Cabazitaxel, injection set containing 1 single use vial concentrate for I.V. infusion, 60 mg (anhydrous) in 1.5 mL with diluent, Jevtana® - November 2011
Page last updated: 02 March 2012
Public Summary Document
Product: Cabazitaxel, injection set containing 1
single use vial concentrate for I.V. infusion, 60 mg (anhydrous) in
1.5 mL with diluent, Jevtana®
Sponsor: Sanofi-Aventis Pty Ltd
Date of PBAC Consideration: November 2011
1. Purpose of Application
The submission sought an Authority Required listing for treatment
of hormone refractory metastatic carcinoma of the prostate (mHRPC)
in patients previously treated with a docetaxel containing
regimen.
2. Background
At the July 2011 meeting, the PBAC rejected a submission for
cabazitaxel for an Authority Required listing for the treatment of
hormone refractory metastatic carcinoma of the prostate in a
patient previously treated with a docetaxel containing regimen on
the basis of a high and uncertain cost-effectiveness ratio.
For full details refer to the July 2011 Public Summary
Document.
3. Registration Status
On 8 December 2011, cabazitaxel was TGA registered for the
following indication:
In combination with prednisone or prednisolone is indicated for the
treatment of patients with hormone refractory metastatic prostate
cancer previously treated with a docetaxel containing
regimen.
4. Listing Requested and PBAC’s View
Authority Required
Treatment of hormone refractory metastatic carcinoma of the
prostate in a patient previously treated with a
docetaxel-containing regimen.
The requested listing was unchanged, refer to July 2011 Public
Summary Document.
5. Clinical Place for the Proposed Therapy
Refer to July 2011 Public Summary Document.
6. Comparator
The comparator was unchanged, refer to July 2011 Public Summary
Document.
7. Clinical Trials
The clinical trials were unchanged, refer to July 2011 Public
Summary Document.
8. Results of Trials
To address the PBAC’s concerns from July 2011, the submission
further analysed the clinical trial data.
The submission stated that no changes were made to the
extrapolations for survival due to the relatively high proportion
of benefit captured within trial and the good fit of the Weibull
curve to the observed data.
The submission stated that most of the survival benefit attributed
to cabazitaxel in the economic evaluation was observed during the
clinical trial period (“within-trial”). With
approximately 75% of the survival benefit captured within the trial
(3.18 months/4.26 months ≈ 0.75) and therefore 25% of the
survival benefit for cabazitaxel was derived from beyond the trial
period (1.08 months/4.26 months).
The submission agreed with the PBAC (from July 2011) that most of
the gain with cabazitaxel is spent on the progressive disease state
in the terminal or end of life phase of the disease with increased
toxicity.
Of the 4.26 months overall survival advantage:
• 74% (3.14 months) is spent in the end of life phase
(progressive disease)
• 17% (0.74 months) is spent free of progression but with
toxicities and
• the remaining 9% (0.38 months) is spent free of progression
and free of toxicity.
For PBAC’s view, see Recommendation and
Reasons.
9. Clinical Claim
The clinical claim was unchanged, refer to July 2011 Public
Summary Document.
10. Economic Analysis
The submission offered an updated price proposal and provided an
updated economic evaluation which tested the impact of wider use of
G-CSF based on the TROPIC trial.
The revised base case incremental cost per extra quality adjusted
life year (QALY) gained was estimated to be in the range of $45,000
and $75,000.
The submission stated that the utility values used in the July 2011
submission, particularly for the progressive disease health state,
are lower – and therefore more conservative – than has
been reported elsewhere. The submission stated that the utility
values have not been updated for this re-submission, although a
sensitivity analysis using the NICE utility values was included.
When the utility values, as derived using the EQ-5D from the Early
Access Program (EAP) were used, the ICER was reduced to the range
of $15,000 and $45,000 per extra QALY.
For PBAC’s view, see Recommendation and
Reasons.
11. Estimated PBS Usage and Financial Implications
The submission presented no updated information.
12. Recommendation and Reasons
The PBAC noted that the updated price proposal for cabazitaxel gave
an estimated base case ICER between $45,000 – $75,000, which
the PBAC still considered was unacceptably high. The PBAC agreed
that use of the costs of G-CSF from the TROPIC trial was
appropriate, however, the ICER, if used in all cycles and in all
patients was estimated to between $75,000 – $105,000, which
is unacceptably high.
In July 2011, the PBAC considered that most of the survival gain
with cabazitaxel was beyond the trial period and was based on time
spent in the terminal or end of life phase of the disease with
increased toxicity. The PBAC noted that no changes had been made to
the extrapolation of survival in the resubmission and that 25% of
the survival benefit for cabazitaxel was captured from beyond the
trial period (1.08 m/4.26 m), which was a mean and not median
value. However, the PBAC considered that the survival benefit was
still a source of uncertainty, especially in light of the high ICER
and that most of the mean overall survival gain of 4.26 months is
spent in the progressive disease state (3.14 months). The PBAC
recalled that when considering docetaxel for PBS listing for
hormonal refractory metastatic prostate cancer, the greatest
proportion of the 3.73 months gain in extrapolated mean overall
survival was spent in the TWIST state (no toxicity and no
progression) and that this was an important consideration in the
recommendation to list docetaxel.
The PBAC agreed that the utility values used in the submission were
conservative and acceptable.
The PBAC considered that a new price proposal would be necessary
for the ICER to be acceptable.
The PBAC therefore rejected the submission on the basis of a high
and uncertain cost-effectiveness ratio
The PBAC also acknowledged and noted the consumer comments on this
item.
Recommendation:
Reject
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
Sanofi is disappointed by this decision but is committed to continuing to work with the PBAC to ensure that Jevtana is made available on the PBS for Australian men who have prostate cancer.
