Results of a deep-dive survey on practice patterns of oncologists and advanced practice providers utilizing PARP inhibitors as maintenance therapy for patients with ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18044-e18044
Author(s):  
Wendy Turell ◽  
Tariqa Ackbarali ◽  
Robert L. Coleman ◽  
Shannon Neville Westin ◽  
Judith Ann Smith
Keyword(s):  
Ovarian Cancer ◽  
Online Education ◽  
Maintenance Therapy ◽  
Patient Outcomes ◽  
Treatment Options ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Deep Dive ◽  
Barriers To Change ◽  
Education Activity

e18044 Background: Often diagnosed at an advanced stage, most patients with ovarian cancer will relapse. As several PARP inhibitors (PARPi) have recently been approved as maintenance, patients are presented with treatment options that extend the interval of disease remission. However, novel challenges exist as oncology teams are apprehensive of integrating PARPi in practice. Emphasis on building this competence is essential for patients to obtain the maximum benefit of maintenance PARP therapy. Methods: Oncology teams were invited to participate in a 1-hour live and online education activity broadcast from 2018-2019 at OMedLive.com for 12 months. The activity addressed clinical data on the use of PARPi as maintenance therapy, management of adverse events, and emerging strategies utilizing PARP inhibition. A deep-dive survey, including structured and open-ended questions, was conducted 2 to 4 months after participation and focused on changes in practice, barriers to change, and observed patient outcomes. Results: In total, 915 clinicians participated in the video-based activity. Sixty physicians and advanced practitioners opted to complete the deep-dive survey, 70% of whom have used PARP inhibitors as maintenance therapy. Practice improvements were reported for identifying patients likely to benefit from PARPi (90%), differentiating among approved PARPi (86%), counseling patients (85%), and team-based side effect management (95%). The top 3 barriers to utilization of PARPi were lack of reimbursement (23%), inability to anticipate patient outcomes (15%), and unfamiliarity with clinical guidelines (15%). Variations in responses to open-ended questions included persistent questions (n = 47) in need of responses before adopting PARPi, data needed to better inform decision-making (n = 49), major concerns about PARPi (n = 55), and the most challenging aspects of current patient management with PARPi (n = 39). Conclusions: Patient education yielded improvements in practical application and management of PARP inhibitors for patients with ovarian cancer. The thematic variations in open-ended responses may inform the design of tailored interventions to improve clinical integration of PARP inhibitors as maintenance therapy and different lines of treatment.

scholarly journals Germline PALB2 Variants and PARP Inhibitors in Endometrial Cancer

2021 ◽  
Vol 19 (11) ◽  
pp. 1212-1217
Author(s):  
Michael A. Cilento ◽  
Nicola K. Poplawski ◽  
Sellvakumaram Paramasivam ◽  
David M. Thomas ◽  
Ganessan Kichenadasse
Keyword(s):  
Endometrial Carcinoma ◽  
Treatment Options ◽  
Parp Inhibitors ◽  
Response To Treatment ◽  
Parp Inhibition ◽  
Ovarian Cancer Risk ◽  
Additional Question ◽  
Prostate Cancers ◽  
Risk Reducing ◽  
Female Carriers

PARP inhibitors are orally administered antineoplastic agents that affect the homologous recombination (HR) repair pathway, and are approved by the FDA for the treatment of ovarian, breast, pancreatic, and prostate cancers. This report presents a case of recurrent endometrial carcinoma occurring in a woman with a germline pathogenic PALB2 whole-exon deletion. This uncommon finding in a patient with endometrial carcinoma provided the opportunity to use a management strategy of PARP inhibition with olaparib, resulting in a prolonged response to treatment; however, disease progression eventually occurred. Further studies are required to elucidate the mechanisms underlying resistance to PARP inhibition, and the potential future treatment options in this setting. Current recommendations for risk management of female carriers of PALB2 variants focus on breast and ovarian cancer risk. This case raises the additional question of a potential role for risk-reducing hysterectomy in female carriers of PALB2 variants.

scholarly journals Poly-ADP-ribose polymerase inhibitor use in ovarian cancer: expanding indications and novel combination strategies

2019 ◽  
Vol 29 (5) ◽  
pp. 956-968 ◽  
Author(s):  
Emily Hinchcliff ◽  
Shannon Neville Westin ◽  
Graziela Dal Molin ◽  
Christopher J LaFargue ◽  
Robert L. Coleman
Keyword(s):  
Ovarian Cancer ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Combination Therapies ◽  
Combination Strategies ◽  
Polymerase Inhibitor

