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| Journal of the New Zealand Medical Association,
07-July-2006, Vol 119 No 1237
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Breast Cancer Advocacy Coalition responds to the
‘Herceptin or deception’ article
I write on behalf of the Breast Cancer Advocacy Coalition1
to express our disappointment at the publication of Martin Rosevear’s
piece on trastuzumab (Herceptin®) in the 2 June 2006 issue of the
New Zealand Medical Journal.2
The analysis presented does little to help inform the
debate. It does not accurately portray the latest or the most relevant clinical
trial evidence for trastuzumab in early breast cancer. The analysis presented
also takes an extremely superficial view of the economic outcomes associated
with use of trastuzumab in early breast cancer. It further confuses the reader
by presenting clinical outcomes and using assumptions derived from trastuzumab
use in metastatic disease.
In marked contrast to this is the exhaustive process of
evaluating clinical effectiveness and cost-effectiveness of trastuzumab in early
breast cancer recently undertaken in the United Kingdom by the National
Institute of Clinical Excellence (NICE).3 One input to the NICE appraisal was a
review by authors from the School of Health and Related Research at the
University of Sheffield (ScHARR).4 They concluded that trastuzumab in early
breast cancer resulted in a statistically significant relative reduction in the
hazard of all-cause mortality from 24% (HR 0.76, 95%CI 0.47 to 1.23, absolute
risk reduction 0.5%) at a median follow-up of 1-year to 33% (HR 0.67, 95%CI 0.48
to 0.93, absolute risk reduction 1.8%) at median follow-up of 2 years.
The conclusion was that all studies at whatever schedule or
length of follow-up showed a statistically significant relative difference (of
about 50% in every case) in the hazard of recurrence or death from any cause
(disease-free survival), favouring trastuzumab. These early results are
considered unprecedented in the breast cancer field.
The cost-effectiveness analysis undertaken in the United
Kingdom included not only the cost of trastuzumab (to which Rosevear’s
analysis appears to have been limited) but also included other relevant health
sector costs such as drug administration, laboratory costs, cardiovascular
monitoring, ambulatory care, disease recurrence and adverse effects. The NICE
analysis used a model that incorporated quality of life
and survival based on the HERA trial
(upon which the provisional MEDSAFE approval in New Zealand is primarily based)
with rather conservative assumptions. This analysis resulted in an incremental
quality-adjusted life-year (QALY) gain of 2.46 QALYs with trastuzumab compared
with standard chemotherapy.
The conservative assumption in the analysis was that there
was no further survival benefit after 5 years post-treatment. Nevertheless, the
incremental cost per QALY for the United Kingdom analysis for trastuzumab in
early breast cancer under this conservative assumption was £18,449. This
analysis also assumed that all patients who progressed to metastatic disease
would be treated with trastuzumab again. If this were not the case, then the
incremental cost per QALY was £8,365. It is worthwhile noting that this
analysis did not include any economic gains to society associated with improved
survival of the women in whom recurrences are prevented or delayed. This may be
particularly important because HER2-positive breast cancers are more likely to
affect younger women who can participate in the workforce after successfully
completing their treatment.
The analysis by NICE led to a recommendation for trastuzumab
as a clinically effective and cost-effective treatment option for women with
early stage HER2-positive breast cancer. Only 2 weeks after its licensing in
Europe, a recommendation was made for funding of this indication in the United
Kingdom. It is apparent that this recommendation is based on a careful and
exhaustive appraisal of all the available scientific evidence.
In New Zealand, MEDSAFE granted provisional approval for
trastuzumab in March 2006 and we have yet to hear the outcome of a funding
application made to PHARMAC in December 2005 by the manufacturer.
The issues that have been raised by Rosevear in relation to
the cardiac toxicity of trastuzumab have been carefully considered in the
medical literature5 and can be appropriately managed. The toxicity associated
with trastuzumab is nothing new, as this drug has been available for metastatic
disease in New Zealand since 2001, and the recommendations of Medsafe for
trastuzumab use in early breast cancer deal with this appropriately.6 Such risks
should clearly be the subject of discussion between women and their doctors when
considering treatment with this option.
The public “pressure” for funded access to
trastuzumab in early breast cancer is in fact based on a grass roots campaign,
which was supported by 18,166 New Zealanders.7 This remarkable response was not
the result of a “media campaign” by “well-resourced”
people, as Rosevear incorrectly suggests, but the result of support by ordinary
New Zealanders for a group of women who were forced to advocate for their own
survival. In conclusion, it is unfortunate that the
NZMJ chose to publish such an
ill-informed and confusing piece on such an important issue.
Elisabeth P J
Burgess
Chair Breast Cancer Advocacy Coalition Auckland References and
endnotes:
Martin Rosevear’s responseMy article was one of a series which examined the
‘equity’ of PHARMAC’s funding for a range of new
pharmaceuticals. The intent of these articles is to encourage rational debate
and equity in our funding of health interventions, and we suggested that
Herceptin® is expensive and we questioned whether it is affordable.
In summary:
The letters from Breast Cancer
Advocacy Coalition and Roche raise valid issues on some technical
details.
However the letters are mute on what we understand is the
big issue of budgetary impact and our ability to fund such drugs. If new drugs
such as Herceptin provide better value for money than other health
interventions, then funding should be available to give patients access to these
drugs. We are aware of a number of interventions provided routinely by hospitals
where the $/QALY far exceed an agent such as Herceptin, according to our
understanding, and the mechanisms to re-prioritise DHB funding between these
‘competing’ interventions are very weak. If existing funding
mechanisms are getting in the road of good health governance, these structures
should be changed.
As the respondents point out, the NICE findings suggest
Herceptin is relatively affordable and our understanding of the final NICE
findings is that they quote a base-case of approximately £18k ($55k) per
QALY. However it should be noted that many of the assumptions in these findings
are subject to debate and other interpretations would lower this value to
£8k ($24k) per QALY.
As a result of new information received, I have revised the
cost/benefit analysis in my original article, the details of which are set out
in Figure 1:
Figure 1. Herceptin survival estimates; hypothetical
results
 The model above is simplistic and intended to capture the
major issues in the debate. As we understand them, these issues are:
The life years gained is the area between
the Chemotherapy arm and the options above (Herceptin with declining persistence
and Herceptin with 100% persistence). These results are shown in Figure 2:
Figure 2
*Quality adjusted life
year.
We have chosen to use the results over 20 years as our
base-line results (ignoring the avoidance of metastatic disease):
$31k per QALY (assuming persistent survival) to $58k
per QALY (assuming 10%/annum decline in survival)
This result is lower than our original study. Furthermore we
are aware of clinical developments which may lower these estimates
further:
We agree with the respondents that it is important
for the real benefit of adjuvant Herceptin to be aired. But we also suggest that
it is equally important to understand the challenges in funding these new
treatments, and the need to re-prioritise interventions provided by the wider
health system.
Martin
Rosevear
Director Outcome Management Services (a consultancy specialising in health and public sector economics) Wellington References and
endnotes:
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