Decisions on Further Research for Predictive Biomarkers of High-Dose Alkylating Chemotherapy in Triple-Negative Breast Cancer: A Value of Information Analysis.

OBJECTIVES: To inform decisions about the design and priority of further studies of emerging predictive biomarkers of high-dose alkylating chemotherapy (HDAC) in triple-negative breast cancer (TNBC) using value-of-information analysis. METHODS: A state transition model compared treating women with TNBC with current clinical practice and four biomarker strategies to personalize HDAC: 1) BRCA1-like profile by array comparative genomic hybridization (aCGH) testing; 2) BRCA1-like profile by multiplex ligation-dependent probe amplification (MLPA) testing; 3) strategy 1 followed by X-inactive specific transcript gene (XIST) and tumor suppressor p53 binding protein (53BP1) testing; and 4) strategy 2 followed by XIST and 53BP1 testing, from a Dutch societal perspective and a 20-year time horizon. Input data came from literature and expert opinions. We assessed the expected value of partial perfect information, the expected value of sample information, and the expected net benefit of sampling for potential ancillary studies of an ongoing randomized controlled trial (RCT; NCT01057069). RESULTS: The expected value of partial perfect information indicated that further research should be prioritized to the parameter group including "biomarkers' prevalence, positive predictive value (PPV), and treatment response rates (TRRs) in biomarker-negative patients and patients with TNBC" (€639 million), followed by utilities (€48 million), costs (€40 million), and transition probabilities (TPs) (€30 million). By setting up four ancillary studies to the ongoing RCT, data on 1) TP and MLPA prevalence, PPV, and TRR; 2) aCGH and aCGH/MLPA plus XIST and 53BP1 prevalence, PPV, and TRR; 3) utilities; and 4) costs could be simultaneously collected (optimal size = 3000). CONCLUSIONS: Further research on predictive biomarkers for HDAC should focus on gathering data on TPs, prevalence, PPV, TRRs, utilities, and costs from the four ancillary studies to the ongoing RCT.

The clinical effectiveness and cost-effectiveness of bortezomib and thalidomide in combination regimens with an alkylating agent and a corticosteroid for the first-line treatment of multiple myeloma: a systematic review and economic evaluation.

BACKGROUND: Multiple myeloma (MM) is the second most common haematological cancer in the UK. MM is not curable but can be treated with a combination of supportive measures and chemotherapy that aim to extend the duration and quality of survival. The majority of patients are not able to withstand intensive treatment, such as high-dose chemotherapy with autologous stem cell transplantation (SCT), and so they are offered single-agent or combination chemotherapy. Combination therapies typically include chemotherapy with an alkylating agent and a corticosteroid. More recently, combination therapies have incorporated drugs such as thalidomide (Thalidomide Celgene®, Celgene) and bortezomib (Velcade®, Janssen-Cilag). OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of bortezomib or thalidomide in combination chemotherapy regimens with an alkylating agent and a corticosteroid for the first-line treatment of MM. DATA SOURCES: Electronic bibliographic databases, including MEDLINE, EMBASE and The Cochrane Library, were searched from 1999 to 2009 for English-language articles. Bibliographies of articles, grey literature sources and manufacturers' submissions were also searched. Experts in the field were asked to identify additional published and unpublished references. REVIEW METHODS: Titles and abstracts were screened for eligibility by two reviewers independently. The inclusion criteria specified in the protocol were applied to the full text of retrieved papers by one reviewer and checked independently by a second reviewer. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Differences in opinion were resolved through discussion at each stage. A cost-utility decision-analytic model was used to compare the cost-effectiveness estimates of bortezomib in combination with melphalan and prednisolone/prednisone (VMP), thalidomide in combination with cyclophosphamide and attenuated dexamethasone (CTDa), and thalidomide in combination with melphalan and prednisolone/prednisone (MPT) versus melphalan and prednisolone/prednisone (MP). RESULTS: A total of 1436 records were screened and 40 references were retrieved for the systematic review of clinical effectiveness. Five randomised controlled trials (RCTs) met the inclusion criteria for the review: one RCT evaluated VMP, three evaluated MPT and one evaluated CTDa. The comparator in all of the included trials was MP. The review found that VMP and MPT can both be considered more clinically effective than MP for the first-line treatment of MM in people for whom high-dose therapy and SCT would not be appropriate. CTDa was more effective than MP in terms of complete response but data on survival outcomes did not meet the inclusion criteria. Cost-effectiveness analysis indicated that MPT has a greater probability of being cost-effective than either VMP or CTDa. LIMITATIONS: For most RCTs, details needed to judge study quality were incompletely reported. All studies stated that the analyses followed intention-to-treat principles but none adequately reported data censoring. Only one RCT contributed data on VMP and the published peer-reviewed follow-up data were immature. For MPT, overall survival data from two trials were eligible for inclusion but the doses of thalidomide differed between the trials and the treatment period was not reflective of current UK practice so the generalisability of the findings was uncertain. Two RCTs had a maintenance phase with thalidomide that did not meet the inclusion criteria so some of these results were not eligible for the review. Limited evidence on health-related quality of life (HRQoL) was provided by the single trial of VMP versus MP. CONCLUSIONS: Service provision is unlikely to change greatly. As uncertainties remain, further research is needed regarding the use of bortezomib- and thalidomide-containing combination regimens. Head-to-head trials of bortezomib- and thalidomide-containing combination regimes are required, including assessments of patient HRQoL in response to treatment. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

[A comparative study of thio-tepa and mitomycin C in the treatment of pterygium. Preliminary results]. / Etude comparative du Thio-tepa et de la Mitomycine C dans le traitement du ptérygion. Résultats préliminaires.

AIMS: To compare the efficacy of Thio-tepa and Mitomycine C to obviate recurrence; to compare cost-efficacy ratios; to evaluate their facility of use and their complications. METHODS: In a prospective blinded study, 36 patients undergoing surgery for 46 primary and recurrent pterygium were assigned randomly to three groups: group 1 received 0.02 mg/ml of Mitomycine C three times daily for 5 days; group 2 received Thio-tepa four times daily for 6 weeks, group 3 served as a control receiving distilled water three times daily for five days. RESULTS: Recurrence rates were 38%, in group 1; 28% in group 2; 82% in group 3 respectively. Follow-up ranged from 15 to 44 weeks (mean 27.93 +/- 8.9 weeks). Mean delay recurrence time was 6.3 weeks. Topical Mitomycin caused: iritis, conjunctival irritation, excessive lacrymation, photophobia, ocular pain; Thio-tepa caused: photophobia, foreign body sensation, headache. CONCLUSIONS: Mitomycine C appears to be an effective and safe adjunctive treatment for this cost-efficacy and this facility of use comparison.