Vemurafenib + Cobimetinib
Recommended · restricted OncologyAuthority RequiredFirst-line line 💬 consumer voice
Treatment of BRAF V600 mutation positive unresectable or metastatic melanoma as first-line therapy.
1
Submissions
1 resub
2016–16
On the record
—
ICER range
Cost-min
Cost basis
risk sharing
Access path
- Mar 2016Recommended · restricted
vs dabrafenib + trametinib
- PBS listing · Authority Required
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
7.1 The PBAC recommended the Authority Required (STREAMLINED) listing of vemurafenib in combination with cobimetinib, for the treatment of BRAF V600 mutation positive unresectable or metastatic melanoma, on a cost-minimisation basis against dabrafenib + trametinib at an equi-effective dose of vemurafenib 960 mg twice daily + cobimetinib 60 mg once daily (Days 1−21 of each 28 cycle) versus dabrafenib 150 mg twice daily + trametinib 2 mg once daily.PSD · Mar 2016
7.2 The proposal to use vemurafenib + cobimetinib in BRAF mutation positive patients, following failure of immunotherapy was rejected by the PBAC on the basis that the sponsor failed to provide sufficient evidence of clinical benefit following failure of immunotherapy.PSD · Mar 2016
Economic analysis
6.19 The submission presented a cost-minimisation analysis based on the indirect comparison of vemurafenib + cobimetinib compared to dabrafenib + trametinib.PSD · Mar 2016
6.20 The equi-effective doses were estimated as: vemurafenib 960 mg twice daily + cobimetinib 60 mg once daily (Days 1−21 of each 28 cycle) and dabrafenib 150 mg twice daily + trametinib 2 mg once daily. The cost-minimisation approach was based on the published approved ex-manufacturer price (AEMP) and was derived from a calculation of the equivalent costs per day and reflected the different periods of supply per dispensing.PSD · Mar 2016
Clinical claim
6.13 The submission described vemurafenib + cobimetinib as clinically non-inferior to dabrafenib + trametinib. In terms of comparative safety, the submission stated that 10PSD · Mar 2016
6.14 The claim of non-inferior comparative effectiveness was partially supported, for the following reasons: While the indirect comparisons demonstrated no statistically significant differences between vemurafenib + cobimetinib compared to dabrafenib and trametinib for PFS and OS, there was no discussion or establishment of an appropriate non-inferiority margin by the submission.PSD · Mar 2016
Financial management – risk sharing
6.29 The submission acknowledged that Special Pricing Arrangements apply to dabrafenib + trametinib and stated that the submission was lodged on the basis of price parity, in principle, for the combination therapies (ie the effective price of the individual components may vary, but the effective combination prices will be aligned).PSD · Mar 2016
The submission also acknowledged that the sponsor would be required to share the existing Risk Share Arrangement caps under the Deed of Agreement previously agreed to by the sponsor of dabrafenib + trametinib.PSD · Mar 2016
Cost-effectiveness
Cost-minimisation analysis; no ICER calculated by design.
The PBAC recommended the Authority Required (STREAMLINED) listing of vemurafenib in combination with cobimetinib, for the treatment of BRAF V600 mutation positive unresectable or metastatic melanoma, on a cost-minimisation basis against dabrafenib + trametinib at an equi-effective dose of vemurafenib 960 mg twice daily + cobimetinib 60 mg once daily (Days 1−21 of each 28 cycle) versus dabrafenib 150 mg twice daily + trametinib 2 mg once daily. PBAC · 2016
Cost-effectiveness accepted
Decision context
PopulationAdults with previously untreated BRAF V600 mutation positive unresectable Stage III or Stage IV metastatic melanoma, with WHO performance status of 2 or less, not previously treated with PBS subsidised BRAF inhibitor therapy or with documented intolerance to another BRAF inhibitor.
Risk sharingRisk Share Arrangement (RSA) with dabrafenib + trametinib sponsor required to ensure no additional cost to Government beyond current financial caps.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2016 | Recommended · restricted | dabrafenib + trametinib | — | RCT · PFS |
Clinical evidence
Consumer voice
No consumer comments were received for this item.
The PBAC noted that no consumer comments were received for this item. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to first-line therapy in previously untreated patients; TGA label permits any line of treatment without prior therapy limitation.