The use of poly(ADP-ribose) polymerase (PARP) inhibition is transforming care for the treatment of ovarian cancer, with three different PARP inhibitors (PARPi) gaining US Food and Drug Administration approval since 2014. Given the rapidly expanding use of PARPi, this review aims to summarize the key evidence for their use and therapeutic indications. Furthermore, we provide an overview of the development of PARPi resistance and the emerging role of PARPi combination therapies, including those with anti-angiogenic and immunotherapeutic agents.

scholarly journals First-line PARP inhibitors in ovarian cancer: summary of an ESMO Open - Cancer Horizons round-table discussion

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e001110
Author(s):  
Susana Banerjee ◽  
Antonio Gonzalez-Martin ◽  
Philipp Harter ◽  
Domenica Lorusso ◽  
Kathleen N Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Round Table ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
European Medicines Agency ◽  
First Line ◽  
Phase Iii Trials

Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the latest breakthrough in the management of newly diagnosed advanced ovarian cancer. The results of the SOLO-1 trial in 2018 led to European Medicines Agency and Food and Drug Administration approval of olaparib as first-line maintenance therapy in patients with BRCA1/2 mutation, establishing a new standard of care. Subsequently, the results of three phase III trials (PRIMA, PAOLA-1, VELIA) evaluating the use of first-line PARP inhibitors beyond patients with BRCA1/2 mutations and as combination strategies were presented in 2019, leading to the recent approval of maintenance niraparib irrespective of biomarker status and olaparib in combination with bevacizumab in homologous recombination deficiency-positive-associated advanced ovarian cancer. An ESMO Open - Cancer Horizons round-table expert panel discussed the four phase III trials of first-line PARP inhibitor therapy and how they are changing the clinical management of advanced ovarian cancer.

scholarly journals Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives – a review

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Sudeep Gupta ◽  
Shona Nag ◽  
Shyam Aggarwal ◽  
Amit Rauthan ◽  
Narayanankutty Warrier
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Epithelial Ovarian Cancer ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Optimal Timing ◽  
Special Focus ◽  
Future Perspectives ◽  
Current Therapies

Abstract Epithelial ovarian cancer (EOC) is usually diagnosed late at an advanced stage. Though EOC initially responds to treatment, the recurrence rate is pretty high. The efficacy of different targeted therapies reduces with each recurrence. Hence there is need of effective maintenance therapy in recurrent EOC. Recently, polyADP-ribose polymerase (PARP) inhibitors (PARPi) have been approved both for initial treatment of EOC and as its maintenance treatment. PARPi have also been found to act regardless of BRCA status or homologous recombination (HR) deficiency. Several trials testing PARPi early in maintenance therapy are in progress and their results will shed light on the optimal timing of maintenance therapy that gives the most benefit with least toxicity. Right patient selection for maintenance treatment is also a challenge. Hence, though PARPi are emerging as a promising maintenance treatment in recurrent EOC with prolongation of progression free survival (PFS), results from further trials and overall survival (OS) data from current trials are awaited to fulfill the gaps in understanding the role of this pathway in treatment of EOC. This review discusses the current therapies for EOC, challenges in the treatment of recurrent EOC, recent developments and trials in recurrent EOC maintenance with special focus on PARPi and future perspectives.

scholarly journals Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 24 ◽  
Author(s):  
Chin-Jui Wu ◽  
Vignesh Sundararajan ◽  
Bor-Ching Sheu ◽  
Ruby Yun-Ju Huang ◽  
Lin-Hung Wei
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Microenvironmental Factors ◽  
Therapeutic Opportunity ◽  
Molecular Therapeutic

Epithelial ovarian cancer (EOC) is the most lethal of all gynecologic malignancies. Despite advances in surgical and chemotherapeutic options, most patients with advanced EOC have a relapse within three years of diagnosis. Unfortunately, recurrent disease is generally not curable. Recent advances in maintenance therapy with anti-angiogenic agents or Poly ADP-ribose polymerase (PARP) inhibitors provided a substantial benefit concerning progression-free survival among certain women with advanced EOC. However, effective treatment options remain limited in most recurrent cases. Therefore, validated novel molecular therapeutic targets remain urgently needed in the management of EOC. Signal transducer and activator of transcription-3 (STAT3) and STAT5 are aberrantly activated through tyrosine phosphorylation in a wide variety of cancer types, including EOC. Extrinsic tumor microenvironmental factors in EOC, such as inflammatory cytokines, growth factors, hormones, and oxidative stress, can activate STAT3 and STAT5 through different mechanisms. Persistently activated STAT3 and, to some extent, STAT5 increase EOC tumor cell proliferation, survival, self-renewal, angiogenesis, metastasis, and chemoresistance while suppressing anti-tumor immunity. By doing so, the STAT3 and STAT5 activation in EOC controls properties of both tumor cells and their microenvironment, driving multiple distinct functions during EOC progression. Clinically, increasing evidence indicates that the activation of the STAT3/STAT5 pathway has significant correlation with reduced survival of recurrent EOC, suggesting the importance of STAT3/STAT5 as potential therapeutic targets for cancer therapy. This review summarizes the distinct role of STAT3 and STAT5 activities in the progression of EOC and discusses the emerging therapies specifically targeting STAT3 and STAT5 signaling in this disease setting.

