Health Technology Assessment

Bevacizumab in combination with a taxane for the first-line treatment of HER2-negative metastatic breast cancer

  • Type:
    Extended Research Article
  • Authors:
    M Rodgers,
    M Soares,
    D Epstein,
    H Yang,
    D Fox,
    A Eastwood
    Detailed Author information

    M Rodgers1,*, M Soares2, D Epstein2, H Yang1, D Fox1, A Eastwood1

    • 1 Centre for Reviews and Dissemination, University of York, York, UK
    • 2 Centre for Health Economics, University of York, York, UK
  • Funding:
    Health Technology Assessment programme
  • Journal:
    Health Technology Assessment
  • Issue:
    Volume: 15, Issue: Suppl 1 Article 1
  • Published:
  • Citation:
    Rodgers M, Soares M, Epstein D, Yang H, Fox D, Eastwood A. Bevacizumab in combination with a taxane for the first-line treatment of HER2-negative metastatic breast cancer. Health Technol Assess 2011;15(Suppl 1 Article 1). https://doi.org/10.3310/hta15Suppl1-01
  • DOI:
    https://doi.org/10.3310/hta15Suppl1-01
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The research reported in this article of the journal supplement was commissioned and funded by the HTA programme on behalf of NICE as project number 09/25/01. The assessment report began editorial review in July 2010 and was accepted for publication in July 2010. See the HTA programme website for further project information (www.hta.ac.uk). This summary of the ERG report was compiled after the Appraisal Committee’s review. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.

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© Queen’s Printer and Controller of HMSO 2011. This work was produced under the terms of a commissioning contract issued by the Secretary of State for Health. This journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (http://www.publicationethics.org/). This journal may be freely reproduced for the purposes of private research and study and may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NETSCC, Health Technology Assessment, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

2011 Queen’s Printer and Controller of HMSO

This paper presents a summary of the evidence review group (ERG) report into the use of bevacizumab (Avastin®, Roche) in combination with a taxane for the treatment of untreated metastatic breast cancer (mBC). The main clinical effectiveness data were derived from a single, open-label randomised controlled trial (RCT) (E2100) that evaluated the addition of bevacizumab to weekly (q.w.) paclitaxel in patients with human epidermal growth factor receptor 2-negative mBC who had not previously received chemotherapy for advanced disease. This trial reported statistically significant increases in median progression-free survival (PFS) for the addition of bevacizumab (5.8–11.3 months). Median overall survival was not significantly different between the two groups; whether this is a true null finding or due to crossover between treatment arms cannot be established, as relevant data were not collected. The manufacturer reported that the addition of bevacizumab to paclitaxel q.w. therapy was associated with a significant improvement in quality of life, as measured by FACT-B (functional assessment of cancer therapy for breast cancer) scores. However, the ERG noted that these results were based on extreme imputed values, the removal of which led to non-significant differences in quality of life. The manufacturer conducted an indirect comparison. However, owing to methodological limitations and concerns about the validity and exchangeability of the included trials, the ERG did not consider the findings to be reliable. One additional relevant RCT [AVADO (Avastin and Docetaxel); BO17708] evaluating the addition of bevacizumab to docetaxel was excluded from the manufacturer’s submission. This was summarised by the ERG. In terms of response rate and PFS, AVADO reported a markedly smaller benefit of adding bevacizumab to docetaxel than that reported for adding bevacizumab to q.w. paclitaxel in E2100. AVADO also reported no statistically significant effect of combination therapy versus docetaxel in terms of overall survival. The manufacturer developed a de novo economic model that considered patients with the same baseline characteristics as women in the E2100 trial. The model assessed BEV + PAC – bevacizumab 10 mg/kg every 2 weeks in combination with paclitaxel 90 mg/m2 weekly for 3 weeks followed by 1 week of rest; PAC q.w. – paclitaxel (monotherapy) 90 mg/m2 weekly for 3 weeks followed by 1 week of rest; DOC – docetaxel (monotherapy) 75 mg/m2 on day 1 every 21 days (considered current UK NHS clinical practice in the submission); and GEM + PAC – gemcitabine 1250 mg/m2 on days 1 and 8 plus paclitaxel 175 mg/m2 on day 1 every 21 days. Pairwise comparisons were made between BEV + PAC and PAC (using the E2100 trial), BEV + PAC and DOC, and BEV + PAC and GEM + PAC. Based on NHS list prices, the manufacturer’s model estimated incremental cost-effectiveness ratios (ICERs) for BEV + PAC of £117,803, £115,059 and £105,777 per QALY gained, relative to PAC, DOC and GEM + PAC regimens, respectively. If the NHS Purchasing and Supply Agency prices for PAC with a 10-g cap on the cost per patient of BEV were used instead, the ICERs for BEV + PAC were estimated at £77,314, £57,753 and £60,101 per QALY, respectively. The submission suggested that the regimen of BEV + DOC is not cost-effective because it is considered less effective and more costly than BEV + PAC. Analysis by the ERG suggested that alternative assumptions can increase the ICERs further and, based on current prices, no plausible changes to the model assumptions will bring the ICERs for BEV + PAC lower.

