373 Systematic literature review of efficacy and safety of first-line maintenance therapy trials in advanced ovarian cancer

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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Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2014.55.7348 ◽

2014 ◽

Vol 32 (30) ◽

pp. 3374-3382 ◽

Cited By ~ 199

Author(s):

Andreas du Bois ◽

Anne Floquet ◽

Jae-Weon Kim ◽

Joern Rau ◽

Josep M. del Campo ◽

...

Keyword(s):

Ovarian Cancer ◽

Growth Factor ◽

Adverse Events ◽

Maintenance Therapy ◽

Growth Factor Receptor ◽

Advanced Ovarian Cancer ◽

Progression Free Survival ◽

First Line ◽

Free Survival ◽

Line Chemotherapy

PurposePazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Patients and MethodsNine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.ResultsMaintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).ConclusionPazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).

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Successful maintenance therapy with apatinib inplatinum-resistant advanced ovarian cancer and literature review

Cancer Biology & Therapy ◽

10.1080/15384047.2018.1491500 ◽

2018 ◽

Vol 19 (12) ◽

pp. 1088-1092 ◽

Cited By ~ 5

Author(s):

Min Jin ◽

Jun Cai ◽

Xuan Wang ◽

Tao Zhang ◽

Yingchao Zhao

Keyword(s):

Ovarian Cancer ◽

Literature Review ◽

Maintenance Therapy ◽

Advanced Ovarian Cancer

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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.2020.39.28_suppl.294 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 294-294

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

294 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 6–9 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 record–derived 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, 0.16–0.59) than pts with BRCA mutation. Pts treated in 2018 (OR: 2.73; 95% CI, 1.25–5.98) and 2019 (OR: 8.78; 95% CI, 4.15–18.55) 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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Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer

Targeted Oncology ◽

10.1007/s11523-021-00842-1 ◽

2021 ◽

Author(s):

Julia Paik

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Advanced Ovarian Cancer ◽

First Line

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PAOLA-1: An ENGOT/GCIG phase III trial of olaparib versus placebo combined with bevacizumab as maintenance treatment in patients with advanced ovarian cancer following first-line platinum-based chemotherapy plus bevacizumab.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.tps5605 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. TPS5605-TPS5605 ◽

Cited By ~ 2

Author(s):

Isabelle Laure Ray-Coquard ◽

Philipp Harter ◽

Antonio Gonzalez Martin ◽

Claire Cropet ◽

Sandro Pignata ◽

...

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Maintenance Treatment ◽

Advanced Ovarian Cancer ◽

Chemotherapeutic Agents ◽

Phase Iii ◽

Brca Testing ◽

First Line ◽

Platinum Based Chemotherapy ◽

The Eu

TPS5605 Background: Olaparib (Lynparza) is an oral PARP inhibitor indicated in the EU for the maintenance treatment of patients (pts) with platinum-sensitive relapsed BRCA-mutated high grade serous ovarian cancer (HGSOC). Bevacizumab is an anti-VEGF monoclonal antibody indicated in the EU in first line or relapse for the treatment of OC in combination with specific chemotherapeutic agents. Bevacizumab treatment is associated with increasing hypoxia-induced homologous recombination repair deficiencies in tumor cells, and is hypothesized to increase ovarian tumor sensitivity to olaparib. Methods: PAOLA-1 (ENGOT-ov25) is a randomized, placebo-controlled trial evaluating the efficacy and safety of olaparib (tablet formulation) in pts with advanced HGSOC receiving bevacizumab maintenance therapy. Eligible pts are those in complete or partial response following first-line platinum chemotherapy plus bevacizumab, and for whom bevacizumab maintenance therapy is planned. Approximately 762 European and 24 Japanese pts will be randomized 2:1 to olaparib 300 mg twice daily or placebo for up to 24 months. All pts will receive standard maintenance care of bevacizumab (15 mg/kg every three weeks) for up to 15 months. Primary objective: PFS1 according to RECIST 1.1 Secondary objectives: PFS2, OS, Safety, PRO/QoL, TFST, TSST All pts will undergo tumor BRCA testing prior to randomization. Central BRCA testing (tumor) will be performed in five screening platforms in France. Tumor BRCA test results have to be available within two months of sample provision. PFS will be evaluated using a log-rank test stratified by response to first-line treatment and BRCA mutation status. Treatment effect hazard ratio of 0.7 is expected and final PFS1 analysis will be performed after 372 events. The first pt from eight ENGOT groups plus Japan (10 participating countries) was randomized in July 2015. As of 31 January 2017, 549 pts have been randomized. The median period between the provision of a tumor sample and returned BRCA test result is 40 days. Accrual is expected to be complete before July 2017. Clinical trial information: NCT02477644.

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