Dabrafenib + Trametinib
Adjuvant treatment for patients with BRAF V600 mutation positive, completely resected Stage III melanoma.
Decisions on record
- Meeting Mar 2025 Recommended Non-small cell lung cancer (NSCLC) with BRAF V600E mutation, advanced or metastatic
- Meeting Mar 2024 Recommended Paediatric glioma (BRAF V600E mutation positive low grade and high grade)
From the public summary
7.1 The PBAC deferred making a decision regarding the listing of dabrafenib plus trametinib as adjuvant treatment for BRAF V600 mutation positive patients with completely resected Stage III melanoma. In deciding to defer, the PBAC acknowledged that there was a high unmet clinical need for effective therapies to reduce the risk of recurrence for patients with resected Stage III melanoma.PSD · Mar 2019
7.2 The PBAC acknowledged the consumer comments, which were supportive of the PBS listing. In particular, the PBAC noted comments that there are no available PBS- subsidised adjuvant treatment options for melanoma, that dabrafenib+trametinib are oral agents, and that side effects range from mild to severe, but are manageable. 32PSD · Mar 2019
6.43 The submission presented a modelled economic evaluation, based on the COMBI-AD trial. The type of economic evaluation presented was a cost-effectiveness analysis and 21PSD · Mar 2019
Table 14: Summary of model structure and rationale Component Summary Time horizon '''''' years in the model versus 52 monthsa in the COMBI-AD clinical trial Outcomes LYs and QALYs Methods used to Cohort analysis using a partitioned survival approach generate results Health states Three health states: RFS, recurrent disease and death Cycle length 1 month The proportion of patients in each health state was determined from the RFS and OS curves.PSD · Mar 2019
6.36 The submission described dabrafenib+trametinib as superior in terms of RFS and OS, but inferior in terms of safety to placebo.PSD · Mar 2019
6.37 The submission’s claim that dabrafenib+trametinib was superior to placebo in terms of RFS for adjuvant treatment of completely resected Stage III, BRAF V600 mutation positive melanoma, was reasonable, based on the evidence presented in COMBI-AD.PSD · Mar 2019
6.2 The PBAC noted and welcomed the input from individuals (45), health care professionals (1) and organisations (4) via the Consumer Comments facility on the PBS website and other correspondence. The comments described a range of benefits of treatment with dabrafenib+trametinib adjuvant therapy including manageable adverse events, the ease of oral administration, and also a reduction in stress and anxiety for patients with no other adjuvant therapy …PSD · Mar 2019
6.3 The PBAC noted the correspondence received from Melanoma Patients Australia (MPA) supporting the listing. MPA also provided a summary of individual patient comments, describing the benefits of reduced risk of recurrence and treatment efficacy and the need for equitable access and choice of treatments.PSD · Mar 2019
Cost-effectiveness
ICER values are redacted in the PSD; pricing marked as commercially sensitive ('***' and 'Effective' price redacted).
Decision context
PopulationPatients with completely resected Stage IIIB, IIIC or IIID melanoma with BRAF V600 positive mutations and WHO performance status of 1 or less, requiring adjuvant treatment within 12 weeks of complete resection for a maximum of 12 months.
Risk sharingA special pricing arrangement (SPA) was proposed with an effective price reduction at the ex-manufacturer level (percentage redacted).
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2019 | Deferred | routine follow-up (clinician visits and radiological imaging) | — | RCT · Relapse-free survival |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| COMBI-AD | Ph 3 | 870 | Percentage of Participants With Relapse-free Survival (RFS) Events | completed |
Consumer voice
Consumer input from 45 individuals, healthcare professionals, and patient organisations (including Melanoma Patients Australia and Melanoma Consumers Alliance) supported listing of dabrafenib+trametinib adjuvant therapy, highlighting manageable adverse events, ease of oral administration, reduced recurrence risk, and the importance of equitable treatment access and choice.
The comments described a range of benefits of treatment with dabrafenib+trametinib adjuvant therapy including manageable adverse events, the ease of oral administration, and also a reduction in stress and anxiety for patients with no other adjuvant therapy options available. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to Stage IIIB/C/D with performance status ≤1 and treatment within 12 weeks; TGA allows any lymph node involvement post-resection.