scholarly journals The Treatment of Clear Cell Ovarian Cancer with the Poly(ADP- Ribose) Polymerase (PARP1) Inhibitors (AG14361,Veliparib,Olaparib) as Chemosensitizers

2020 ◽  
Author(s):  
Joseph Angel de Soto
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Clear Cell ◽  
Ovarian Cancer Cell ◽  
Adenosine Diphosphate ◽  
Cancer Cell Lines ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Ovarian Cancer Cell Lines

AbstractIntroductionMost of those who get ovarian cancer will die from this cancer. Of the major types of ovarian cancer clear cell carcinoma is the most aggressive and chemoresistant type of epithelial ovarian cancer. Here the sensitivity of clear cell ovarian carcinoma to poly adenosine diphosphate [ADP-ribose] polymerase (PARP) inhibitors is tested.MethodologyOvarian cancer cell lines were treated with the PARP inhibitors AG14361, Veliparib, or Olaparib alone or in combination with cisplatin, carboplatinum, doxorubicin, 5-fluorouracil (5-FU), gemcitabine and paclitaxel for 72 hours. The IC50 concentrations were calculated. Each experiment was replicated 10 times.ResultsAs single agents the PARP inhibition of ovarian cancer among serous, endometroid and clear cell ovarian cancer cell lines was similar. Clear cell ovarian cancer seemed particularly susceptible to chemo-sensitization by PARP inhibitors with paclitaxel, 5-FU, carboplatin, doxorubicin and/or cisplatin. Antagonism was seen with gemcitabine.ConclusionPARP inhibitors are exceptional chemosensitizers of clear cell ovarian cancer to treatment with most standard chemotherapy agents.

scholarly journals The latest first-line treatment options for ovarian cancer: focus on maintenance therapy

2020 ◽  
pp. 62-68
Author(s):  
A. A. Rumyantsev
Keyword(s):  
Ovarian Cancer ◽  
Comparative Analysis ◽  
Disease Progression ◽  
Treatment Options ◽  
Advanced Ovarian Cancer ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Published Data ◽  
Outpatient Basis ◽  
First Line

Ovarian cancer is one of the leading causes of death from gynecologic cancers in Russia: in 2018, 7616 women died from this disease and the proportion of patients who is under observation for 5 years or more was only 3.4%, which probably indicates very low 5-year survival. At the same time, there was is a tremendous paradigm shift in the treatment of BRCA-associated ovarian cancer. A number of large phase III trials have been published on the use of PARP inhibitors in this subtype of the disease. Their results demonstrated a marked reduction in the risk of disease progression or death with PARP inhibitors after first-line therapy for advanced ovarian cancer. Here we present a comparative analysis of the efficacy of various PARP inhibitors in BRCA-associated ovarian cancer. The relative risk reduction in disease progression or death for olaparib, niraparib and veliparib was 70%, 60% and 56%, respectively and advantage of using these drugs noted in all patient subgroups. Comparative analysis of the safety of various PARP inhibitors was carried out as well, the risks of developing various toxicity were assessed. Based on a comparison of published data on their safety profile, it was concluded that olaparib is the safest drug of this class, especially in the context of therapy on an outpatient basis. Possible ways to optimize the use of PARP inhibitors in disseminated ovarian cancer have been analyzed.

scholarly journals PARP Inhibitors in Ovarian Cancer: The Route to “Ithaca”

Diagnostics ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 55 ◽  
Author(s):  
Boussios ◽  
Karathanasi ◽  
Cooke ◽  
Neille ◽  
Sadauskaite ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Current Evidence ◽  
Repair Pathway ◽  
Significant Efficacy

Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Early studies have shown significant efficacy for PARP inhibitors in patients with germline breast related cancer antigens 1 and 2 (BRCA1/2) mutations. It has also become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this treatment. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The choice of which PARP inhibitor is mainly based upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of patients most likely to benefit from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The aim of this review is to describe the current evidence for PARP inhibitors in ovarian cancer, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolution of resistance.

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