Introduction

The National Institute for Health and Clinical Excellence (NICE) is an independent organisation within the NHS which is responsible for providing national guidance on the treatment and care of people using the NHS in England and Wales. One of the responsibilities of NICE is to provide guidance to the NHS on the use of selected new and established health technologies, based on an appraisal of those technologies.

NICE’s single technology appraisal (STA) process is specifically designed for the appraisal of a single product, device or other technology, with a single indication, where most of the relevant evidence lies with one manufacturer or sponsor (in this instance, Roche). Typically, it is used for new pharmaceutical products that are close to launch. The principal evidence for an STA is derived from a submission by the manufacturer/sponsor of the technology. In addition, a report reviewing the evidence submission is submitted by the evidence review group (ERG), an external organisation independent of the Institute. This paper presents a summary of the ERG report for the STA entitled Bevacizumab in combination with a taxane for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.

Description of the underlying health problem

Breast cancer is the most common cancer in the UK, with almost 45,700 women diagnosed with the disease in 2007. 1 The incidence rates of female breast cancer in the UK have increased by 5% in the last 10 years,1 and around 260 men are also diagnosed each year. 2,3 In 2008, there were 12,116 deaths from breast cancer in the UK; 12,047 (99%) of these were women and 69 (1%) were men. 4 It is estimated that 16–20% of women diagnosed with breast cancer have advanced disease with metastases, and around 50% of those diagnosed with early (or localised) breast cancer will eventually develop metastatic cancer. 5

Current UK treatment depends on patients’ previous therapy, human epidermal growth factor receptor 2 (HER2) status and oestrogen receptor status. First-line therapy for metastatic breast cancer (mBC) is usually an anthracycline-based regimen; when an anthracycline is not considered appropriate, NICE clinical guideline 81 recommends docetaxel monotherapy as the first-line therapy. 6 Vinorelbine or capecitabine monotherapy is recommended for subsequent treatment. 6

Scope of the evidence review group report

The decision problem specified by NICE was the use of bevacizumab (Avastin®, Roche), in combination with a taxane, for the treatment of untreated metastatic HER2-negative breast cancer in patients for whom anthracyclines are not appropriate. Bevacizumab is licensed for the first-line treatment of HER2-negative mBC. The decision problem specified that bevacizumab in combination with paclitaxel should be compared with bevacizumab in combination with docetaxel; other comparators specified were docetaxel monotherapy, paclitaxel monotherapy and paclitaxel in combination with gemcitabine.

The outcome measures considered were overall survival (OS), progression-free survival (PFS), response rates, adverse events, health-related quality of life and incremental cost per quality-adjusted life-year (QALY) gained.

Methods

The ERG report comprised a critical review of the evidence for the clinical effectiveness and cost-effectiveness of the technology based upon the manufacturer’s submission (MS) to NICE as part of the STA process.

The ERG appraised the literature searches and carried out a search for ongoing trials. The systematic review methodology was appraised and, owing to the limited quality assessment of included trials in the MS, the ERG performed additional quality assessment. The manufacturer’s economic evaluation was appraised using a validated checklist7 and a descriptive critical review, and the decision model was validated by running the model and conducting sensitivity analyses. The ERG also constructed a de novo decision model in excel (Microsoft Corporation, Redwood, WA, USA) to explore sensitivity analyses and scenarios that were not fully addressed by the manufacturer’s model.

