LBA33 Maintenance olaparib plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced high‐grade ovarian carcinoma (HGOC): Final analysis of second progression-free survival (PFS2) in the phase III PAOLA-1/ENGOT-ov25 trial

Martín, A. González; Tazi, Youssef; Heitz, Florian; Montané, Laure; Gargiulo, Piera; Berger, Regina; Yonemori, Kan; Vergote, Ignace; Bologna, Alessandra; Mäenpää, Johanna; Costan, Cristina; Canzler, Ulrich; Zamagni, Claudio; Guerra-Alia, E; Levaché, Charles-Briac; Marmé, Frederik; Kalbacher, Elsa; Gregorio, Nikolaus de; Dohollou, N.

doi:10.1016/j.annonc.2020.08.2263

Cited by 10 publications

(5 citation statements)

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“…In predefined subgroup analyses, PFS findings favoured olaparib plus bevacizumab over placebo plus bevacizumab in patients with HRD-positive tumours (defined by tumour HRD score ≥ 42 or a tumour BRCA mutation) [20].…”

Section: Combination Therapy With Bevacizumabmentioning

confidence: 97%

“…The TFST was improved by 41% with olaparib plus bevacizumab relative to placebo plus bevacizumab (Table 2) [14]. At the final analysis of second PFS (occurring a year after the initial interim analysis), second PFS was significantly improved with olaparib plus bevacizumab (Table 2) as was the TSST (median 38.2 months vs 31.5 months; HR 0.75, 95% CI 0.64-0.95; p = 0.0115) [abstract] [20].…”

Section: Combination Therapy With Bevacizumabmentioning

confidence: 99%

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Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer

Paik

2021

Targ Oncol

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Olaparib (Lynparza ® ) is a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor approved for first-line maintenance treatment in adults with advanced ovarian cancer who are in complete or partial response to first-line, platinum-based chemotherapy. Originally approved as monotherapy, olaparib is also approved to be administered in combination with bevacizumab in patients whose cancer is associated with homologous recombination deficiency (HRD), defined by either a BRCA1/2 mutation and/or genomic instability. In phase III trials, olaparib monotherapy significantly improved progressionfree survival (PFS) relative to placebo (SOLO-1), as did olaparib plus bevacizumab relative to placebo plus bevacizumab (PAOLA-1), in patients with advanced ovarian cancer who had responded to platinum-based chemotherapy. In PAOLA-1, improvements in PFS with olaparib plus bevacizumab were not seen in patients with HRD-negative tumours relative to placebo plus bevacizumab. Both olaparib monotherapy and olaparib in combination with bevacizumab had generally manageable tolerability profiles. Olaparib, alone or in combination with bevacizumab, is a useful option for the first-line maintenance treatment of adults with HRD-positive, advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy. Plain Language SummaryOral olaparib (Lynparza ® ) was originally approved as monotherapy for the first-line maintenance treatment of adults with advanced high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who responded to first-line, platinum-based chemotherapy. Olaparib is also approved to be used in combination with bevacizumab in patients whose cancer is associated with homologous recombination deficiency (HRD), which is characterized by BRCA1/2 mutations or genomic instability. Olaparib reduced the risk of disease progression or death in patients who had received platinum-based chemotherapy without bevacizumab (when olaparib was given as monotherapy) and with bevacizumab (when olaparib was given with bevacizumab). However, this reduction was not seen in patients with HRD-negative tumours who were treated with olaparib plus bevacizumab compared with placebo plus bevacizumab. Both olaparib monotherapy and olaparib in combination with bevacizumab had generally manageable tolerability profiles. Olaparib, alone or in combination with bevacizumab, is a useful option for the first-line maintenance treatment of adults with HRD-positive, advanced ovarian cancer who responded to first-line, platinumbased chemotherapy.

