A5076539645- PARP inhibition in cancer therapy
- Prostate Cancer Treatment and Research
- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Cancer Treatment and Pharmacology
- BRCA gene mutations in cancer
- Lung Cancer Research Studies
- Ovarian cancer diagnosis and treatment
- HER2/EGFR in Cancer Research
- DNA Repair Mechanisms
- Health Systems, Economic Evaluations, Quality of Life
- Radiation Therapy and Dosimetry
- Colorectal and Anal Carcinomas
- Economic and Financial Impacts of Cancer
- Breast Cancer Treatment Studies
- Statistical Methods in Clinical Trials
- Radiopharmaceutical Chemistry and Applications
- Cancer Immunotherapy and Biomarkers
- Neutropenia and Cancer Infections
- Multiple Myeloma Research and Treatments
- Chemotherapy-induced cardiotoxicity and mitigation
- Cell death mechanisms and regulation
AstraZeneca (United Kingdom)
2018-2024
AstraZeneca (Poland)
2020
Hôpital Lyon Sud
2019
Institut Bergonié
2018-2019
Seoul National University Hospital
2018-2019
Institut Gustave Roussy
2018-2019
Samsung Medical Center
2018
Institut Claudius Regaud
2018
The Christie NHS Foundation Trust
2018
Hôpital Cochin
2018
We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease progressed during previous treatment a next-generation hormonal agent. The results final analysis overall have not yet been reported. In an open-label, phase 3 trial, we randomly...
Abstract Background Olaparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor, with first-in-class approval (400 mg capsules BID) for BRCA-mutated advanced ovarian cancer. was recently found to be superior compared chemotherapy in HER2-negative gBRCAm MBC the Phase III OlympiAD trial. induces DNA damage and genomic instability tumors, which hypothesized result enhanced immunogenicity. Here, we assess if combination of olaparib an anti-programmed cell death ligand-1 (PD-L1) agent,...
Abstract Purpose: The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating DNA (ctDNA) testing as an additional method to identify patients mCRPC HRR alterations who may be eligible for treatment. Patients and Methods: Plasma samples collected during screening...
140 Background: Olaparib is a PARP inhibitor that has shown activity in relapsed gastric cancer (GC) when combined with chemotherapy. MEDIOLA assesses the efficacy and safety of chemo-free combination olaparib durvalumab, an anti-programmed cell death ligand-1 (PD-L1) agent patients (pts) solid tumors, including GC (NCT02734004). Methods: Eligible pts had following platinum-containing therapy. Pts received 300 mg PO BID for 4-wk run-in to allow serial biopsies, followed by durvalumab (1.5 g...
27 Background: ctDNA testing offers additional opportunities for homologous recombination repair (HRR) gene alteration determination in patients who are not able to access tumor tissue testing. Alteration ctDNA, BRCA1, BRCA2 and ATM alterations was performed retrospectively the PROfound study (phase 3 trial of olaparib versus physician’s choice abiraterone or enzalutamide men with HRR gene-mutated mCRPC [NCT02987543]). Methods: samples were sequenced at FMI, using FoundationOne Liquid CDx...
TPS287 Background: Docetaxel is the standard first-line chemotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed on an androgen receptor-targeted agent (ARTA; typically, abiraterone, enzalutamide, apalutamide, or darolutamide). However, most develop resistance, and median overall survival (OS) remains under 3 years. Preclinical studies have associated phosphoinositide 3-kinase (PI3K)/protein kinase (AKT)/phosphatase tensin homolog (PTEN)...
Abstract Background AKT pathway activation is implicated in endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) resistance patients (pts) with HR+/HER2– advanced breast cancer (ABC). In CAPItello-291, capivasertib (C, a potent of all 3 isoforms) + fulvestrant (F) significantly improved PFS versus placebo F pts aromatase inhibitor-resistant ABC. Simultaneous inhibition CDK4/6 pathways may delay CDK4/6i or re-sensitize tumors to ET plus CDK4/6i, leading clinical...
