Triptorelin Embonate, powder for injection and 1 vial solvent 2 mL, 3.75 mg (1 month) and 11.25 mg (3 month) (base), Diphereline November 2006
Public summary document forTriptorelin Embonate, powder for injection and 1 vial solvent 2 mL, 3.75 mg (1 month) and 11.25 mg (3 month) (base), Diphereline
Page last updated: 02 March 2007
Public Summary Document
Product: Triptorelin Embonate, powder for injection and 1 vial solvent 2 mL, 3.75
mg (1 month) and 11.25 mg (3 month) (base), Diphereline
Sponsor: Ipsen Pty Ltd
Date of PBAC Consideration: November 2006
1. Purpose of Application
The submission sought an Authority Required PBS listing for locally advanced or metastatic carcinoma of the prostate.
2. Background
This drug had not previously been considered by the PBAC.
3. Registration Status
Triptorelin embonate was registered by the TGA on 28 August 2006 for the treatment of locally advanced or metastatic prostate cancer.
4. Listing Requested and PBAC’s View
Authority required
Locally advanced (equivalent to Stage C) or metastatic (equivalent to Stage D) carcinoma
of the prostate.
The PBAC noted the requested restriction was consistent with those for other medicines
currently listed on the PBS for this condition.
5. Clinical Place for the Proposed Therapy
Prostate cancer localised within the prostate gland can be treated successfully with
surgery to remove the prostate or radical radiotherapy. However, 30% of those patients
will later on develop metastatic disease. Endocrine therapy, which includes the blockade
of androgen receptors (anti-androgen therapy) and indirect inhibition of the biosynthesis
of androgen (gonadotrophin releasing hormone (GnRH) agonist therapy), is the first
and primary means of treatment for patients with metastatic prostate cancer.
Triptorelin is a long acting GnRH agonist, which results in a desensitisation phenomenon
by which gonadotrophin secretion is dramatically reduced, resulting in gonadal suppression,
in men, and a marked decrease in testosterone production.
6. Comparator
The submission nominated goserelin acetate as the main comparator. The minor comparator was leuprorelin. The PBAC considered both comparators appropriate.
7. Clinical Trials
The submission presented an indirect comparison of triptorelin acetate (three randomised
trials) and goserelin acetate (two randomised trials) via the common reference of
orchiectomy or pulpectomy (partial orchiectomy for cosmetic reasons).
These trials had been published at the time of submission, as follows:
Triptorelin versus orchidectomy
|
Trial/First author |
Protocol title |
Publication citation |
|---|---|---|
|
Ipsen Clinical Study 914 CL 17E |
Decapeptyl in the treatment of advanced prostatic cancer: comparative study with pulpectomy |
Therap Progress in Urological Cancers 1989 pages 53-60 |
|
Ipsen Clinical Study 914 CL 7P |
Long term experience in the treatment of advanced prostate cancer with decapeptyl, in comparison to orchiectomy |
Acta Urologica Belgica 1988 56(4) 581-588 |
|
Ipsen Clinical Study 914 CL 14P |
Orchiectomy versus long-acting D-TRP-6-LHRH in advanced prostate cancer |
Brit J Urology 1987 59: 248-254 |
|
Parmar et al |
Medical or surgical orchiectomy? |
Brit Med J 1991, 302:1272 |
Goserelin versus orchidectomy
|
Trial/First author |
Protocol title |
Publication citation |
|---|---|---|
|
Kaisary AV et al |
Comparison of LHRH analogue (Zoladex) with orchiectomy in patients with metastatic prostatic cancer |
Brit J Urology 1991 67: 502-508 |
|
Vogelzang NJ et al |
Goserelin versus orchiectomy in the treatment of advanced prostate cancer: Final results of a randomised trial |
Urology 1995 46: 220-226 |
Triptorelin embonate versus leuprorelin acetate
|
Trial/First author |
Protocol title |
Publication citation |
|---|---|---|
|
Ipsen study DEB 96-TRI-01 (Phase II) Heyns CF et al |
Comparative efficacy of triptorelin embonate and leuprorelin acetate in men with advanced prostate cancer |
BJU International 2003 92: 226-231 |
8. Results of Trials
Trial data for death and overall survival time were measured in weeks from therapy
initiation to patient’s death, regardless of additional therapeutic measures taken
during or after the 2-year treatment period. Both the fixed and random effects pooled
absolute risk and relative risk estimates identified no statistically significant
difference between goserelin, triptorelin and orchiectomy in terms of mortality.
A reanalysis conducted during the evaluation of the submission to estimate the indirect
comparison of triptorelin versus goserelin found that there was no difference in the
relative risk of death between goserelin and triptorelin.
Pharmacodynamic and pharmacokinetic studies provided in the submission were evaluated
for absorption and testosterone level control. Despite inadequate information in some
of the studies to assess baseline comparability and significant differences in the
extent and rate of absorption between the two formulations (embonate and acetate),
they were equivalent in terms of pharmacodynamics as assessed by testosterone serum
levels. There was no evidence of an accumulative effect.
In the trials, the most commonly reported adverse events were hot flushes, bone pain,
headache and musculoskeletal pain. Toxicity and adverse events seem to be comparable
between triptorelin and goserelin.
For PBAC’s comments on these results, see Recommendation and Reasons.
9. Clinical Claim
The submission described triptorelin as having equal effectiveness and toxicity with
goserelin and other GnRH agonists.
This description was considered by the PBAC to be reasonable, based on the supporting
data.
10. Economic Analysis
The submission presented a preliminary economic evaluation using a cost-minimisation
approach. The resources included were drug costs.
A modelled economic evaluation was not presented.
The equi-effective doses in the context of cost-minimisation were triptorelin embonate
3.75 mg once monthly, for duration as necessary, and goserelin acetate 3.6 mg once
monthly for duration as necessary.
11. Estimated PBS Usage and Financial Implications
12. Recommendation and Reasons
The PBAC recommended listing on a cost minimisation basis with goserelin acetate with
the equi-effective doses being triptorelin embonate (Diphereline) 3.75mg once monthly,
for duration as necessary, and goserelin acetate (Zoladex) 3.6mg once monthly for
duration as necessary; and triptorelin embonate (Diphereline), 11.25mg once every
three months, for duration as necessary, and goserelin acetate (Zoladex), 10.8mg once
every three months for duration as necessary. The equi-effective doses are based on
the key trials of triptorelin and goserelin versus orchiectomy as the common reference,
and pharmacodynamic studies showing equivalence in terms of serum concentrations of
testosterone between triptorelin acetate and triptorelin embonate for which listing
is proposed.
The PBAC noted that the submission based its claim of non-inferiority with goserelin
acetate on a series of clinical trials dating from the late 1980s and early 1990s
and that these trials were conducted with less rigour than is the case currently.
However the Committee was satisfied that non-inferiority had been established. The
PBAC further noted that triptorelin embonate and goserelin acetate belong to the same
pharmacological group of gonadotropin releasing hormone agonists and this gives extra
support for a cost-minimisation listing.
The PBAC recommended the 20 day safety net rule should apply.
Recommendation
Triptorelin Embonate, powder for injection and 1 vial solvent 2mL, 3.75 mg (1 month)
and 11.25 mg (3 month) (base)
Restriction: Authority required
Locally advanced (equivalent to Stage C) or metastatic (equivalent to Stage D) carcinoma
of the prostate.
Maximum quantity: 1
Repeats: 5 (3.75 mg) and 1 (11.25 mg)
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
The sponsor has no comment.
