LarotrectinibVitrakvi
Recommended OncologyRestricted 💬 consumer voice
Treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) or soft tissue sarcoma (STS) harbouring neurotrophic tropomyosin receptor kinase (NTRK) gene fusions.
4
Submissions
3 resub
2020–24
On the record
Redacted
ICER range
commercial-in-confidence
Redacted
Cost basis
Decisions on record
- Meeting Mar 2024 Recommended Non-small cell lung cancer (NSCLC) or soft tissue sarcoma (STS) with NTRK gene fusions
- Meeting Mar 2023 Withdrawn Solid tumours harbouring neurotrophic receptor tyrosine kinase (NTRK) gene fusions no PSD
- Meeting Mar 2022 Recommended Solid tumours harbouring neurotrophic receptor tyrosine kinase gene fusions
- Meeting Nov 2021 Deferred NTRK fusion tumours (paediatric and adult populations)
- Meeting Dec 2020 Not recommended Solid tumours harbouring neurotrophic receptor tyrosine kinase (NTRK) gene fusions no PSD
- Meeting Nov 2020 Deferred Solid tumours harbouring neurotrophic receptor tyrosine kinase (NTRK) gene fusions
Access path
- TGA registered · Vitrakvi
TGA label narrower than the PBS population
- Dec 2020Not recommended
vs Standard of care (SoC)
- Nov 2021Deferred
Comparator changed: Standard of care (SoC) → standard of care (SoC) — specific therapies…
- Mar 2022Recommended · restricted
Comparator changed: standard of care (SoC) — specific therapies vary by tumour type and…
- Mar 2024Recommended · restricted
Comparator changed: standard of care (SoC) → docetaxel (NSCLC); pazopanib (STS)
- PBS listing · Restricted
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
The PBAC recommended the Authority Required listing of larotrectinib for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) or soft tissue sarcoma (STS) harbouring neurotrophic tropomyosin receptor kinase (NTRK) gene fusions. The PBAC noted patients with NSCLC and STS have access to gene panel testing that includes NTRK fusions on the Medicare Benefits Schedule (MBS).PSD · Mar 2024
The PBAC noted the input from health care professionals and organisations which highlighted the need for additional treatment options for rare cancers.PSD · Mar 2024
Economic analysis
The resubmission presented separate modelled economic evaluations for the use of larotrectinib in NTRK-positive, locally advanced and unresectable, or metastatic, NSCLC and STS and was based on descriptive indirect comparisons of non-matched single arms from heterogeneous studies. This was changed from the previous 28PSD · Mar 2024
The types of economic evaluation presented were a cost-effectiveness analysis and cost-utility analysis with outcomes measured in terms of life-years (LYs) gained and quality-adjusted life years (QALYs) gained. This was unchanged from the previous submissions. The key components of the economic evaluation are summarised in Table 12.PSD · Mar 2024
Clinical claim
The resubmission described larotrectinib as superior in terms of effectiveness and with a comparable safety profile compared with SoC in the proposed population with NSCLC or STS.PSD · Mar 2024
The ESC considered the claim of superior effectiveness was not adequately supported by the evidence presented in the resubmission. Collectively, the following limitations engender a high degree of uncertainty regarding the magnitude of the incremental 27PSD · Mar 2024
Consumer comments
Omico and Lung Foundation Australia emphasised the need for novel targeted therapies such as larotrectinib to be available to patients with rare or less common cancers. In addition to describing the effectiveness of larotrectinib for NSCLC, the organisations highlighted the opportunity to match therapy with the characteristics of individual patients, and avoid unnecessary treatments and associated side effects.PSD · Mar 2024
The MOGA expressed its strong support for the larotrectinib submission, categorising it as one of the therapies of “highest priority for PBS listing” on the basis of the SCOUT and NAVIGATE trials. The PBAC noted that the MOGA presented a European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) for larotrectinib, which was limited to 3 (out of a maximum of 5, where 5 and 4 represent the grades with substantial improvement)9.PSD · Mar 2024
Cost-effectiveness
ICERs exceeded $95,000 to <$115,000/QALY gained; specific numeric values not stated in public text.
ICER uncertain ×2ICER / price too highEconomic model disputedImmature survival dataNo head-to-head trial
Decision context
PopulationAdults with locally advanced or metastatic NSCLC or STS harbouring confirmed NTRK gene fusions.
Why it was knocked back
- small patient numbers across studies (NSCLC n=25, STS n=30), immature overall survival data, evidence restricted to refractory setting not applicable to proposed line-agnostic listing, concerns about standard of care comparators and their applicability to early-line setting, claim of superiority based on descriptive indirect comparisons not sufficiently supported, high and uncertain ICER
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2024 | Recommended · restricted | docetaxel (NSCLC); pazopanib (STS) | — | Single-arm · ORR |
| Mar 2022 | Recommended · restricted | standard of care (SoC) | — | Single-arm · ORR |
| Nov 2021 | Deferred | standard of care (SoC) — specific therapies vary by tumour type and treatment line | — | Single-arm · ORR |
| Dec 2020 | Not recommended | Standard of care (SoC) | — | Single-arm · ORR |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| LOXO-TRK-14001 | Ph 1 | 75 | Number of participants with adverse events | completed |
Codependent tests
| Service | Biomarker | MSAC outcome | Year |
|---|---|---|---|
| NTRK gene fusion testing (FISH and NGS) | NTRK gene fusion (NTRK1, NTRK2, NTRK3) | not supported | 2020 |
Consumer voice
Three organisations (Omico, Lung Foundation Australia, and MOGA) supported PBS listing of larotrectinib for adults with locally advanced or metastatic NSCLC or STS with NTRK gene fusions. They emphasised the need for novel targeted therapies for rare cancers and highlighted the ability to personalise therapy while avoiding unnecessary treatments and side effects.
Omico and Lung Foundation Australia emphasised the need for novel targeted therapies such as larotrectinib to be available to patients with rare or less common cancers. Consumer comments · PSD
unmet needaccess barriersrare diseaseside effectspersonalised medicine
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to NSCLC or STS only; TGA label covers all solid tumours with NTRK fusions.