Abstract Background: Olaparib (Lynparza®) is approved for the treatment of gBRCAm HER2-negative MBC based on OlympiAD study results. Olaparib-induced DNA repair defects may attract tumor-infiltrating lymphocytes, upregulate programmed cell death ligand-1 (PD-L1) and release tumor neo-antigens upon death. Here, objective was to assess efficacy safety olaparib in combination with durvalumab (Imfinzi), a PD-L1 agent, (NCT02734004). Methods: Patients (pts) HER2-negative, were eligible; prior...
Abstract Background: Overcoming resistance to endocrine therapy in advanced breast cancer (ABC) is a major challenge, and there remains an unmet need for safe efficacious treatment options. AKT pathway activation implicated cyclin-dependent kinase 4/6 (CDK4/6) inhibitors patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) ABC. In the Phase 3 CAPItello-291 study, capivasertib (a potent inhibitor of all three isoforms) plus fulvestrant...
In oncology trials, treatment switching from the comparator to experimental regimen is often allowed but may lead underestimating overall survival (OS) of an therapy. This study evaluates impact control olaparib on OS using final data PROfound and compares validated adjustment methods estimate magnitude benefit with olaparib. The primary population (Cohort A) was included, alongside two populations approved for by European Medicines Agency US Food Drug Administration: BRCAm Cohort A+B...
Abstract Background: Olaparib (Lynparza®) is a PARP inhibitor that alters the repair of single-strand DNA breaks. Durvalumab (Imfinzi®) monoclonal antibody against programmed cell death ligand 1 (anti-PD-L1) promotes antitumor immune responses. MEDIOLA (NCT02734004) Ph I/II open-label, multicenter study enrolling patients (pts) across several tumor types (small-cell lung cancer, gastric germline BRCA-mutated [gBRCAm] BC, or platinum sensitive relapsed gBRCAm ovarian cancer). 34 pts with BC...
234 Background: A Phase II trial showed that addition of olaparib (O) to abiraterone (A) led significant radiographic progression-free survival benefit for patients (pts) with mCRPC vs placebo (P) + (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.44–0.97). We report predefined exploratory HRQoL analyses. Methods: This randomized, double-blind enrolled pts mCRPC, post-docetaxel. Pts were randomized (71 per arm) receive either O (300 mg bd, tablets) (1000 od) or P A; all received...
5539 Background: In the randomized Phase III PROfound trial (NCT02987543), olaparib significantly prolonged radiographic progression-free survival compared with physician’s choice of new hormonal agent (pcNHA, enzalutamide or abiraterone) in men mCRPC and HRR gene alterations, whose disease had progressed on prior NHA. Olaparib improved time to pain progression Cohort A. We report additional patient reported outcome measures HRQoL overall study population (Cohorts A+B). Methods: was assessed...
AKT pathway activation is implicated in resistance to endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) pts with HR+/HER2– ABC. In CAPItello-291, C+F significantly improved progression-free survival vs F aromatase inhibitor-resistant ABC (HR 0.60; 95% CI 0.51–0.71; p<0.001) pathway-altered tumours 0.50; 0.38–0.65; p<0.001). Simultaneous inhibition of CDK4/6 pathways may improve clinical outcomes by resensitising ET CDK4/6i. This phase Ib/III study evaluating the...
5538 Background: In the Phase III PROfound study (NCT02987543) olaparib significantly improved radiographic progression-free survival (primary endpoint) vs pcNHA (enzalutamide or abiraterone) in patients (pts) with mCRPC and homologous recombination repair (HRR) gene alterations. pts alterations BRCA1, BRCA2 and/or ATM (cohort A), time to pain progression was also by pcNHA. We report additional analyses evaluated overall population A B). Methods: Pts were randomized tablets (300 mg bid;...
<div>AbstractPurpose:<p>The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating DNA (ctDNA) testing as an additional method to identify patients mCRPC HRR alterations who may be eligible for treatment.</p>Patients and Methods:<p>Plasma...
<div>AbstractPurpose:<p>The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating DNA (ctDNA) testing as an additional method to identify patients mCRPC HRR alterations who may be eligible for treatment.</p>Patients and Methods:<p>Plasma...