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Section: Combination Therapy With Bevacizumabmentioning

confidence: 97%

Section: Combination Therapy With Bevacizumabmentioning

confidence: 99%

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer

Paik

2021

Targ Oncol

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“…The ever-reached rate of PFS under frontline PARPi questioned the possibility that PARPi added to standard optimal treatment (complete cytoreductive surgery and adjuvant chemotherapy) could contribute to cure a proportion of HGOC patients. Beyond BRCA-mutated patients in SOLO1, PRIMA and PAOLA-1, the clinically lower-risk (absence of residual disease at primary debulking surgery) HRD population in PAOLA-1 who received a maintenance therapy combining bevacizumab + olaparib reached 90% progression-free rate at 2 years [51,52]. The longterm benefit of this strategy does not seem to fall after the completion of the 2-years maintenance.…”

Section: New Expectations From Parpi Maintenancementioning

confidence: 98%

“…Although OS data are not mature yet, there may be a remnant effect of frontline strategy since PFS2 (survival on subsequent therapy following progression on front-line therapy) was significantly longer in the PARPi arm (±bevacizumab) over placebo arm (±bevacizumab) in SOLO1, PRIMA and PAOLA-1 , knowing some control-arm patients had a cross over to PARPi (36% in PAOLA-1) [52][53][54]. Recently, the PFS2 of the HRD population of PAOLA-1 trial was reported to be significantly prolonged in all stages [55].…”

Section: Emerging Questions Of Frontline Maintenancementioning

confidence: 99%

PARP-inhibitors in epithelial ovarian cancer: Actual positioning and future expectations

Vanacker

Harter

Labidi-Galy

et al. 2021

Cancer Treatment Reviews

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“…The biggest benefit gained was in the BRCA-mutant cohort where the median PFS has not been reached versus 45 months for placebo and BV (HR 0.53,. The next best group to benefit was the HRD cohort at 50.3 versus 35.3 months for placebo (HR 0.56, CI 0.41-0.77) comparatively the HRD negative cohort performed the worst at 24.4 vs. 26.4 months (HR 1.04, CI 0.77-1.42) (Martín et al, 2020). The combination of PARPi and BV offers a benefit in extending PFS, especially in BRCA-mutant and HRD HGSOC, however the magnitude of clinical benefit in HR proficient cohorts is less clear.…”

Section: Anti-angiogenics and Parpimentioning

confidence: 99%

Improving PARP inhibitor efficacy in high-grade serous ovarian carcinoma: A focus on the immune system

et al. 2022

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High-grade serous ovarian carcinoma (HGSOC) is a genomically unstable malignancy responsible for over 70% of all deaths due to ovarian cancer. With roughly 50% of all HGSOC harboring defects in the homologous recombination (HR) DNA repair pathway (e.g., BRCA1/2 mutations), the introduction of poly ADP-ribose polymerase inhibitors (PARPi) has dramatically improved outcomes for women with HR defective HGSOC. By blocking the repair of single-stranded DNA damage in cancer cells already lacking high-fidelity HR pathways, PARPi causes the accumulation of double-stranded DNA breaks, leading to cell death. Thus, this synthetic lethality results in PARPi selectively targeting cancer cells, resulting in impressive efficacy. Despite this, resistance to PARPi commonly develops through diverse mechanisms, such as the acquisition of secondary BRCA1/2 mutations. Perhaps less well documented is that PARPi can impact both the tumour microenvironment and the immune response, through upregulation of the stimulator of interferon genes (STING) pathway, upregulation of immune checkpoints such as PD-L1, and by stimulating the production of pro-inflammatory cytokines. Whilst targeted immunotherapies have not yet found their place in the clinic for HGSOC, the evidence above, as well as ongoing studies exploring the synergistic effects of PARPi with immune agents, including immune checkpoint inhibitors, suggests potential for targeting the immune response in HGSOC. Additionally, combining PARPi with epigenetic-modulating drugs may improve PARPi efficacy, by inducing a BRCA-defective phenotype to sensitise resistant cancer cells to PARPi. Finally, invigorating an immune response during PARPi therapy may engage anti-cancer immune responses that potentiate efficacy and mitigate the development of PARPi resistance. Here, we will review the emerging PARPi literature with a focus on PARPi effects on the immune response in HGSOC, as well as the potential of epigenetic combination therapies. We highlight the potential of transforming HGSOC from a lethal to a chronic disease and increasing the likelihood of cure.

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LBA33 Maintenance olaparib plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced high‐grade ovarian carcinoma (HGOC): Final analysis of second progression-free survival (PFS2) in the phase III PAOLA-1/ENGOT-ov25 trial

Cited by 10 publications

References 0 publications

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer

PARP-inhibitors in epithelial ovarian cancer: Actual positioning and future expectations

Improving PARP inhibitor efficacy in high-grade serous ovarian carcinoma: A focus on the immune system

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