Results

Summary of submitted clinical evidence

The clinical effectiveness data were primarily derived from a single, open-label randomised controlled trial (RCT) (E21008–16) that evaluated the addition of bevacizumab to weekly (q.w.) paclitaxel in patients with HER2-negative mBC who had not previously received chemotherapy for advanced disease. The trial reported statistically significant increases in median PFS from 5.8 to 11.3 months [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.44 to 0.67] for bevacizumab plus paclitaxel versus paclitaxel alone (Table 1). Median OS was not significantly different between the two groups (26.5 vs 24.8 months; HR 0.87, 95% CI 0.72 to 1.05). A post hoc analysis indicated that OS at 1 year was significantly higher with paclitaxel plus bevacizumab than with paclitaxel alone (81.4% vs 74.0%, p = 0.017). The addition of bevacizumab to paclitaxel therapy was associated with a significant improvement in quality of life as measured by the FACT-B (functional assessment of cancer therapy for breast cancer) trial outcome index (TOI-B) score at week 33 (p = 0.0042) and by the FACT-B total score (TOT-B) at week 17 (p = 0.0475) and week 33 (p = 0.0046) compared with paclitaxel alone.

E21008–16 AVADO17–26
Participants HER2-negative mBC not previously treated with chemotherapy (n = 722) HER2-negative previously untreated locally recurrent or mBC (n = 736)
Intervention Bevacizumab 10 mg/kg + paclitaxel 90 mg/m2, q.w.

Bevacizumab 7.5 mg/kg + docetaxel 100 mg/m2, q3w

Bevacizumab 15 mg/kg + docetaxel 100 mg/m2, q3w
Comparator Paclitaxel 90 mg/m2, q.w. Placebo + docetaxel: docetaxel 100 mg/m2, q3w
Length of follow-up for the analysis Patients were enrolled between December 2001 and May 2004 Patients were enrolled between March 2006 and April 2007

PFS and objective response

Data collected prior to 9 February 2005

PFS

Primary analysis: median follow-up 10.2 months

Updated analysis: conducted at time of final OS analysis (additional 18 months of follow-up)

OS

Data collected prior to 21 October 2006

OS

Median follow-up 25 months
Paclitaxel (n = 354) Bevacizumab + paclitaxel (n = 368) Docetaxel + placebo (n = 241) Bevacizumab 7.5 mg/kg + docetaxel (n = 248) Bevacizumab 15 mg/kg + docetaxel (n = 247)
Median PFS (months) 5.8 11.3 8.0 8.7 8.8
8.2a 9.0a 10.1a
PFS: HR (95% CI) – 0.48 (0.39 to 0.61) – 0.79 (0.63 to 0.98) 0.72 (0.57 to 0.90)
–a 0.86 (0.72 to 1.04)a 0.77 (0.64 to 0.93)a
Response rate (%) 22.2 49.8 44.4 55.2 63.1
46.4a 55.2a 64.1a
OS: HR (95% CI) – 0.87 (0.72 to 1.05) – 1.05 (0.81 to 1.36) 1.03 (0.79 to 1.33)

AVADO, Avastin and Docetaxel (BO17708); CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; mBC, metastatic breast cancer; OS, overall survival; PFS, progression-free survival; q.w., weekly; q3w, 3-weekly.

Updated analysis applies for the AVADO trial only.

The manufacturer conducted an indirect comparison based on the method described by Bucher et al. 27 This reported that bevacizumab plus q.w. paclitaxel was associated with a significant improvement in PFS when compared with 3-weekly (q3w) docetaxel (HR 0.56, 95% CI 0.39 to 0.78) and with gemcitabine plus q3w paclitaxel (HR 0.46, 95% CI 0.34 to 0.64). No significant difference was found for PFS between q.w. paclitaxel and q3w docetaxel (HR 1.15, 95% CI 0.89 to 1.48) or between q.w. paclitaxel and gemcitabine plus q3w paclitaxel (HR 0.96, 95% CI 0.76 to 1.21).

On the basis of the E2100 study and a large uncontrolled study [ATHENA (Avastin Therapy for Advanced Breast Cancer); MO19391],28–34 the manufacturer concluded that bevacizumab is not associated with the commonly recognised side effects of cytotoxic anticancer therapies and that the most common adverse events associated with bevacizumab therapy are hypertension and proteinuria.

