Trametinib
Recommended OncologyAuthority RequiredFirst-line line 💬 consumer voice
Treatment of unresectable or metastatic melanoma in patients with BRAF V600 mutation, in combination with dabrafenib or as monotherapy in patients with intolerance to BRAF inhibitors.
3
Submissions
2 resub
2014–16
On the record
$45k–75k
ICER range
2 sourced ICERs · 2014–2016
ICER stated
Cost basis
risk sharing
Decisions on record
- Meeting Jul 2016 Recommended Melanoma
- Meeting Nov 2014 Recommended 500 microgram tablet, 30 2 mg tablet, 30 Mekinist® GlaxoSmithKline Australia Pty Ltd New listing (Major submission) Melanoma To provide further information to support a request for a managed entry scheme to allow the listing of trametinib as an Authority Required listing for the treatment of patient
- Meeting Mar 2014 Not recommended Mekinist® GlaxoSmithKline Australia Pty Ltd Melanoma To request Authority Required General Schedule listing of trametinib for use, in combination with dabrafenib for the treatment of patients with BRAF V600 mutation positive unresectable stage III or metastatic (stage IV) melanoma. Sponsor Comment:
Access path
- Mar 2014Not recommended
Immature OS data, unreliable estimate of treatment effect, robust basis for subsidy recommendation not established…
- ↻ resubmittedNov 2014Recommended · restricted
- Jul 2016Recommended · restricted
- PBS listing · Authority Required
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
7.1 The PBAC recommended continuation of the Authority required listing of trametinib, for use in combination with dabrafenib, for the treatment of patients with BRAF V600 mutation positive unresectable stage III or metastatic (stage IV) malignant melanoma. 21PSD · Jul 2016
7.2 The PBAC recalled that, in recommending the listing of trametinib in November 2014, it had proposed to review the finalised results of COMBI-D and COMBI-V trials, to make sure patients receiving medicines on the PBS are being treated according to the best available evidence and that the cost of the combination therapy remains justified in terms of acceptable cost-effectiveness.PSD · Jul 2016
Economic analysis
6.24 The submission presented a cost-utility analysis based on pooled individual patient data from BRF113220, COMBI-D and COMBI-V, as specified by the PBAC in November 2014 (November PSD, paragraph 5.11). The table below provides a summary of the model structure. 13PSD · Jul 2016
Outcomes QALYs and life-years Kaplan-Meier curves generated from the IPD analysis are used up to median duration of Methods used to follow-up, and then the log-logistic extrapolation of pooled BRF113220, COMBI-D and generate results COMBI-V PFS and OS data is used.PSD · Jul 2016
Clinical claim
6.18 The submission concluded that combination trametinib and dabrafenib therapy is superior to dabrafenib monotherapy with respect to efficacy and has a different but no worse comparative safety profile.PSD · Jul 2016
6.19 This claim of superior comparative effectiveness had already been considered reasonable by the PBAC (November 2014 PBAC Minutes, paragraph 6.18), and the premise of this submission had been to establish the magnitude of incremental effect.PSD · Jul 2016
Consumer comments
6.1 The PBAC noted the input from health care professionals (2) and organisations (1) via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with trametinib including ability to return to work and suggestions on the use of trametinib. The PBAC noted the advice received from Medical Oncology Group of Australia Incorporated (MOGA) clarifying the likely use of trametinib in clinical practice.PSD · Mar 2014
Financial management – risk sharing
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Cost-effectiveness
The PBAC considered that the structure of the model was reasonable, but the inputs used from the BRF113220 trial did not provide a robust basis for making a subsidisation recommendation. PBAC · 2016
ICER uncertainEconomic model disputed ×2
Decision context
PopulationAdults with unresectable stage III or metastatic (stage IV) BRAF V600 mutation-positive melanoma, in combination with dabrafenib, or as monotherapy in patients with intolerance to BRAF inhibitors.
Risk sharingManaged Entry Scheme (MES) with rebate arrangement: if the clinical benefit of trametinib modelled from BRF113220 fails to be realised in final COMBI-D and COMBI-V results, sponsor rebates Commonwealth by price reduction multiplied by script numbers between listing and price reduction date, with interest applied.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2016 | Recommended · restricted | dabrafenib monotherapy | $45k–75k | RCT · OS |
| Nov 2014 | Recommended · restricted | dabrafenib monotherapy | $45k–75k | RCT · PFS |
| Mar 2014 | Not recommended | dabrafenib monotherapy | — | RCT · PFS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| COMBI-V | Ph 3 | 704 | Overall Survival (OS) | completed |
Codependent tests
| Service | Biomarker | MSAC outcome | Year |
|---|---|---|---|
| BRAF V600 testing in Stage III melanoma | BRAF V600 mutation | supported | 2019 |
Consumer voice
Healthcare professionals and organisations provided input describing benefits of trametinib treatment, including ability to return to work. Medical Oncology Group of Australia Incorporated clarified the likely use of trametinib in clinical practice.
The comments described a range of benefits of treatment with trametinib including ability to return to work and suggestions on the use of trametinib. Consumer comments · PSD
quality of lifereturn to worktreatment benefitclinical practice guidance
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to first-line treatment; TGA label does not specify treatment line.