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

Abstract 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.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title health technology assessment (winchester, england)
Publication Year Start




PMID- 21609648
OWN - NLM
STAT- MEDLINE
DCOM- 20120705
LR  - 20161125
IS  - 2046-4924 (Electronic)
IS  - 1366-5278 (Linking)
VI  - 15 Suppl 1
DP  - 2011 May
TI  - Bevacizumab in combination with a taxane for the first-line treatment of
      HER2-negative metastatic breast cancer.
PG  - 1-12
LID - 10.3310/hta15suppl1/01 [doi]
AB  - This paper presents a summary of the evidence review group (ERG) report into the 
      use of bevacizumab (Avastin(R), 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 pound 117,803, pound 115,059 and pound 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 pound 77,314, pound 
      57,753 and pound 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.
FAU - Rodgers, M
AU  - Rodgers M
AD  - Centre for Reviews and Dissemination, University of York, York, UK.
      [email protected]
FAU - Soares, M
AU  - Soares M
FAU - Epstein, D
AU  - Epstein D
FAU - Yang, H
AU  - Yang H
FAU - Fox, D
AU  - Fox D
FAU - Eastwood, A
AU  - Eastwood A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Health Technol Assess
JT  - Health technology assessment (Winchester, England)
JID - 9706284
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Bridged-Ring Compounds)
RN  - 0 (Taxoids)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 15H5577CQD (docetaxel)
RN  - 1605-68-1 (taxane)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - B76N6SBZ8R (gemcitabine)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Angiogenesis Inhibitors/administration & dosage/economics/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/economics/*therapeutic 
      use
MH  - Antineoplastic Agents/administration & dosage/economics/*therapeutic use
MH  - Bevacizumab
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Bridged-Ring Compounds/administration & dosage/economics/*therapeutic use
MH  - Deoxycytidine/analogs & derivatives/therapeutic use
MH  - Disease-Free Survival
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Neoplasm Metastasis
MH  - Paclitaxel/therapeutic use
MH  - Quality-Adjusted Life Years
MH  - Randomized Controlled Trials as Topic
MH  - Receptor, ErbB-2
MH  - Taxoids/administration & dosage/economics/*therapeutic use
EDAT- 2012/04/11 06:00
MHDA- 2012/07/06 06:00
CRDT- 2011/05/26 06:00
PHST- 2011/05/26 06:00 [entrez]
PHST- 2012/04/11 06:00 [pubmed]
PHST- 2012/07/06 06:00 [medline]
AID - 10.3310/hta15suppl1/01 [doi]
PST - ppublish
SO  - Health Technol Assess. 2011 May;15 Suppl 1:1-12. doi: 10.3310/hta15suppl1/01.