Author
Anne Floquet
Other affiliations: University of Bordeaux
Bio: Anne Floquet is an academic researcher from Argonne National Laboratory. The author has contributed to research in topics: Medicine & Ovarian cancer. The author has an hindex of 32, co-authored 153 publications receiving 6548 citations. Previous affiliations of Anne Floquet include University of Bordeaux.
Topics: Medicine, Ovarian cancer, Internal medicine, Oncology, Olaparib
Papers published on a yearly basis
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University of Oklahoma1, European Institute of Oncology2, Sungkyunkwan University3, Autonomous University of Barcelona4, University of New South Wales5, University of Bordeaux6, University of Paris-Sud7, Netherlands Cancer Institute8, Edinburgh Cancer Research Centre9, The Royal Marsden NHS Foundation Trust10, University of Toronto11, University of Texas MD Anderson Cancer Center12, Memorial Sloan Kettering Cancer Center13, Medical College of Wisconsin14, Harvard University15, AstraZeneca16
TL;DR: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression‐free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olAParib than with placebo.
Abstract: Background Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the o...
1,552 citations
Paris Descartes University1, University College London2, University of Sydney3, Harvard University4, Princess Margaret Cancer Centre5, Sheba Medical Center6, Pomeranian Medical University7, University of New South Wales8, University of Milan9, Saitama Medical University10, Claude Bernard University Lyon 111, The Royal Marsden NHS Foundation Trust12, AstraZeneca13, Institut Gustave Roussy14, Katholieke Universiteit Leuven15, Saint Petersburg State University16, Netherlands Cancer Institute17, Hannover Medical School18, Yonsei University19, Gynecologic Oncology Group20, University of São Paulo21
TL;DR: Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation.
Abstract: Summary Background Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2 ) mutation using a tablet formulation of olaparib. Methods This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0–1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6–12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients. Findings Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3–25·7]) than with placebo (5·5 months [5·2–5·8]; hazard ratio [HR] 0·30 [95% CI 0·22–0·41], p vs two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by 35 (18%) patients in the olaparib group and eight (8%) patients in the placebo group. The most common in the olaparib group were anaemia (seven [4%] patients), abdominal pain (three [2%] patients), and intestinal obstruction (three [2%] patients). The most common in the placebo group were constipation (two [2%] patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with an outcome of death. Interpretation Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable. Funding AstraZeneca.
1,280 citations
University of Texas MD Anderson Cancer Center1, Princess Margaret Cancer Centre2, Memorial Sloan Kettering Cancer Center3, Hebron University4, European Institute of Oncology5, Ottawa Hospital Research Institute6, University of Manchester7, Catholic University of the Sacred Heart8, French Institute of Health and Medical Research9, Auckland City Hospital10, Royal Brisbane and Women's Hospital11, Ohio State University12, Johns Hopkins University13, University of Washington14, University of California, Los Angeles15, University of Glasgow16, Royal Melbourne Hospital17, Foundation Medicine18, University College London19, Ghent University Hospital20
TL;DR: This trial assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity.
1,139 citations
University of Washington1, Princess Margaret Cancer Centre2, Royal Melbourne Hospital3, Foundation Medicine4, University of California, Los Angeles5, University of Texas MD Anderson Cancer Center6, BC Cancer Agency7, Ohio State University8, University College London9, Memorial Sloan Kettering Cancer Center10, University of Cambridge11, University of Arizona12, Hebron University13, Mayo Clinic14, Institut Gustave Roussy15, University of Glasgow16
TL;DR: The ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor, was assessed in ARIEL2, an international, multicentre, two-part, phase 2, open-label study.
Abstract: Summary Background Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor. Methods ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing. Findings 256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8–10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0–14·7) in the BRCA mutant subgroup, 5·7 months (5·3–7·6) in the LOH high subgroup, and 5·2 months (3·6–5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16–0·44, p Interpretation In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. These results extend the potential usefulness of PARP inhibitors in the treatment setting beyond BRCA mutant tumours. Funding Clovis Oncology, US Department of Defense Ovarian Cancer Research Program, Stand Up To Cancer—Ovarian Cancer Research Fund Alliance—National Ovarian Cancer Coalition Dream Team Translational Research Grant, and V Foundation Translational Award.
915 citations
University of Oklahoma1, European Institute of Oncology2, Sungkyunkwan University3, Hebron University4, University of New South Wales5, University of Bordeaux6, University of Paris-Sud7, Netherlands Cancer Institute8, University of Edinburgh9, University of Toronto10, University of Texas MD Anderson Cancer Center11, Memorial Sloan Kettering Cancer Center12, Medical College of Wisconsin13, Harvard University14, AstraZeneca15
TL;DR: Standard-of-care therapy for patients newly diagnosed with advanced ovarian cancer consists of frontline cytoreductive surgery and adjuvant platinum chemotherapy and approximately 70% of patients have a relapse within 3 years.
Abstract: (ed from N Engl J Med 2018;379:2495–2505)Standard-of-care therapy for patients newly diagnosed with advanced ovarian cancer consists of frontline cytoreductive surgery and adjuvant platinum chemotherapy. Approximately 70% of these patients have a relapse within 3 years.
481 citations
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01 Jan 2011
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.
2,187 citations
01 Jan 2014
TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.
1,988 citations
TL;DR: Current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness are discussed, and interesting lessons for the development of other therapies are provided.
Abstract: PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease. In addition, determining the optimal use of PARPi within drug combination approaches has been challenging. Nevertheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical approval provide interesting lessons for the development of other therapies. Here, we discuss current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness.
1,643 citations
University of Oklahoma1, European Institute of Oncology2, Sungkyunkwan University3, Autonomous University of Barcelona4, University of New South Wales5, University of Bordeaux6, University of Paris-Sud7, Netherlands Cancer Institute8, Edinburgh Cancer Research Centre9, The Royal Marsden NHS Foundation Trust10, University of Toronto11, University of Texas MD Anderson Cancer Center12, Memorial Sloan Kettering Cancer Center13, Medical College of Wisconsin14, Harvard University15, AstraZeneca16
TL;DR: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression‐free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olAParib than with placebo.
Abstract: Background Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the o...
1,552 citations
Tel Aviv University1, Katholieke Universiteit Leuven2, Fox Chase Cancer Center3, Sungkyunkwan University4, University College London5, Ruhr University Bochum6, Agostino Gemelli University Polyclinic7, Integra Telecom8, Technische Universität München9, Memorial Sloan Kettering Cancer Center10, AstraZeneca11, Merck & Co.12, University of Chicago13
TL;DR: Among patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo, and there was no significant between-group difference in health-related quality of life.
Abstract: Background Patients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate–ribose) polymerase (PARP) in...
1,321 citations