← The record

Encorafenib; Binimetinib

Recommended OncologyAuthority RequiredFirst-line line 💬 consumer voice

Treatment of unresectable or metastatic melanoma with a BRAF V600 mutation. The combination is indicated for adult patients with unresectable Stage III or Stage IV malignant melanoma positive for BRAF V600 mutation.

1
Submissions
2018–18
On the record
ICER range
Cost-min
Cost basis
risk sharing

Decision on record

1 decision
  • Meeting Nov 2025 Recommended Non-small cell lung cancer with BRAF V600E mutation – metastatic NSCLC in treatment-naïve patients

Access path

1 submission · public record
  1. Nov 2018
    Recommended · restricted

    vs dabrafenib+trametinib (primary); vemurafenib+cobimetinib…

  2. PBS listing · Authority Required
RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
PBAC outcome
7.1 The PBAC recommended the Authority Required (STREAMLINED) listing of encorafenib in combination with binimetinib, for the treatment of BRAF V600 mutation positive unresectable Stage III or Stage IV metastatic melanoma, on a cost- minimisation basis against dabrafenib+trametinib and vemurafenib+cobimetinib.PSD · Nov 2018
7.2 The PBAC acknowledged the input provided by individuals, health care professionals and organisations describing the clinical benefits and consumer demand for encorafenib+binimetinib in patients with BRAF V600 mutation-positive cutaneous melanoma.PSD · Nov 2018
Economic analysis
6.30 The submission presented a cost-minimisation analysis based on the indirect comparisons of encorafenib+binimetinib with dabrafenib+trametinib and with vemurafenib+cobimetinib. The ESC considered that a cost-minimisation analysis was appropriate.PSD · Nov 2018
6.31 The submission’s proposed equi-effective doses for encorafenib+binimetinib versus dabrafenib+trametinib and versus vemurafenib+cobimetinib were:  Encorafenib 450 mg once daily + binimetinib 45 mg twice daily, and  Dabrafenib 150 mg twice daily + trametinib 2 mg once daily, or  Vemurafenib 960 mg twice daily + cobimetinib 60 mg once daily (21 days on-treatment plus 7 days off-treatment, in a 28-day cycle).PSD · Nov 2018
Clinical claim
6.26 The submission described encorafenib+binimetinib as at least non-inferior in terms of effectiveness and safety compared with dabrafenib+trametinib and vemurafenib+cobimetinib.PSD · Nov 2018
6.27 The ESC noted that there was uncertainty regarding the non-inferiority claim of encorafenib+binimetinib relative to dabrafenib+trametinib and vemurafenib+cobimetinib, both in terms of effectiveness and safety as:  This claim relied on common reference-adjusted indirect comparisons of the COLUMBUS, COMBI-V, COMBI-D and coBRIM trials.PSD · Nov 2018
Consumer comments
6.2 The PBAC noted and welcomed the input from individuals (6), health care professionals (6) and organisations (3) via the Consumer Comments facility on the PBS website. The consumer comments described a range of benefits of treatment with encorafenib+binimetinib including fewer side effects and prolonged survival.PSD · Nov 2018
6.4 The Medical Oncology Group of Australia (MOGA) also expressed its support for the encorafenib+binimetinib submission, on the basis of phase III clinical evidence. The PBAC noted that the MOGA considered that encorafenib+binimetinib appeared less toxic than the comparators based on evidence presented in the COLUMBUS trial.PSD · Nov 2018

Cost-effectiveness

Cost-minimisation analysis performed; no ICER calculated as equi-effectiveness was demonstrated.

The PBAC noted these would need to be updated based on the effective prices. PBAC · 2018
Economic model disputedPrice cut / RSA needed

Decision context

PopulationAdult patients with unresectable Stage III or Stage IV malignant melanoma with BRAF V600 mutation, WHO performance status 0–2, treatment-naïve or intolerant to another BRAF inhibitor.

Risk sharingRisk Sharing Arrangement (RSA) currently in place for the comparators (dabrafenib+trametinib and vemurafenib+cobimetinib); special pricing arrangements apply to encorafenib and binimetinib.

Submission history

1 entries
DecidedOutcomeComparatorICEREvidence
Nov 2018 Recommended · restricted dabrafenib+trametinib (primary); vemurafenib+cobimetinib (secondary) RCT · PFS

Consumer voice

Nov 2018

Consumer input described benefits of encorafenib+binimetinib treatment including fewer side effects and prolonged survival. Professional organizations supported access for unresectable or metastatic melanoma with BRAF V600 mutation, noting reduced toxicity compared to comparators.

The consumer comments described a range of benefits of treatment with encorafenib+binimetinib including fewer side effects and prolonged survival. Consumer comments · PSD
side effectssurvival benefittreatment burdenaccess barriersunmet need

Similar precedents

By decision profile

Regulatory · TGA

Label narrower than PBS population — PBAC restricts to first-line treatment, WHO performance status 0–2, and treatment-naïve or BRAF inhibitor-intolerant patients; TGA label has no such restrictions.