PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta‐analysis

Abstract Purpose To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics. Methods We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer. Results We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29–0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67–1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events). Conclusions PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.

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Phase III PAOLA-1/ENGOT-ov25 trial: Olaparib plus bevacizumab (bev) as maintenance therapy in patients (pts) with newly diagnosed, advanced ovarian cancer (OC) treated with platinum-based chemotherapy (PCh) plus bev

10.1055/s-0040-1717197 ◽

2020 ◽

Author(s):

A Schnelzer ◽

P Harter ◽

J Sehouli ◽

U Canzler ◽

F Marmé ◽

...

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Advanced Ovarian Cancer ◽

Phase Iii ◽

Newly Diagnosed ◽

Platinum Based Chemotherapy

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Real-world patterns and predictors of first-line maintenance use among patients with newly diagnosed advanced ovarian cancer: Is there an opportunity for change?

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18710 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18710-e18710

Author(s):

Jinan Liu ◽

Premal H. Thaker ◽

Janvi Sah ◽

Eric M. Maiese ◽

Oscar Bee ◽

...

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Real World ◽

Index Date ◽

Advanced Ovarian Cancer ◽

Newly Diagnosed ◽

First Line ◽

Receive Maintenance Therapy ◽

Platinum Based Chemotherapy ◽

To Receive

e18710 Background: With the advent of poly(ADP-ribose) polymerase inhibitors (PARPi), options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US. This study described the use of 1L maintenance and assessed predictors of 1L maintenance use among PARPi-eligible patients (pts) with OC in a real-world setting. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV epithelial OC who received 69 cycles of 1L platinum-based chemotherapy (PBC) and primary or interval debulking surgery following neoadjuvant chemotherapy between Jan 1, 2016, and Feb 29, 2020, from the nationwide Flatiron Health electronic health recordderived deidentified database. The end of the last cycle of 1L PBC was defined as the index date. Those pts who started second-line chemotherapy within 2 months of the index date were excluded. Logistic regression was used to analyze variables with regard to 1L maintenance use. Results: In total, 463 pts were included; 21% received maintenance therapy, 79% received active surveillance. Baseline characteristics are shown in the table. Overall maintenance therapy use increased over the study period, from 7.7% to 37.7%. Pts with BRCA wild type were significantly less likely to receive maintenance therapy (odds ratio [OR]: 0.30; 95% CI, 0.160.59) than pts with BRCA mutation. Pts treated in 2018 (OR: 2.73; 95% CI, 1.255.98) and 2019 (OR: 8.78; 95% CI, 4.1518.55) were significantly more likely to receive maintenance therapy than pts treated in 2017. Age, race, practice type, ECOG score, and residual disease status were not significant predictors of 1L maintenance use. Conclusions: Nearly 40% of pts with advanced stage OC received upfront maintenance therapy with an increasing trend over time, particularly in those with biomarker guidance. Research is warranted toward addressing barriers to the appropriate use of maintenance therapy.[Table: see text]

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

ESMO Open ◽

10.1136/esmoopen-2020-001110 ◽

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.

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Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis

Future Oncology ◽

10.2217/fon-2020-0057 ◽

2020 ◽

Vol 16 (10) ◽

pp. 585-596 ◽

Cited By ~ 3

Author(s):

Ezzeldin M Ibrahim ◽

Ahmed A Refae ◽

Ali M Bayer ◽

Emad R Sagr

Keyword(s):

Ovarian Cancer ◽

Randomized Clinical Trials ◽

Brca Mutation ◽

Meta Analysis ◽

Advanced Ovarian Cancer ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Newly Diagnosed ◽

Free Survival ◽

Polymerase Inhibitors

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39–0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.

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