Front‐line ovarian cancer maintenance therapy: PARP inhibitors for all?

2020 ◽  
Author(s):  
JL Berger
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Parp Inhibitors ◽  
Front Line

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.

Uptake of targeted therapy in clinical practice among US patients with ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18049-e18049
Author(s):  
John K. Chan ◽  
Larissa Meyer ◽  
Patricia Luhn ◽  
Carlos Flores ◽  
Lydie Bastiere-Truchot ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Parp Inhibitors ◽  
Brca Mutations ◽  
Platinum Sensitive ◽  
Level Data ◽  
Treatment Data ◽  
History Of ◽  
Combination Studies

e18049 Background: Since first approvals for targeted therapies (TTs) in ovarian cancer (OC) patients (pts) in 2014, FDA approvals for TTs including bevacizumab (bev) and PARP inhibitors (PARPis) continue to expand. Approval of front line (1L) indications for bevacizumab (all-comers) and maintenance olaparib (BRCA-mutated) occurred in 2018. Here we describe real-world trends in the use of these TTs. Methods: Data were analyzed from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database of patient-level data, curated via technology-enabled abstraction. We used descriptive statistics and significance tests to describe TT use in pts with OC. Results: We included 2975 treated OC pts diagnosed from 2011-18, with treatment data through 2019. Median follow-up was 32 months. 47% of OC pts received TT during follow-up, 12% of whom received TT during 1L. TTs were given as maintenance therapy in 54% of 1L and 37% of recurrent (2L+) OC pts. 40% of OC pts received bevacizumab anytime, 24% of whom received bevacizumab during 1L. Bevacizumab was given as maintenance therapy in 43% of 1L and 26% of recurrent OC pts. 20% of 2L and 17% of 3L bevacizumab-treated pts were platinum sensitive. From 2012-19, bevacizumab use changed biennially from 10% to 10% to 8% to 18% in FL (p < 0.001), 24% to 35% to 34% to 38% in 2L (p = 0.008), and 21% to 34% to 35% to 36% in 3L (p = 0.06). Corresponding changes in PARPis use were 0% to 0% to 5% to 13% in FL (p = 0.03), 0% to 1% to 11% to 23% in 2L (p = 0.09), and 0% to 3% to 10% to 20% in 3L (p = 0.02). TT use (ever vs. never during follow-up) was more common among pts with stage III-IV tumors (81% vs. 55%), serous histology (90% vs. 75%), history of BRCA (82% vs. 61%) or NGS (38% vs. 13%) testing, and BRCA mutations (21% vs. 33%) (p < 0.001 for all). Conclusions: Bevacizumab and PARPi use is expanding in 1L and 2L treatment; in 1L bevacizumab was more common than PARPis in 2019 (31% vs. 19%). These data reflect the evolving treatment landscape in 1L OC, which is expected to further evolve based on recent evidence from maintenance PARPi monotherapy and PARPi + bevacizumab combination studies. [Table: see text]

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.

Real-world clinical practice: Toxicities of maintenance PARP inhibitors in recurrent ovarian cancer—The Royal Marsden experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18770-e18770
Author(s):  
Zohra Ali ◽  
Laura Appadu ◽  
Ellen Kitetere ◽  
Julian Wampfler ◽  
Dorothy Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Practice ◽  
Maintenance Therapy ◽  
Real World ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Routine Clinical Practice ◽  
Phase Iii ◽  
Low Grade ◽  
Starting Dose

e18770 Background: Maintenance therapy with PARP inhibitors (PARPi) in recurrent high grade ovarian cancer is standard of care for patients who have responded to second or subsequent lines of platinum-based chemotherapy. The increased access to PARP inhibitors (Olaparib, Niraparib and Rucaparib) has provided the opportunity to explore the real-world toxicities in routine clinical practice, toxicity management and the consequent impact on maintenance therapy outcomes. Methods: Patients with relapsed ovarian cancer that received maintenance PARP inhibitor therapy in routine clinical practice between April 2015 and April 2020 were identified. Electronic patient records were reviewed retrospectively to retrieve details of any reported toxicities (occurring at any time during therapy) and their management. Data was entered into and analysed in a Microsoft Excel spreadsheet. Results: 99 patients who received second or subsequent line maintenance PARPi therapy were included (median age 63.6 years). 36% had a germline BRCA1/2 mutation, 6% had a somatic BRCA1/2 mutation and 58% were BRCA wild-type. 69% received 2nd line maintenance therapy; 22% and 9% received a maintenance PARP inhibitor following 3rd or 4+ line therapy respectively. 56% had not received previous maintenance therapy; 43% had received Bevacizumab. 48% patients commenced maintenance therapy at full dose. 13% of patients experienced no toxicities. 60% of patients experienced G1-2 toxicities, with 42% experiencing >2 episodes; most common toxicities were fatigue, nausea/vomiting and thrombocytopenia. 26% of patients experienced >G3 toxicity, with 9% experiencing >2 episodes, 4% of which were recurring toxicities; most common toxicities were hypertension, neutropenia and anaemia. 64% of patients developed toxicity within the first cycle of treatment; 39% had a dose interruption, 56% of which were < 2 weeks duration. 59% patients required a dose reduction from their starting dose due to toxicities. There was no significant difference in median PFS between patients who had been dose reduced compared to those who received full starting dose (p > 0.05). Conclusions: In keeping with phase III clinical trials, our real-world experience is that most PARPi toxicities are low grade and occur early in treatment. Toxicities can be effectively managed with brief dose interruptions and dose reductions, without adverse impact on survival outcomes.

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