Summary of submitted cost-effectiveness evidence

The submission identified six cost-effectiveness analyses but stated that they were not relevant as they were all conducted outside the UK. The manufacturer, therefore, justified the development of a de novo economic model that considered patients with the same baseline characteristics as seen in women in the E2100 trial. 8–16 The model assessed:

  • BEV + PAC bevacizumab 10 mg/kg (every 2 weeks) in combination with paclitaxel 90 mg/m2 (weekly for 3 weeks followed by 1 week of rest)

  • PAC q.w. paclitaxel (monotherapy) 90 mg/m2 weekly for 3 weeks followed by 1 week of rest

  • DOC docetaxel (monotherapy) 75 mg/m2 on day 1 every 21 days (considered current UK NHS clinical practice in the submission)

  • GEM + PAC gemcitabine 1250 mg/m2 on days 1 and 8 plus paclitaxel 175 mg/m2 on day 1 every 21 days.

Pairwise comparisons were made between BEV + PAC and PAC (using the E2100 trial8–16), BEV + PAC and DOC, and BEV + PAC and GEM + PAC.

The model was a Markov model with three states (progression free, progressed and dead) and used a 10-year time horizon. Parametric survival functions were used to model the rate of metastatic disease progression based on data from the E2100 trial. 8–16 Based on the results of the indirect comparison of treatment effects, it was assumed that the rate of disease progression was the same after PAC q.w. as after DOC and after GEM + PAC. It was assumed that the hazard of death after progression was constant over time and the same across all treatments, meaning that any difference in PFS between treatments is mirrored in terms of OS. The costs and disutility associated with treatment-related adverse events were included, based on the incidence of events in the E2100 trial. 8–16 Utility estimates were derived from a non-systematic literature review of studies of patients with breast cancer. A number of cost categories were considered: drug acquisition, drug administration, duration of treatment, supportive care, adverse event and end of life. Two alternative base-case analyses were presented for the acquisition costs of the drugs: product list prices (British National Formulary35) and PASA (Purchasing and Supply Agency, NHS) prices for paclitaxel along with a capping scheme for the cost to the NHS of bevacizumab.

Based on NHS list prices, the manufacturer’s model estimated incremental cost-effectiveness ratios (ICERs) for BEV + PAC of £117,803, £115,059 and £105,777 per QALY gained, relative to PAC, DOC and GEM + PAC regimens, respectively. If PASA prices for PAC with a 10-g cap on the cost per patient of BEV are used instead, the ICERs for BEV + PAC are estimated at £77,314, £57,753 and £60,101 per QALY, respectively. The manufacturer stated that the regimen of BEV + DOC would not be cost-effective compared with BEV + PAC because it is considered less effective and more costly than BEV + PAC, but did not conduct an economic evaluation to compare these regimens. Table 2 shows the results of the manufacturer’s model for BEV + PAC versus PAC q.w.

Scenario Analyst Intervention and comparator Source of cost data Source of effectiveness data Incremental cost (£) Incremental QALY ICER (£)
1 MS BEV + PAC vs PAC q.w. List prices E2100 PFS 30,469 0.259 117,803
2 MS BEV + PAC vs PAC q.w. PASA prices with cap on BEV E2100 PFS 19,997 0.259 77,314
3 ERG BEV + PAC vs PAC q.w. PASA prices and no cap E2100 PFS 28,573 0.259 110,475
4 ERG BEV + DOC vs DOC q3w List prices AVADO PFS 34,712 0.136 254,530
5 ERG BEV + PAC vs PAC q.w. List prices E2100 OS 29,675 0.114 259,267

AVADO, Avastin and Docetaxel (BO17708); BEV, bevacizumab; DOC, docetaxel; ERG, evidence review group analysis; ICER, incremental cost-effectiveness ratio; MS, manufacturer’s submission; OS, overall survival – QALYs based on extrapolation from estimates of OS; PAC, paclitaxel; PASA, NHS Purchasing and Supply Agency (including discounts); PFS, progression-free survival – QALYs based on extrapolation from estimates of PFS; QALY, quality-adjusted life-year; q.w., weekly; q3w, 3-weekly.

Commentary on the robustness of submitted evidence

Strengths

The manufacturer’s systematic review of the literature used appropriate search methods. The E21008–16 RCT was conducted in a relevant population and steps were taken to mitigate against methodological limitations (e.g. intention-to-treat analyses of independently reviewed outcomes were undertaken). The safety evaluation included the most comprehensive and robust study available to assess this outcome.

