scholarly journals Estimating long-term overall survival with olaparib as maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations

2021 ◽  
Vol 17 (3) ◽  
pp. 97-105
Author(s):  
N. A. Avxentyev ◽  
S. V. Khokhlova ◽  
M. Yu. Frolov ◽  
A. S. Makarov
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
First Line ◽  
Brca Mutations ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Line Chemotherapy

Background. According to randomized clinical trial SOLO1 olaparib statistically significantly improves progression-free survival versus placebo as a maintenance monotherapy in patients aged 18 and over with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy. As the data on overall survival (OS) in this trial remains interim it is still uncertain whether treatment with olaparib can provide any benefits in terms of OS.Objective: to evaluate a long-term OS for olaparib versus placebo as a maintenance monotherapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy.Materials and methods. A 10-year mathematic model of disease progression and survival on olaparib versus placebo was developed. Modelling was based on data on progression-free survival from SOLO1 trial and data on OS after platinum-sensitive and platinum-resistant relapses from OCEANS and AURELIA trials. Additionally, patients who haven’t been treated with olaparib after first-line therapy in base-case scenario were assumed to get olaparib as a second-line treatment after platinum-sensitive relapse; mortality modelling for these patients was based on data from SOLO2 trial.Results. Median OS for olaparib was 107 months versus 66 months for placebo. 46 % of patients treated with olaparib were alive by the end of 10-year modelling period, but only 28 % patients from the placebo group. Hazard ratio of death for olaparib versus placebo was 0.64 (95 % confidence interval 0.49–0.84). Probabilistic sensitivity analysis showed robustness of these results.Conclusion. Using olaparib as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response on first line chemotherapy, statistically significantly reduces risk of death by 36 %, compared to placebo.

Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

2014 ◽  
Vol 32 (30) ◽  
pp. 3374-3382 ◽  
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).

scholarly journals First-line treatment of advanced ovarian cancer: an expert update

2020 ◽  
Vol 48 (2-3) ◽  
pp. 77-84
Author(s):  
Branka Petrić-Miše ◽  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
New Drugs ◽  
Treatment Schedule ◽  
Line Treatment ◽  
First Line ◽  
Brca Mutations ◽  
Line Chemotherapy ◽  
First Line Treatment

Ovarian cancer is the fifth most common cause of death among malignant diseases in women in Europe. The standard treatment is cytoreductive surgery, followed by platinum-taxane based chemotherapy. In patients with advanced disease, a valid option is a neoadjuvant chemotherapy followed by interval debulking surgery. Despite the progress in primary treatment, almost 70% of the patients relapse. There is a significant need for better first-line treatment to avoid or delay relapse and improve ovarian cancer outcomes. The most significant change involves the changes in the treatment schedule and new drugs in first-line chemotherapy. Bevacizumab is approved in first-line treatment combined with carboplatin and paclitaxel as it improves progression-free survival (PFS) in patients with a higher risk of recurrence. After achieving the response to first-line chemotherapy, maintenance therapy with poly-adenosine-diphosphate-ribose-polymerase (PARP) inhibitors prolongs PFS in patients with homologous recombination deficiency (HRD). Patients with BRCA mutations obtain the most significant benefit.

Poly-(ADP-ribose) polymerase inhibitors: paradigm shift in the first-line treatment of newly diagnosed advanced ovarian cancer

2020 ◽  
Vol 21 (10) ◽  
pp. 721-727
Author(s):  
Fady Gh Haddad ◽  
Elias Karam ◽  
Elissar Moujaess ◽  
Hampig Raphael Kourie
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Excision Repair ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
First Line ◽  
Free Survival ◽  
Base Excision ◽  
Breast Cancer Gene

Debulking surgery associated with chemotherapy represent the backbone of ovarian cancer therapy. Adding bevacizumab has improved survival. Recently, PARP inhibitors were added in the first line as maintenance treatment for the patients who achieve a complete or partial response. These drugs act by blocking the activity of the PARP enzyme responsible for base-excision repair, and have shown positive responses when used for tumors lacking homologous recombination. Olaparib, niraparib and veliparib were evaluated and showed an increase in the duration of progression-free survival: 22.1 months (hazard ratio [HR] = 0.59), 13.8 (HR = 0.62) and 23.5 (HR = 0.68) with olaparib, niraparib and veliparib, respectively. This review describes the benefit of PARP inhibitors as maintenance therapy and discusses the efficacy according to breast cancer gene and homologous recombination status.

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

2020 ◽  
Vol 16 (10) ◽  
pp. 585-596 ◽  
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.

