Progression after discontinuation of bevacizumab in the first-line treatment of ovarian cancer
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PROVIDER: S-EPMC10061489 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundCurrently, in Belgium, bevacizumab is reimbursed for ovarian cancer patients, based on a contract between the Minister and the manufacturer including confidential agreements. This reimbursement will be re-evaluated in 2018.ObjectiveTo support the reimbursement reassessment by calculating the cost-effectiveness of bevacizumab: (1) in addition to first-line chemotherapy; (2) in the treatment of recurrent ovarian cancer (platinum-sensitive or platinum-resistant).MethodsA health economic model has been developed for the Belgian situation according to the Belgian guidelines for economic evaluations. The lifetime Markov model was set up from the perspective of the health care payer (government and patient), including direct healthcare related costs. Results are expressed as the extra costs per quality-adjusted life year (QALY). Calculations were based on results of four international trials. Both probabilistic and one-way sensitivity analyses were performed.ResultsIncremental cost-effectiveness ratios (ICERs) of first-line bevacizumab are on average 158 000/QALY (GOG-0218 trial) and 443 000/QALY (ICON7 trial). The most favourable scenario is based on the stage IV subgroup of the GOG-0218 trial (€52 000/QALY). Since subgroup findings are often exploratory and require confirmatory studies, results of the economic evaluation based on this subgroup analysis should be considered with caution. For second-line bevacizumab, ICERs are on average €587 000/QALY (OCEANS trial) and €172 000/QALY (AURELIA trial). Sensitivity analysis shows that results are most sensitive to the price of bevacizumab.ConclusionFrom a health economic perspective, ICERs of bevacizumab are relatively high. The most favourable results are found for first-line treatment of stage IV ovarian cancer patients. Price reductions have a major impact on the estimated ICERs. It is recommended to take these findings into account when re-evaluating the reimbursement of bevacizumab in ovarian cancer.
| S-EPMC5891000 | biostudies-literature
Project description:ObjectiveDuring clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca.MethodsA panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab.ResultsThe subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training.ConclusionsThis expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.
| S-EPMC4399624 | biostudies-literature
Project description:Introduction: Bevacizumab-containing therapy is considered a standard-of-care front-line option for stage IIIB-IV ovarian cancer based on results of randomized phase 3 trials. The multicenter non-interventional ENCOURAGE prospective cohort study assessed treatment administration and outcomes in the French real-world setting. Patients and Methods: Eligible patients were aged ≥ 18 years with planned bevacizumab-containing therapy for newly diagnosed ovarian cancer. The primary objective was to assess the safety profile of front-line bevacizumab in routine clinical practice; secondary objectives were to describe patient characteristics, indications/contraindications for bevacizumab, treatment regimens and co-medications, follow-up and monitoring, progression-free survival, and treatment at recurrence. In this non-interventional study, treatment was administered as chosen by the investigator and participation in the trial had no influence on the management of the disease. Results: Of 1,290 patients screened between April 2013 and February 2015, 468 were eligible. Most patients (86%) received bevacizumab 15 mg/kg every 3 weeks or equivalent, typically with carboplatin (99%) and paclitaxel (98%). The median duration of bevacizumab was 12.2 (range 0-28, interquartile range 6.9-14.9) months; 8% of patients discontinued bevacizumab because of toxicity. The most common adverse events were hypertension (38% of patients), fatigue (35%), and bleeding (32%). There were no treatment-related deaths. Most physicians (90%) reported blood pressure measurement immediately before each bevacizumab infusion and almost all (97%) reported monitoring for proteinuria before each bevacizumab infusion. Median progression-free survival was 17.4 (95% CI, 16.4-19.1) months. The 3-year overall survival rate was 62% (95% CI, 58-67%). The most commonly administered chemotherapies at recurrence were carboplatin and pegylated liposomal doxorubicin. Discussion: Clinical outcomes and tolerability with bevacizumab in this real-life setting are consistent with randomized trial results, notwithstanding differences in the treated patient population and treatment schedule. Clinical Trial Registration:ClinicalTrials.gov, Identifier NCT01832415.
| S-EPMC8489574 | biostudies-literature
Project description:Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a number of different backbone chemotherapy regimens, and its widespread use has introduced several important questions regarding the selection and optimization of bevacizumab-based treatment regimens, its use in various patient populations, and the identification of associated adverse events. This review discusses the results of several phase II and phase III clinical trials, as well as large observational studies, to address the use of bevacizumab in the treatment of patients with mCRC in the first-line setting.
