical trial information: NCT01849874
    Journal of Clinical Oncology 05/2015; 33. · 18.43 Impact Factor
  • Gynecologic Oncology 05/2015; 138. DOI:10.1016/j.ygyno.2015.04.024 · 3.77 Impact Factor
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    ABSTRACT: Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3. The study was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer (OC). Eligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria. Because of toxicities observed in the first 23 pts, the initial starting dose of oral daily (od) cediranib was reduced from 45 mg to 30 mg. The primary endpoint was objective response rate at 16 weeks. This study was stratified into two arms: platinum-sensitive (PL-S) and platinum-resistant (PL-R). 74 pts were enrolled; 39 were PL-S and 35 PL-R, with a median age of 58 years [31-87]. In PL-S group, 10 partial responses (PR) and stable disease (SD) in 20 (51%) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts (66%) had SD. The main grade 3/4 toxicities were hypertension (24%), fatigue (17%) and diarrhea (9%). The median progression-free survival for all patients was 4.9 months [3.9-7.0], 7.2 months [4.3-9] for PL-S and 3.7 months [2.6-4.5] for PL-R group. The median overall survival was 18.9 months (95% CI: 13.5-31.5); 27.7 months [17.8-43.3] for PL-S and 11.9 months [8.1-18.9] for PL-R group. Cediranib shows significant activity in recurrent platinum sensitive OC. The toxicities were expected and manageable at the dose of 30 mg od. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 04/2015; 138(1). DOI:10.1016/j.ygyno.2015.04.009 · 3.77 Impact Factor
  • Stephanie Lheureux · Amit M Oza
    The Lancet Oncology 04/2015; 16(5). DOI:10.1016/S1470-2045(15)70157-9 · 24.69 Impact Factor
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    ABSTRACT: A phase II study was performed to evaluate the efficacy and safety of single-agent RO4929097 (a gamma-secretase inhibitor) in patients with recurrent platinum-resistant ovarian cancer. Women with progressive platinum-resistant ovarian cancer treated with ≤ 2 chemotherapy regimens for recurrent disease were enrolled in this trial. Patients received oral RO4929097 at 20 mg once daily, 3 days on/4 days off each week of a three week cycle. The primary endpoint was progression-free survival (PFS) rate at the end of 4 cycles. Secondary objectives included assessment of the safety of RO4929097 and exploration of molecular correlates of outcome in archival tumour tissue and serum. Of 45 patients enrolled, 40 were evaluable for response. Thirty-seven (82%) patients had high-grade ovarian cancer. No objective responses were observed. Fifteen patients (33%) had stable disease as their best response,with a median duration of 3.1 months. Median PFS for the whole group was 1.3 months (1.2-2.5). Treatment was generally well tolerated with 10% of patients discontinuing treatment due to an adverse event. In high grade serous ovarian cancer patients, the median PFS trended higher when the expression of intracellular Notch (NICD) protein by immunohistochemistry was high versus low (3.3 versus 1.3 months p=0.09). No clear relationship between circulating angiogenic factors and PFS was found despite a suggestion of an improved outcome with higher baseline VEGFA levels. RO4929097 has insufficient activity as a single-agent in platinum-resistant ovarian cancer to warrant further study as monotherapy. Future studies are needed to explore the potential for cohort enrichment using NICD expression. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 03/2015; 137(2). DOI:10.1016/j.ygyno.2015.03.005 · 3.77 Impact Factor
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    ABSTRACT: Cancer treatment should allow patients to live better or longer lives, and ideally, both. Trial endpoints should show clinically meaningful improvements in patient survival or quality of life. Alternative endpoints such as progression-free survival, disease-free survival, and objective response rate have been used to identify benefit earlier, but their true validity as surrogate endpoints is controversial. In this Review we discuss the measurement, assessment, and benefits and limitations of trial endpoints in use for cancer treatment. Many stakeholders are affected, including regulatory agencies, industry partners, clinicians, and most importantly, patients. In an accompanying Review, reflections from individual stakeholders are incorporated into a discussion of what the future holds for clinical trial endpoints and design. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 01/2015; 16(1):e32-e42. DOI:10.1016/S1470-2045(14)70375-4 · 24.69 Impact Factor
