Sunitinib malate, capsules, 12.5 mg, 25 mg and 50 mg (base), Sutent®, July 2008
Public summary document for Sunitinib malate, capsules, 12.5 mg, 25 mg and 50 mg (base), Sutent®, July 2008
Page last updated: 31 October 2008
Public Summary Documents
Product:Sunitinib malate, capsules, 12.5 mg, 25 mg
and 50 mg (base), Sutent®
Sponsor: Pfizer Australia Pty Ltd
Date of PBAC Consideration: July 2008
1. Purpose of Application
To seek an Authority required listing for the treatment of
advanced/metastatic renal cell carcinoma (RCC).
To address key uncertainties arising in the evaluation and
assessment from the March 2008 PBAC submission.
2. Background
At the March 2007 meeting, the PBAC deferred consideration of an
authority required listing for renal cell carcinoma pending the
provision of further economic analyses to demonstrate whether the
treatment is acceptably cost effective. The Committee considered
the estimated incremental cost per life year gained over best
supportive care (BSC) provided in the preliminary economic
evaluation in the Pre-PBAC Response was unacceptably high and also
uncertain. (See PBAC Public Summary Document - March
2007)
At the March 2008 meeting, the PBAC rejected the re-submission
based on unacceptably high and uncertain cost effectiveness.
(See PBAC Public Summary Document - March 2008)
The PBAC had a number of concerns with the requested restriction
wording, similar to those identified in the previous consideration
of sunitinib for RCC in March 2007. Treatment should be limited to
clear cell disease as this reflects the trial population and
biological rationale for treatment. “Advanced” is an
ambiguous descriptor of disease status and should be replaced by
Stage IV disease, which, although it would encompass a slightly
wider population with metastatic disease than included in the key
trial, would be more acceptable. WHO performance status should be
less than 2 at initiation.
3. Registration Status
Sunitinib malate was registered by the TGA on 14 September 2006 for the treatment of:
- Advanced renal cell carcinoma;
- Gastrointestinal stromal tumour (GIST) after failure of imatinib mesylate treatment due to resistance or intolerance.
4. Listing Requested and PBAC’s View
Authority required
For the treatment of advanced (unresectable or metastatic) renal
cell carcinoma (RCC) in patients with an ECOG performance status of
0 or 1.
NOTE: It is recommended that treatment with sunitinib be
discontinued if tumour progression occurs.
For PBAC’s view, see Recommendation and
Reasons.
5. Clinical Place for the Proposed Therapy
Renal cell carcinoma is a form of kidney cancer that arises from
the cells of the renal tubule. Sunitinib would provide a treatment
option for patients with advanced RCC.
6. Comparator
The submission nominated placebo (best supportive care) as the main
comparator, which had been previously accepted by the PBAC.
7. Clinical Trials
Reported in the March 2008 PBAC Public Summary Document.
8. Results of Trials
The primary amendments in this submission compared with the March 2008 submission were:
- A decrease in effective price; and
- Correction of the pre- and post progression mortality rates from the previous economic analysis which were noted as underestimating survival.
The submission aimed to address three key issues identified at the
March 2008 meeting as uncertain:
- Progression free survival – treatment effect may taper out in the first few years of treatment;
- Survival mortality rate – was considered in the previous submission to be subject to bias; and
- Adverse events, in particular heart failure.
The submission provided Australia data (from EMBRACE) to address
the cardiovascular safety issue and sensitivity analyses
incorporate the possible impact of heart failure. The submission
also provided a full abstract of the study by Telli et al, and
added in the heart failure rates from this study, from Chu et al
2007, as well as from a paper published by Khakoo (2008).
The submission presented updated survival data from a key efficacy
study (A618-1034), included in the previous submission, to address
the concern that the treatment effect might cease or taper off
beyond the trial period and performed a sensitivity analysis that
used the calculated hazard ratio (HR) for sunitinib versus
interferon-alfa for years 0-2 only, tapering off thereafter so that
the hazard ratio reached 1.0 by year 6, with the HR of 1.0
remaining constant thereafter for the duration of the 10 year
model.
The submission sought to address the uncertainty surrounding
survival by application of a “Landmark Analysis” to
generate mortality rates in the post-progression and
non-progression health states to avoid “guarantee-time
bias” in the survival estimates.
