Bevacizumab, solution for I.V. infusion, 100 mg in 4 mL, 400 mg in 16 mL, Avastin®, July 2008
Public summary document for Bevacizumab, solution for I.V. infusion, 100 mg in 4 mL, 400 mg in 16 mL, Avastin®, July 2008
Page last updated: 31 October 2008
Public Summary Documents
Product: Bevacizumab, solution for I.V. infusion,
100 mg in 4 mL, 400 mg in 16 mL, Avastin®
Sponsor: Roche Products Pty Ltd
Date of PBAC Consideration: July 2008
1. Purpose of Application
The submission sought a Section 100 (Special Authority Program)
listing for the treatment of metastatic colorectal cancer in
patients previously untreated.
2. Background
At the March 2008 meeting, the PBAC rejected a submission for a
section 100 listing for bevacizumab for the treatment of patients
with previously untreated colorectal cancer, and for patients with
disease progression following first-line treatment which includes
bevacizumab, on the grounds of an unacceptably high cost
effectiveness ratio in first line setting only and an unacceptably
high and uncertain cost-effectiveness ratio in combined first and
second line use, and noting the high overall cost to Government
should listing proceed.
(See PBAC Public Summary Document - March 2008)
3. Registration Status
Bevacizumab was registered by the TGA on 2 February 2005 for use in
combination with fluorouracil, folinic acid and irinotecan or
fluorouracil and folinic acid, for the treatment of patients with
metastatic colorectal cancer.
4. Listing Requested and PBAC’s View
SPECIAL AUTHORITY PROGRAM
Section 100 Authority Required
Initial treatment of metastatic colorectal cancer in previously
untreated patients with a WHO performance status of 0 or 1 in
combination with chemotherapy.
Note: Not for use as monotherapy.
Section 100 Authority Required
Continuing PBS-subsidised treatment with bevacizumab plus
chemotherapy in a patient with metastatic colorectal cancer who has
previously been issued with an authority prescription for
bevacizumab and who does not have progressive disease.
Note: Not for use as monotherapy.
Section 100 Authority Required
Initial PBS-subsidised treatment of metastatic colorectal cancer in
a patient with a WHO performance status of 0 or 1 in combination
with chemotherapy:
(1) who had received treatment with bevacizumab prior to the DATE
OF PBS LISTING
(2) who does not have progressive disease.
Note: Not for use as monotherapy.
For PBAC’s view, see Recommendation and
Reasons.
5. Clinical Place for the Proposed Therapy
Bevacizumab would provide additional treatment for patients with
previously untreated metastatic colorectal cancer.
6. Comparator
Reported in the March 2008 PBAC Public Summary Document.
7. Clinical Trials
Reported in the March 2008 PBAC Public Summary Document.
8. Results of Trials
Reported in the March 2008 PBAC Public Summary Document.
9. Clinical Claim
Reported in the March 2008 PBAC Public Summary Document.
10. Economic Analysis
The submission addressed the main matters of concern to the PBAC at
the March 2008 meeting by restricting use to the first line setting
and by providing an updated stepped cost-effectiveness analysis of
bevacizumab.
The submission stated that no changes had been made to the
structure of the economic model, compared with the March 2008
submission.
The modelled economic evaluation estimated the ICER to be in the
range of $45,000 - $75,000 per quality adjusted life year (QALY)
gained assuming either section 100 or section 85 listing.
For PBAC’s view, see Recommendation and
Reasons.
11. Estimated PBS Usage and Financial Implications
The submission estimated the total number of patients associated
with first-line use to be between 10,000 – 50,000.
The total cost to PBS was estimated to be more than $100 million
(using either section 100 or section 85 prices) over 5 years.
12. Recommendation and Reasons
The PBAC noted the following changes to the economic model
considered at the March 2008 meeting: a price decrease, use in the
first-line setting alone, the costs of urinalysis and of treating
adverse events reimbursed by the sponsor, no use beyond progression
in the first line setting, a 5 year time horizon, a different
utility value associated with progressive disease of 0.6, removal
of drug wastage from the calculations, adjustment factors to
calibrate the model against the trial results. These changes to the
model variable resulted in a new base case incremental cost
effectiveness ratio per quality adjusted life year calculated in
the range of $45,000 - $75,000 (using either section 100 or section
85 prices).
The PBAC considered that the addition of bevacizumab to first line
chemotherapy in metastatic colorectal cancer results in clinically
meaningful improvements in survival. The economic model is robust
and although the cost effectiveness ratios are high and depend upon
whether supply is through section 100 or section 85, the only
uncertainty in these estimates arises from the lack of clarity as
to whether the 2008-09 Chemotherapy Budget Measure which is aimed
at eliminating drug wastage, will apply to all bevacizumab
dispensed. If the March 2008 pre-sub-committee response estimates
of wastage are used, the ICER will increase, the cost dependent
upon whether listing is enacted through section 100 or section 85,
respectively.
The PBAC considered that a section 85 listing was more appropriate
for bevacizumab, noting that with a section 85 listing, bevacizumab
would also be eligible for inclusion in section 100 CPAP. A section
100 listing would take longer to implement due to difficulties in
setting up a new program to administer bevacizumab (as it is not
eligible for inclusion in the Highly Specialised Drugs
Program).
Taking these factors into account, PBAC considered that the true
base case ICER would fall in the range of $45,000 – $75,000
(assuming all drug is supplied through section 100 CPAP and all
wastage is eliminated) and in the range of $75,000 - $105,000
(assuming all drug is supplied though section 85 and that wastage
is not eliminated).
The Committee recommended that the PBS restriction for bevacizumab
limit treatment to use in combination with first line chemotherapy
alone. Subsidy should cease upon progressive disease or upon any
change to first-line chemotherapy. No provision should be made to
grandfather patients receiving bevacizumab currently, as any
grandfathering would be associated with an unacceptable risk of use
outside the recommended conditions of PBS-subsidy.
The PBAC recommended that a risk share arrangement be
developed.
Finally, the Committee requested that the Government be advised
that the total cost of subsidising bevacizumab for first line use
in metastatic colorectal cancer is very high at an estimated cost
of greater than $100 million over 5 years.
Recommendation
Authority required
Initial PBS-subsidised treatment, in combination with first-line
chemotherapy, of a patient with previously untreated metastatic
colorectal cancer with a WHO performance status of 0 or 1.
NOTE: Not for use as monotherapy.
Authority Required
Continuing PBS-subsidised treatment, in combination with first-line
chemotherapy, of a patient with metastatic colorectal cancer who
has previously been issued with an authority prescription for
bevacizumab and who does not have progressive disease and who
remains on first line chemotherapy.
NOTE: Not for use as monotherapy.
Maximum quantity: 1 (both strengths)
Repeats: Nil (both strengths)
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be
subsidised in Australia. It considers submissions in this context.
A PBAC decision not to recommend listing or not to recommend
changing a listing does not represent a final PBAC view about the
merits of the medicine. A company can resubmit to the PBAC or seek
independent review of the PBAC decision.
14. Sponsor’s Comment
Roche is very pleased with the decision of the PBAC and will work
in collaboration with the Government to ensure that eligible
patients with metastatic colorectal cancer have access to
bevacizumab in a timely manner.