| S-EPMC3336830 | biostudies-other
Project description:BackgroundIn the PAOLA-1 trial, olaparib plus bevacizumab demonstrated significant clinical benefit following partial or complete response to platinum-based chemotherapy in homologous recombination deficiency (HRD)-positive ovarian cancer. Our study evaluated the cost effectiveness of olaparib plus bevacizumab compared with bevacizumab alone as a maintenance treatment for women in this population.MethodsOur model was a cohort-level partitioned survival model with a lifetime horizon from a US healthcare system perspective. Its four health states were progression-free, post first progression, post second progression, and death, modeled using time to first progression (PFS1), second progression (PFS2), and overall survival (OS) from PAOLA-1. We modeled PFS1 through mixture survival modeling, and PFS2 and OS by fitting standard parametric models. Time-on-treatment was sourced directly from PAOLA-1, with treatment capped at 24 months for olaparib and 15 months for bevacizumab. Costs included drug acquisition and administration, adverse events, disease management, biomarker testing, and subsequent treatments. Deterministic and probabilistic sensitivity analyses tested the results.ResultsCompared with bevacizumab alone, olaparib plus bevacizumab increased quality-adjusted life-years (QALYs; +2.89) and life-years (LYs; +3.43) at an incremental cost of $164,209, leading to an incremental cost-effectiveness ratio of $56,863 per QALY. Olaparib plus bevacizumab had a 97.0% probability of being cost effective compared with bevacizumab alone at a willingness-to-pay threshold of $100,000 per QALY.ConclusionThe addition of olaparib to bevacizumab led to clinically significant increases in progression-free survival, resulting in substantial predicted LYs and QALYs gained, while being cost effective in the maintenance treatment of advanced ovarian cancer with HRD in the US.
| S-EPMC9596645 | biostudies-literature
Project description:BackgroundThe ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab.MethodsThe subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis.ResultsSixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0-1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46-1.34], p = 0.373, adjusted HR: 0.87 [0.41-1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38-1.12], p = 0.125, adjusted HR 0.53 [0.27-1.07], p = 0.078).ConclusionIn mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.
| S-EPMC8555183 | biostudies-literature
Project description:IntroductionThe non-interventional study (NIS) KORALLE evaluated the effectiveness and safety of bevacizumab in patients with metastatic colorectal carcinoma (mCRC) treated with bevacizumab in combination with fluoropyrimidine-based chemotherapy in the first-line setting and beyond first progression in routine clinical practice.MethodsThis prospective, multicenter NIS observed adult patients with mCRC who started first-line bevacizumab therapy. The planned maximum duration of observation per patient was 21 months. The primary effectiveness variable was progression-free survival in the first-line therapy setting (PFS-1). Secondary effectiveness variables included PFS after first progression as well as overall survival and overall response rate. All analyses were carried out descriptively for the full analysis population set (FAS). Effectiveness analyses were also assessed for predefined subgroups based on therapy goals.ResultsBetween December 2012 and July 2016, 2,429 eligible patients were observed at 314 sites in Germany. In the first-line setting in the FAS, the median PFS-1 was 10.3 months (95% CI: 9.9; 10.8), the median overall survival was 16.9 months (95% CI: 16.3; 17.5), and the overall response rate (ORR-1) was 44.2% (95% CI: 41.6%; 46.8%). Effectiveness results of all subgroups were similar to the FAS. Overall, 80.9% of patients experienced any adverse events, 36.6% of patients experienced serious adverse events, and 8.8% of patients experienced fatal adverse events.ConclusionThe NIS KORALLE provided broad real-world evidence on effectiveness and safety of bevacizumab. Despite different treatment intentions, the combination of bevacizumab plus fluoropyrimidine-based chemotherapy was similarly effective in all subgroups in routine clinical practice. The safety information reported in this study is consistent with the known safety profile of bevacizumab.
| S-EPMC9677830 | biostudies-literature
Project description: Not available
| S-EPMC5898654 | biostudies-literature
Project description:To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression. Intensity and extent of staining were combined into a semi-quantitative visual grading system (H score) which was related to clinicopathological characteristics of cases and the clinical outcome of patients by univariate and multivariate Cox regression models. ADAM17 immunostaining was detected in most samples, mainly localized in the tumor cells, with variable intensity across the cohort. Kaplan-Meier survival curves, generated according to the best cut-off value for the ADAM17 H score, showed that high ADAM17 expression was associated with worse prognosis for PFS and OS. However, after the application of a shrinkage procedure to adjust for overfitting hazard ratio estimates, the ADAM17 value as prognostic factor was lost. As subgroup analysis suggested that ADAM17 expression could be prognostically relevant in cases with no residual disease at baseline, further studies in this patient category may be worth planning.
| S-EPMC9498026 | biostudies-literature
Project description:BACKGROUND: The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. METHODS: Treatment consisted of capecitabine 1250 mg m(-2) (or 950 mg m(-2) for patients with a creatinine clearance of 30-50 ml min(-1)) twice daily on days 1-14 and bevacizumab (7.5 mg kg(-1)) on day 1 every 3 weeks. RESULTS: A total of 59 patients aged >or=70 years with mCRC were enrolled. In an intention-to-treat analysis, the overall response rate was 34%, with 71% of patients achieving disease control. Median progression-free survival and overall survival were 10.8 months and 18 months, respectively. In all, 32 patients (54%) had grade 3/4 adverse events (AEs), the most common being hand-foot syndrome (19%), diarrhoea (9%) and deep venous thrombosis (7%). Four patients died because of treatment-related AEs. A relationship was detected between creatinine clearance <or=50 ml min(-1) and the development of non-bevacizumab-related grade 3/4 AEs. The incidence of bevacizumab-associated AEs (hypertension, thromboembolic events and proteinuria) was consistent with that of previous reports in elderly patients. CONCLUSION: Bevacizumab combined with capecitabine represents a valid therapeutic alternative in elderly patients considered to be unsuitable for receiving polychemotherapy.
| S-EPMC2869164 | biostudies-other