The MS largely conforms to the NICE reference case for cost-effectiveness analysis and was reasonably clearly presented.

Weaknesses

The manufacturer’s search identified a second RCT (the AVADO trial17–26) that evaluates the addition of bevacizumab to q3w docetaxel. The manufacturer excluded this trial because they considered the docetaxel dose unrepresentative of UK clinical practice, but this conflicted with clinical advice given to the ERG.

The manufacturer identified an existing economic evaluation but stated that as it was populated with Swiss unit costs the results were not relevant to the NHS. 36 However, the effectiveness estimate used in this study was based on PFS and OS in the E2100 trial8–16 and therefore has some relevance to this appraisal. This analysis found that the ICER for BEV + PAC versus PAC q.w. was €189,000 per QALY.

Limitations in the collection and analysis of data in E21008–16 affect the reliability of the trial’s findings. Data were not collected on the treatment regimens received by patients after disease progression; therefore, the influence of postprogression treatment on OS in this trial is unknown. Also, the significant improvements in quality of life reported in E21008–16 were based on analyses using extreme imputed data for missing values; without these imputed data, differences between groups are statistically insignificant. These data were not further used in the cost-effectiveness model.

The ERG identified several methodological limitations relating to the indirect comparison. One inclusion criterion (< 60% of patients receiving second-line chemotherapy for mBC) may have been formulated to allow the inclusion of a specific trial. The AVADO trial17–26 was excluded from the indirect comparison on the basis of docetaxel dose, but another trial that used the same dose was included. 37 One included trial38 had compromised internal validity owing to an imbalance in the proportion of patients receiving second-line treatment between the q.w. (16%) and q3w (41%) paclitaxel arms. There was also a lack of similarity in terms of the proportion of patients receiving second-line treatment between included trials (e.g. 55% in Jones et al. ,37 0% in E21008–16 and Albain et al. 39), highlighting the issue of exchangeability between treatment effects and different patient samples. Given these methodological limitations identified, the ERG did not consider the findings of the indirect comparison to be reliable.

The manufacturer’s cost-effectiveness model did not consider all relevant comparators. Specifically, bevacizumab in combination with either docetaxel or q3w paclitaxel were not formally considered despite the latter being used in clinical practice in the UK. The manufacturer assumed that the rate of death after progression is constant over time and the same for all initial treatments, with the implication that differences in mean PFS between treatments are maintained in the mean OS estimates. However, the E2100 RCT did not find any statistically significant differences in OS, despite finding a statistically significant difference in PFS. The manufacturer stated that this might be because patients received different treatments after progression in each arm, including bevacizumab after failure of paclitaxel monotherapy. However, this may be a strong assumption and alternative model structures were not considered by the manufacturer. The manufacturer’s model predicted a greater difference in OS for BEV + PAC versus PAC than in the result of the E2100 trial. 8–16

The base-case model assumed that the regimens PAC, DOC and GEM + PAC are equally effective; no alternative scenarios were presented.

Despite the use of a disease-specific health-related quality of life instrument in the E2100 trial8–16 (the FACT-B), no mapping algorithm was used to link this to a preference-based (utility) instrument, such as the European Quality of Life-5 Dimensions (EQ-5D). Instead, external utility estimates were used based on a literature search, which was not systematic. No attempt was made to collate or synthesise the alternative estimates, and the selection of utilities for the model appeared arbitrary.

In an alternative base case, the analysis assumed that the cost of bevacizumab would be capped at 10 g per patient. The ERG understands that the price cap assumed for bevacizumab has not been agreed with the Department of Health and should not, therefore, have been assumed in the model. The patent for docetaxel expired in November 2010, but the manufacturer did not explore the implications of a likely reduction in its acquisition cost. The analysis also ignored the possibility of dose reductions. The extent to which dose reductions occur may differ between alternative treatments, and the ERG expects this to affect the results. The manufacturer undertook no subgroup analysis. The model results were presented as a series of pairwise ICERs comparing BEV + PAC individually with the alternative regimens. This is inappropriate and a full incremental analysis should have been undertaken.