The safety and efficacy of weekly paclitaxel and cisplatin chemotherapy for patients with ovarian cancer who developed carboplatin hypersensitivity reaction in previous chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6058-6058
Author(s):  
Kyoko Nishikimi ◽  
Shinichi Tate ◽  
Ayumu Matsuoka ◽  
Makio Shozu
Keyword(s):  
Ovarian Cancer ◽  
Sodium Phosphate ◽  
Progression Free Survival ◽  
Weekly Paclitaxel ◽  
First Line ◽  
Peritoneal Carcinoma ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Platinum Sensitive ◽  
Carboplatin Hypersensitivity

6058 Background: Carboplatin (CBDCA) hypersensitivity reactions (HSR) often occur in patients with ovarian cancer. Once CBACA HSR occurs, it is difficult to use platinum even though the patients had platinum-sensitive disease and consequently the survival of the patients cannot be prolonged. We had administered weekly paclitaxel and cisplatin (CDDP) chemotherapy (wTP) for patients with ovarian cancer who developed CBDCA HSR in previous chemotherapy. We investigated the safety and efficacy of wTP. Methods: We investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed CBDCA HSR in previous chemotherapy (paclitaxel/CBDCA) at our institution between 2011 and 2019. After premedication was administered, paclitaxel and sequentially CDDP were administered as one hour infusion, respectively (paclitaxel 80 mg/m2, CDDP 25 mg/m2; 1, 8, 15 day/4 weeks). Results: The median cycle of the previous chemotherapy of CBDCA was 8 (interquartile range [IQR], 6–11). The grade of CBDCA HSR was 1 in 57 (66%), 2 in 26 (30%), and, 3 in 1 (1%) patient(s). WTP was administered for the first line in 21 (24%), second line in 35 (41%) and third or more line in 30 patients (34%). The median cycles of wTP administration was 4 (IQR, 3–7). We observed that severe CDDP HSR did not occur in any patients and 15 patients (17.4%, grade 1, 10 patients; grade 2, 5) developed CDDP HSR. All CDDP HSR were successfully managed with infusion interruption and Hydrocortisone Sodium Phosphate administration. There was no relation between the grade of CBDCA HSR in the previous chemotherapy and the rate of CDDP HSR (p = 0.363). Progression-free survival and overall survival after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95%Ci: 19.0–50.2), respectively. Conclusions: 71 patients (82%) who developed CBDCA HSR in previous chemotherapy were able to continue administration of wTP without CDDP HSR. WTP was safe and effective for the patients who developed CBDCA HSR. [Table: see text]

Phase III Trial of High-Dose Sequential Chemotherapy With Peripheral Blood Stem Cell Support Compared With Standard Dose Chemotherapy for First-Line Treatment of Advanced Ovarian Cancer: Intergroup Trial of the AGO-Ovar/AIO and EBMT

2007 ◽  
Vol 25 (27) ◽  
pp. 4187-4193 ◽  
Author(s):  
Volker Möbus ◽  
Hannes Wandt ◽  
Norbert Frickhofen ◽  
Carmelo Bengala ◽  
Kim Champion ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peripheral Blood Stem Cell ◽  
Standard Dose ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
High Dose ◽  
First Line ◽  
Sequential Chemotherapy ◽  
Free Survival ◽  
First Line Treatment

PurposeAlthough ovarian cancer is one of the most chemotherapy-sensitive solid tumors, cure after radical surgery and chemotherapy is uncommon. A randomized trial comparing high-dose sequential chemotherapy with peripheral blood stem cell (PBSC) support with platinum-based combination chemotherapy was conducted to investigate whether dose-intensification improves outcome.Patients and MethodsOne hundred forty-nine patients with untreated ovarian cancer were randomly assigned after debulking surgery to receive standard combination chemotherapy or sequential high-dose (HD) treatment with two cycles of cyclophosphamide and paclitaxel followed by three cycles of HD carboplatin and paclitaxel with PBSC support. HD melphalan was added to the final cycle. The median age was 50 years (range, 20 to 65 years) and International Federation of Gynecology and Obstetrics stage was IIb/IIc in 4%, III in 78%, and IV in 17%.ResultsSeventy-six percent of patients received all five cycles in the HD arm and the main toxicities were neuro-/ototoxicity, gastrointestinal toxicity, and infection and one death from hemorrhagic shock. After a median follow-up of 38 months, the progression-free survival was 20.5 months in the standard arm and 29.6 months in the HD arm (hazard ratio [HR], 0.84; 95% CI, 0.56 to 1.26; P, .40). Median overall survival (OS) was 62.8 months in the standard arm and 54.4 months in the HD arm (HR, 1.17; 95% CI, 0.71 to 1.94; P, .54).ConclusionThis is the first randomized trial comparing sequential HD versus standard dose chemotherapy in first-line treatment of patients with advanced ovarian cancer. We observed no statistically significant difference in progression-free survival or OS and conclude that HD chemotherapy does not appear to be superior to conventional dose chemotherapy.

Long-term follow-up confirms a survival advantage of the paclitaxel–cisplatin regimen over the cyclophosphamide–cisplatin combination in advanced ovarian cancer

2003 ◽  
Vol 13 (Suppl 2) ◽  
pp. 144-148 ◽  
Author(s):  
M. J. Piccart ◽  
K. Bertelsen ◽  
G. Stuart ◽  
J. Cassidy ◽  
C. Mangioni ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Randomized Clinical Trials ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Clinical Response Rate ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Clinically Significant

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European–Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin–paclitaxel regimen over cisplatin–cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

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