Bevacizumab in recurrent, persistent, or advanced stage carcinoma of the cervix: is it cost-effective?
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ABSTRACT:
SUBMITTER: Phippen NT
PROVIDER: S-EPMC5553065 | biostudies-other | 2015 Jan
REPOSITORIES: biostudies-other
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Project description:Uterine cervix cancers pose therapeutic challenges because of an overactive ribonucleotide reductase, which provides on-demand deoxyribonucleotides for DNA replication or for a DNA damage repair response. Ribonucleotide reductase overactivity bestows cancer cell resistance to the effects of radiotherapy and chemotherapy used to treat disease; but nevertheless, this same biologic overexpression provides opportune vulnerabilities relatively specific to uterine cervix cancers for new therapeutic strategies to take advantage. The discovery of human epidermal growth factor receptor 2 (ErbB2 or HER2) overexpression on metastatic uterine cervix cancer cells provides an opportunity for clinical trials of targeted radiopharmaceuticals in combination with DNA damage response modifying drugs. The National Cancer Institute's clinical trial infrastructure and its experimental therapeutics portfolio can now offer clinical trial evaluation of molecularly-targeted and tolerated radiopharmaceutical-drug combinations for women with persistent or recurrent metastatic uterine cervix cancer. This article discusses the current thinking of the National Cancer Institute in regard to attractive radiopharmaceutical strategies for this disease and others.
| S-EPMC6607970 | biostudies-literature
Project description:PurposeTo estimate the antitumor activity of pemetrexed and cisplatin with objective tumor response (partial and complete) in patients with advanced, persistent, or recurrent carcinoma of the cervix and to determine the nature and degree of toxicity of this regimen. Secondarily, this study will determine the effects of this regimen on progression-free survival and overall survival.Patients and methodsEligible, consenting patients received pemetrexed 500 mg/m(2) and cisplatin 50 mg/m(2) intravenously repeated every 21 days until disease progression or adverse events prohibited further therapy. Patients received no prior therapeutic chemotherapy, except when administered concurrently with primary radiation therapy. Subsequent doses were adjusted according to observed toxicity and protocol guidelines. Adverse events were assessed with Common Terminology Criteria for Adverse Events v 3.0. The primary measure of efficacy was tumor response according to Response Evaluation Criteria in Solid Tumors. The study was stratified by prior radiation therapy.ResultsFrom September 2008 to November 2011, 55 patients were enrolled by five Gynecologic Oncology Group member institutions; of those, 54 patients were eligible and assessable. The regimen was well tolerated with 26% receiving more than nine cycles. The most common greater than grade 2 toxicities were neutropenia 35%, leukopenia 28%, and metabolic 28%. The overall response rate was 31% (one complete and 16 partial). The median progression-free survival was 5.7 months, and overall survival was 12.3 months.ConclusionPemetrexed in combination with cisplatin demonstrates activity in the treatment of advanced, persistent, or recurrent carcinoma of the cervix.
| S-EPMC4145184 | biostudies-literature
Project description:Background and objectiveHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, especially in China. According to the 2021 Chinese Society of Clinical Oncology guidelines, sorafenib, lenvatinib, atezolizumab combined with bevacizumab, and sintilimab combined with bevacizumab are recommended as first-line treatment options for advanced HCC. This study provides a cost-effectiveness analysis of these treatments from the patient perspective.MethodsA partitioned survival model was established using the TreeAge 2019 software to evaluate the cost-effectiveness. The model includes three states, namely progression-free survival, progressive disease, and death. Clinical data were derived from three randomized controlled studies involving patients with advanced HCC who received the following treatment: sorafenib and lenvatinib (NCT01761266); atezolizumab in combination with bevacizumab (NCT03434379); and sintilimab in combination with bevacizumab (NCT03794440). Cost and clinical preference data were obtained from the literature and interviews with clinicians.ResultsAll compared with sorafenib therapy, lenvatinib had an incremental cost-effectiveness ratio (ICER) of US$188,625.25 per quality-adjusted life year (QALY) gained; sintilimab plus bevacizumab had an ICER of US$75,150.32 per QALY gained; and atezolizumab plus bevacizumab had an ICER of US$144,513.71 per QALY gained. The probabilistic sensitivity analysis indicated that treatment with sorafenib achieved a 100% probability of cost-effectiveness at a threshold of US$36,600/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the medical insurance reimbursement ratio and drug prices.ConclusionsIn this economic evaluation, therapy with lenvatinib, sintilimab plus bevacizumab, and atezolizumab plus bevacizumab generated incremental QALYs compared with sorafenib; however, these regimens were not cost-effective at a willingness-to-pay threshold of US$36,600 per QALY. Therefore, some patients may achieve preferred economic outcomes from these three therapies by tailoring the regimen based on individual patient factors.