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    ABSTRACT: Cancer is not one disease. Outcomes and endpoints in trials should incorporate the therapeutic modality and cancer type because these factors affect clinician and patient expectations. In this Review, we discuss how to: define the importance of endpoints; make endpoints understandable to patients; improve the use of patient-reported outcomes; advance endpoints to parallel changes in trial design and therapeutic interventions; and integrate these improvements into trials and practice. Endpoints need to reflect benefit to patients, and show that changes in tumour size either in absolute terms (response and progression) or relative to control (progression) are clinically relevant. Improvements in trial design should be accompanied by improvements in available endpoints. Stakeholders need to come together to determine the best approach for research that ensures accountability and optimises the use of available resources. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 01/2015; 16(1):e43-e52. DOI:10.1016/S1470-2045(14)70380-8 · 24.69 Impact Factor
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    ABSTRACT: Purpose: Veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase 1 trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase 2 trial to determine the response rate of veliparib in combination with cyclophosphamide compared to cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC). Experimental Design: Adult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the combination was allowed at disease progression. Results: Seventy-five patients were enrolled and 72 were evaluable for response; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen. Treatment was well tolerated. One complete response was observed in each arm, with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm. Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair; none of the detected genetic alterations were significantly associated with treatment benefit. Conclusions: This is the first trial that evaluated single agent, low dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression free survival. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 01/2015; 21(7). DOI:10.1158/1078-0432.CCR-14-2565 · 8.72 Impact Factor
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    ABSTRACT: The Brief Family History Questionnaire (bFHQ) was developed to identify endometrial cancer patients whose family histories suggest Lynch syndrome (LS). We compared the bFHQ, Extended Family History Questionnaire (eFHQ) and dictated medical records (DMR) to determine which family history screening strategy is superior in identifying LS in unselected women with newly diagnosed endometrial cancer that have undergone universal germline testing. Prospective cohort study recruiting women with newly diagnosed endometrial cancer to evaluate screening strategies to identify LS. Participants completed bFHQ and eFHQ, had tumor assessed with immunohistochemistry (IHC) for mismatch repair proteins (MMR) and micro-satellite instability testing and underwent universal germline testing for LS. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) were compared between the family history screening strategies as well as IHC. 118 of 182 eligible patients (65%) consented; 87 patients (74%) were evaluable with both family history and germline mutation status. Median age was 61years (range 26 - 91). All 7 patients with confirmed LS were correctly identified by bFHQ, compared to 5 and 4 by eFHQ and DMR, respectively. The sensitivity, specificity, PPV and NPV values of bFHQ were 100%, 76.5%, 25.9% and 100%, respectively, performing similar to IHC testing. While eFHQ was more specific than bFHQ (86.7% vs. 76.5%, p=0.007), 2 cases of LS were missed. The patient-administered bFHQ effectively identified women with confirmed LS and is a good screening tool to triage women with endometrial cancer for further genetic assessment. Copyright © 2014. Published by Elsevier Inc.
