Author
Jean-Pierre Lotz
Bio: Jean-Pierre Lotz is an academic researcher. The author has contributed to research in topics: Population & Placebo. The author has an hindex of 2, co-authored 2 publications receiving 1583 citations.
Topics: Population, Placebo, Survival rate, Performance status, Olaparib
Papers
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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, Gynecologic Oncology Group19, Yonsei University20, 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
Cited by
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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
Tel Aviv University1, Katholieke Universiteit Leuven2, Fox Chase Cancer Center3, Sungkyunkwan University4, University College London5, Ruhr University Bochum6, Integra Telecom7, Agostino Gemelli University Polyclinic8, 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
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
Northwestern University1, Seattle Cancer Care Alliance2, Case Western Reserve University3, Washington University in St. Louis4, Ohio State University5, Stanford University6, University of California, San Diego7, Brigham and Women's Hospital8, Memorial Sloan Kettering Cancer Center9, University of Colorado Boulder10, University of Texas MD Anderson Cancer Center11, Mayo Clinic12, Fox Chase Cancer Center13, Harvard University14, Duke University15, University of Pennsylvania16, Vanderbilt University17, Yale University18, City of Hope National Medical Center19, University of Wisconsin-Madison20, University of Michigan21, University of California, San Francisco22, Johns Hopkins University23, University of South Florida24, University of Alabama at Birmingham25, University of Utah26, Roswell Park Cancer Institute27, National Comprehensive Cancer Network28
TL;DR: The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.
Abstract: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guerin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.
1,018 citations
TL;DR: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation.
Abstract: Background Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining mainte...
962 citations