Areas of uncertainty

Efficacy outcomes for bevacizumab plus q.w. paclitaxel versus q.w. paclitaxel alone were based on an interim analysis of the E2100 trial. 8–16 PFS and response data were collected up to February 2005 and OS data were collected up to October 2006. Analysis of more complete follow-up data would be valuable, although the manufacturer stated that no such analyses are available.

The reason for the lack of OS benefit for combination therapy observed in the E2100 trial8–16 cannot be established, as data on postprogression treatment were not collected.

Methodological limitations in the indirect comparison mean that the relative efficacy of bevacizumab plus q.w. paclitaxel versus comparators other than paclitaxel alone, outlined in the decision model, remains highly uncertain.

The methodological weaknesses in the model described above give rise to a number of uncertainties; the ERG undertook a series of analyses to explore their implications.

The use of the PASA discount (without the cap on the costs of BEV) made little difference to the incremental costs of BEV + PAC versus PAC, compared with using NHS list prices (see Table 2).

The ERG evaluated BEV+DOC versus DOC alone based on the results of the AVADO RCT. 17–26 This found that the ICER was more than £250,000 per QALY (see Table 2).

The ERG constructed an alternative model that was calibrated to the E21008–16 results for OS. The ICER of BEV + PAC versus PAC q.w. was > £250,000 per QALY in the revised model (see Table 2). This result should be considered a ‘worst-case’ scenario regarding the cost-effectiveness of BEV + PAC versus PAC q.w. because it is assumed that there is no difference in OS. The manufacturer’s model might be considered a ‘best-case’ scenario as it assumes that the difference in PFS from the E2100 trial would be fully reflected in an equivalent difference in OS in clinical practice.

Conclusions

Despite some methodological limitations, the E2100 trial8–16 provides direct evidence to suggest that the addition of bevacizumab to q.w. paclitaxel increases PFS and objective response in the first-line treatment of mBC. This trial fails to show a significant benefit in terms of OS. The ERG noted that the manufacturer inappropriately excluded the large relevant AVADO trial in which the docetaxel dosing regime was generally reflective of UK current practice. The ERG extracted the limited available published data from this trial,17–26 which reported a markedly smaller benefit in terms of PFS and response rate of adding bevacizumab to docetaxel than was reported for adding bevacizumab to q.w. paclitaxel in E21008–16 (see Table 1). The AVADO trial also reported a non-significant benefit in combination therapy versus docetaxel monotherapy in terms of OS. 17–26

Given the considerable limitations in the evidence selected and methods used for the indirect comparison, the manufacturer’s reporting of a statistically significant benefit of bevacizumab plus q.w. paclitaxel over the currently recommended first-line treatment of docetaxel monotherapy cannot be considered reliable.

The cost-effectiveness analysis presented by the manufacturer included judgements and assumptions that are subject to uncertainty. The manufacturer’s most optimistic analyses suggested an ICER for BEV + PAC versus PAC q.w. of £77,000 per QALY gained using PASA prices for PAC and a 10-g cap on BEV, and £118,000 using NHS list prices. Further analysis by the ERG suggested that more pessimistic assumptions about the relative impact of bevacizumab on OS can increase the ICERs yet further, and, based on current prices, no plausible changes to the model assumptions will bring the ICER for BEV + PAC versus PAC q.w. within the threshold currently considered cost-effective by NICE.

Summary of NICE guidance issued as a result of the STA

The guidance document issued by NICE in February 2011 states that bevacizumab in combination with a taxane is not recommended for first-line treatment of metastatic breast cancer. Following consultation on the appraisal consultation document, the manufacturer provided additional subgroup data; the ERG provided commentary and validity checks on the additional evidence submitted by the manufacturer, as requested by NICE.

During the course of this appraisal, the European Medicines Agency (EMA) conducted a review of the use of bevacizumab in combination with taxanes for the tretment of mBC. Following that review, the EMA’s Committee for Medicinal Products for Human Use recommended that bevacizumab, when used to treat mBC, should be used only in combination with the taxane, paclitaxel.

Acknowledgements

The ERG would like to thank Professor Galina Velikova (Professor of Psychosocial and Medical Oncology, St James’s Institute of Oncology, Leeds) for providing clinical advice and commenting on drafts of the report, as well as Steve Palmer [Senior Research Fellow, Centre for Health Economics (CHE)] and Mark Sculpher (Professor of Health Economics, CHE) for their advice and comments on this report.

Disclaimers

The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health.

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