| S-EPMC10064722 | biostudies-literature
Project description:BackgroundSorafenib and transarterial chemoembolization (TACE) might both provide survival benefit for advanced hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. We aimed to estimate the cost-effectiveness of sorafenib and TACE in advanced HCC.MethodsA Markov model was constructed in a hypothetical cohort of patients aged 60 years with advanced HCC and Child-Pugh A/B cirrhosis over a 2-year time frame. Three strategies (full or dose-adjusted sorafenib and TACE) were compared in two cost settings: China and the USA. Transition probabilities, utility and costs were extracted from systematic review of 27 articles. Sensitivity analysis and Monte Carlo analysis were conducted.ResultsFull and dose-adjusted sorafenib respectively produced 0.435 and 0.482 quality-adjusted life years (QALYs) while TACE produced 0.375 QALYs. The incremental cost-effectiveness ratio (ICER) of full-dose sorafenib versus TACE was $101,028.83/QALY in China whereas full-dose sorafenib is a dominant strategy (ICER of -$1,014,507.20/ QALY) compared with TACE in the USA. Compared to full-dose sorafenib, dose-adjusted sorafenib was the dominant strategy with the negative ICERs in both China (-$132,238.94/QALY) and the USA (-$230,058.09/QALY). However, dose-adjusted sorafenib is not available currently, so full-dose sorafenib should be compared with TACE. As the acceptability curves shown, full-dose sorafenib was the optimal strategy at the accepted thresholds of WTP in these two countries. Specifically, full-dose sorafenib was the cost-effective treatment compared with TACE if a WTP was set above $21,670 in the USA, whereas in China, TACE could be more favorable than full-dose sorafenib if a WTP was set below $10,473.ConclusionsDose-adjusted sorafenib may be cost-effective compared to full-dose sorafenib or TACE for advanced HCC patients. However, when confining the comparisons between full-dose sorafenib and TACE, full-dose sorafenib was cost-effective for these patients, under the accepted thresholds of WTP.
| S-EPMC5887167 | biostudies-literature
Project description:Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients.Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6months and objective tumor response.Of 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2cycles of brivanib with 4 (14%) receiving >10cycles (range: 1-20). Seven (25%) patients had PFS >6months (90% CI: 7.3%-33.9%). Two (7%) (90% CI: 1.3%-20.8%) patients had partial tumor response with duration of 8 and 22months and 12 (43%) had stable disease. The median PFS was 3.2months (90% CI: 2.1-4.4). The median overall survival was 7.9months (90% CI: 6.1-11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension.Based on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability.
| S-EPMC5728988 | biostudies-literature
Project description:BACKGROUND: Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC. METHODOLOGY/PRINCIPAL FINDINGS: Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCC patients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1). Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan-Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy.
| S-EPMC3306296 | biostudies-literature
Project description:BackgroundDespite the extensive use of bevacizumab in a range of oncology indications, the US FDA revoked its approval for breast cancers, and multiple negative trials in several solid malignancies have been reported, so the need for predictive biomarkers has increased. The development of predictive biomarkers for anti-angiogenic bevacizumab therapy has long been pursued but without success.IntroductionHeat shock protein (HSP)-27 expression has recently been identified as a predictive biomarker for bevacizumab in treating metastatic melanoma. This study aimed to evaluate the cost effectiveness of HSP27 biomarker testing before administration of bevacizumab.MethodsA partitioned survival analysis model with three mutually exclusive health states (progression-free survival, progressed disease, and death) was developed using a Norwegian health system perspective. The proportion of patients in each state was calculated using the area under the Kaplan-Meier curve for progression-free and overall survival derived from trials of bevacizumab and dacarbazine. Three strategies were compared: (1) test-treat with HSP27 biomarker and bevacizumab, (2) treat-all with dacarbazine without HSP27 testing, (3) treat-all with bevacizumab without HSP27 testing. Quality-adjusted life-years (QALYs) and costs were calculated for each strategy and discounted at 4%. A lifetime horizon was applied. Uncertainty analyses were performed. Expected value of perfect information (EVPI) was estimated to assess the potential value of further research to generate more evidence.ResultsAlthough the test-treat strategy was cost effective compared with treat-all with dacarbazine, it was not cost effective compared with treat-all with bevacizumab without HSP27 testing. However, EVPI results showed very minimal or no value in conducting further research efforts to reduce uncertainties around current information.ConclusionThe results of this study suggested that testing for HSP27 expression before administering bevacizumab is not cost effective compared with treat-all with bevacizumab without testing. It indicates that HSP27 expression is not cost effective as a potential predictive biomarker for bevacizumab. This may not necessarily mean that HSP27 is a bad biomarker for bevacizumab, but it may mean that bevacizumab is much better than dacarbazine regardless of HSP27 expression, so patient stratification according to HSP27 status is meaningless. Or, indeed, it may imply that HSP27 is not sufficiently good at identifying the right patients for bevacizumab.
| S-EPMC7426343 | biostudies-literature
Project description:The effective exploitation of the intriguing theranostic features of noble metal nanoparticles for therapeutic applications is far from being a routine practice due to the persistence issue. In this regard, passion fruit-like nano-architectures (NAs), biodegradable and excretable all-in-one, nature-inspired platforms which jointly combine these characteristics with the appealing optical behaviors of noble metal nanoparticles, can offer a new alternative for theranostic applications. Besides the need for efficacious and innovative systems, the reliable and cost-effective production of nanomaterials is a pivotal subject for their translation to the clinical setting. Here, we demonstrate the production of a new cheaper class of degradable, ultrasmall-in-nano-architectures (dragon fruit NAs, dNAs) using polyethyleneimine (PEI) as a cationic polymer without affecting either their compositions or their physiological behaviors, compared to the previous NAs. In particular, the standardized protocol characterized in this work ensures the preparation of high gold-loading capacity nanoparticles, a peculiar characteristic that, synergically with the interesting properties of PEI, may unlock new possible applications previously precluded to the first version of NAs while reducing the hand-made production cost by three orders of magnitude.
| S-EPMC7466706 | biostudies-literature
Project description:BACKGROUND:We sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene-specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA). METHODS:The tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene-specific alteration frequencies were compared (Chi-Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform. RESULTS:Persistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53. CONCLUSIONS:Our results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.
| S-EPMC6431792 | biostudies-literature
Project description:We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix.Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m(2) day 1, topotecan 0.75 mg/m(2) days 1, 2 and 3 and bevacizumab 15 mg/kgday 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy.Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities.The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity.
| S-EPMC3870479 | biostudies-literature