9. Clinical Claim
Reported in the March 2008 PBAC Public Summary Document.
10. Economic Analysis
The submission stated that the economic model previously presented
to the PBAC was essentially unchanged other than addressing areas
of uncertainty surrounding the cost-effectiveness ratio. All areas
of uncertainty previously identified by the PBAC in March 2008 were
addressed by additional analyses undertaken in the
submission.
The submission used the Markov model for the modelled economic
analysis, which was amended by a reduction in the dispensed price
maximum quantity (DPMQ), and used the mortality rates from the
10-weeks Landmark Analysis (10-weeks post randomisation was
selected because it was the time of the first radio-imaging scan
after the first complete dose cycle were assessed for progression;
sensitivity analyses also undertaken for 8-week and 12-week
landmark). The submission estimated the incremental
cost-effectiveness ratio to be in the range of $45,000 –
75,000 per quality adjusted life year (QALY).
For PBAC’s view, see Recommendation and
Reasons.
11. Estimated PBS Usage and Financial Implications
Reported in the March 2008 Public Summary Document.
12. Recommendation and Reasons
The PBAC recommended the listing of sunitinib on the PBS for the
treatment of certain patients with renal cell carcinoma on the
basis of acceptable cost-effectiveness compared with best
supportive care at the new price proposed. As previously, the PBAC
considered that treatment should be limited to Stage IV, clear cell
variant renal cell carcinoma. Patients should also meet the
Memorial Sloan Kettering Cancer Centre (MSKCC) low to intermediate
risk group criteria, have a WHO performance status of 2 or less and
treatment should be as sole PBS-subsidised therapy. The
continuation criteria should be defined by the RECIST criteria as
this would better reflect the population in the clinical
trials.
The PBAC noted that the submission presented an amended modelled
evaluation in which compared to the previous model: the price was
reduced (to be achieved via a risk sharing agreement) and pre- and
post-progression mortality rates were derived from a Landmark
analysis which was conducted to avoid guarantee-time bias in the
survival estimates. The following were explored in sensitivity
analyses to address previous concerns of the PBAC regarding
emerging data on congestive cardiac failure: 7.3% of patients were
allowed to continue the drug despite disease progression and the
percentage of patients who incur hospitalisation costs due to heart
failure was increased from 17.6% to 21.92%. The revised estimated
ICER in the range of $45,000 – 75,000 per QALY was considered
high but robust and acceptable in an area of high clinical need
where no effective alternative treatments are currently
available.
Recommendation
SUNITINIB MALATE, capsules, 12.5 mg, 25 mg and 50 mg (base)
Restriction: Authority required
Initial treatment, as the sole PBS-subsidised therapy, of Stage IV
clear cell variant renal cell carcinoma (RCC) in a patient who
meets the Memorial Sloan Kettering Cancer Centre (MSKCC) low to
intermediate risk group and has a WHO performance status of 2 or
less.
NOTE: No applications for increased maximum
quantities and/or repeats will be authorised.
Maximum quantity: 28
Repeats: 1
Authority required
Continuing treatment beyond 3 months, as the sole PBS-subsidised
therapy, of Stage IV clear cell variant renal cell carcinoma (RCC)
in a patient who has previously been issued with an authority
prescription for sunitinib and who has stable or responding disease
according to RECIST criteria.
NOTE:
RECIST Criteria is defined as follows:
Complete response (CR) is disappearance of all target
lesions.
Partial response (PR) is a 30% decrease in the sum of the longest
diameter of target lesions.
Progressive disease (PD) is a 20% increase in the sum of the
longest diameter of target lesions.
Stable disease (SD) is small changes that do not meet above
criteria.
Authority required (grandfather)
Initial treatment, as the sole PBS-subsidised therapy, of Stage IV
clear cell variant renal cell carcinoma (RCC) in a patient who was
receiving treatment with sunitinib prior to (insert LISTING
DATE).
Maximum quantity: 28
Repeats: 3
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
Pfizer Australia welcomes the positive recommendation of the PBAC
and looks forward to finalising the listing of sunitinib on the PBS
for the treatment of stage IV clear cell variant renal cell
carcinoma.