    Gynecologic Oncology 12/2014; 136(2). DOI:10.1016/j.ygyno.2014.12.023 · 3.77 Impact Factor
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    ABSTRACT: The poly(ADP-ribose) polymerase inhibitor olaparib has shown antitumour activity in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with or without BRCA1 or BRCA2 mutations. The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy, followed by olaparib maintenance monotherapy, versus chemotherapy alone in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer. In this randomised, open-label, phase 2 study, adult patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer who had received up to three previous courses of platinum-based chemotherapy and who were progression free for at least 6 months before randomisation received either olaparib (200 mg capsules twice daily, administered orally on days 1-10 of each 21-day cycle) plus paclitaxel (175 mg/m(2), administered intravenously on day 1) and carboplatin (area under the curve [AUC] 4 mg/mL per min, according to the Calvert formula, administered intravenously on day 1), then olaparib monotherapy (400 mg capsules twice daily, given continuously) until progression (the olaparib plus chemotherapy group), or paclitaxel (175 mg/m(2) on day 1) and carboplatin (AUC 6 mg/mL per min on day 1) then no further treatment (the chemotherapy alone group). Randomisation was done by an interactive voice response system, stratified by number of previous platinum-containing regimens received and time to disease progression after the previous platinum regimen. The primary endpoint was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1, analysed by intention to treat. Prespecified exploratory analyses included efficacy by BRCA mutation status, assessed retrospectively. This study is registered with, number NCT01081951, and has been completed. Between Feb 12 and July 30, 2010, 173 patients at 43 investigational sites in 12 countries were enrolled into the study, of whom 162 were eligible and were randomly assigned to the two treatment groups (81 to the olaparib plus chemotherapy group and 81 to the chemotherapy alone group). Of these randomised patients, 156 were treated in the combination phase (81 in the olaparib plus chemotherapy group and 75 in the chemotherapy alone group) and 121 continued to the maintenance or no further treatment phase (66 in the olaparib plus chemotherapy group and 55 in the chemotherapy alone group). BRCA mutation status was known for 107 patients (either at baseline or determined retrospectively): 41 (38%) of 107 had a BRCA mutation (20 in the olaparib plus chemotherapy group and 21 in the chemotherapy alone group). Progression-free survival was significantly longer in the olaparib plus chemotherapy group (median 12·2 months [95% CI 9·7-15·0]) than in the chemotherapy alone group (median 9·6 months [95% CI 9·1-9·7) (HR 0·51 [95% CI 0·34-0·77]; p=0·0012), especially in patients with BRCA mutations (HR 0·21 [0·08-0·55]; p=0·0015). In the combination phase, adverse events that were reported at least 10% more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia (60 [74%] of 81 vs 44 [59%] of 75), nausea (56 [69%] vs 43 [57%]), neutropenia (40 [49%] vs 29 [39%]), diarrhoea (34 [42%] vs 20 [27%]), headache (27 [33%] vs seven [9%]), peripheral neuropathy (25 [31%] vs 14 [19%]), and dyspepsia (21 [26%] vs 9 [12%]); most were of mild-to-moderate intensity. The most common grade 3 or higher adverse events during the combination phase were neutropenia (in 35 [43%] of 81 patients in the olaparib plus chemotherapy group vs 26 [35%] of 75 in the chemotherapy alone group) and anaemia (seven [9%] vs five [7%]). Serious adverse events were reported in 12 (15%) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 (21%) patients in the chemotherapy alone group. Olaparib plus paclitaxel or carboplatin followed by maintenance monotherapy significantly improved progression-free survival versus paclitaxel plus carboplatin alone, with the greatest clinical benefit in BRCA-mutated patients, and had an acceptable and manageable tolerability profile. AstraZeneca. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 12/2014; 16(1). DOI:10.1016/S1470-2045(14)71135-0 · 24.69 Impact Factor

Publication Stats

5k Citations
1,409.71 Total Impact Points


  • 2003–2015
    • University Health Network
      Toronto, Ontario, Canada
  • 1997–2015
    • University of Toronto
      • • Department of Medicine
      • • Department of Radiation Oncology
      Toronto, Ontario, Canada
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2011
    • St. James University
      Сент-Джеймс, New York, United States
    • Cedars-Sinai Medical Center
      • Cedars Sinai Medical Center
      Los Ángeles, California, United States
  • 2008
    • University of California, Davis
      Davis, California, United States
  • 2002
    • Ottawa Regional Cancer Foundation
      Ottawa, Ontario, Canada