LorlatinibLorviqua
Treatment of patients with Stage IIIB (locally advanced) or Stage IV (metastatic) non-small cell lung cancer (NSCLC) with evidence of an anaplastic lymphoma kinase (ALK) gene rearrangement.
Decisions on record
- Meeting Jul 2021 Deferred ALK-positive non-small cell lung cancer
- Meeting Nov 2019 Recommended Non-small cell lung cancer (NSCLC)
Access path
- TGA registered · Lorviqua
TGA label narrower than the PBS population
- Nov 2019Recommended · restricted
vs alectinib
- Jul 2021Deferred
Comparator changed: alectinib → alectinib (main); brigatinib (supplementary)
- Dec 2021Recommended
- PBS listing · Authority Required
From the public summary
The PBAC deferred making a recommendation for the line-agnostic listing of lorlatinib for the treatment of patients with Stage IIIB (locally advanced) or Stage IV (metastatic) non-squamous or not otherwise specified type non-small cell lung cancer (NSCLC) with evidence of an anaplastic lymphoma kinase (ALK) gene rearrangement in tumour material as the TGA Delegate’s Overview was not available at the time of consideration.PSD · Jul 2021
The PBAC recalled brigatinib received a positive recommendation for a line agnostic PBS listing prior to having a TGA Delegate’s Overview for the first line indication, however considered that, as lorlatinib was currently available on the PBS in the second line setting and there was not an urgent clinical need to list in the first line setting, a deferral was appropriate in the absence of a TGA Delegate’s Overview.PSD · Jul 2021
The submission presented a cost-minimisation analysis (CMA) comparing lorlatinib with alectinib based on the assumption of non-inferiority in terms of effectiveness and safety. The key components and assumptions of the cost-minimisation analysis are summarised below.PSD · Jul 2021
Table 8: Summary of key components and assumptions of the cost-minimisation analysis Component Summary Therapeutic claim: effectiveness Based on evidence presented, effectiveness is assumed to be non-inferior to alectinib Therapeutic claim: safety Based on evidence presented, safety is assumed to be non-inferior to alectinib Evidence base Indirect comparison of randomised trials for the outcomes: OS and PFS Equi-effective doses Lorlatinib 100 mg daily is …PSD · Jul 2021
The submission described lorlatinib as non-inferior to alectinib in terms of both effectiveness and safety.PSD · Jul 2021
Notwithstanding the limitations of indirect comparisons, and noting the potential for confounding from varying follow up durations across the CROWN and ALEX trials, the ESC considered the clinical claim presented in the submission appeared reasonable in terms of PFS. For OS, the evaluation considered the non-inferiority claim could not be substantiated. The data from CROWN were based on an interim analysis and were immature.PSD · Jul 2021
The PBAC noted and welcomed the input from organisations (2) via the Consumer Comments facility on the PBS website. The comments noted the importance of targeted therapies and indicated patients value additional treatment options even if there is no clinical difference between treatments.PSD · Jul 2021
The Medical Oncology Group of Australia (MOGA) also expressed its strong support for the lorlatinib submission, categorising it as one of the therapies of “highest priority for PBS listing” on the basis of the CROWN trial.PSD · Jul 2021
Cost-effectiveness
Cost-minimisation analysis: no ICER calculated. Submission based on cost-minimisation versus alectinib with same proposed pricing as current second-line listing.
The PBAC was of a mind to recommend the Authority Required line-agnostic listing of lorlatinib based on, among other matters, its assessment that the cost-effectiveness of lorlatinib would be acceptable if it were cost-minimised against the least costly alternative therapy. PBAC · 2021
Decision context
PopulationPatients with Stage IIIB (locally advanced) or Stage IV (metastatic) ALK-positive NSCLC who have not previously been treated with an ALK tyrosine kinase inhibitor (TKI).
Risk sharingRSA anticipated for the proposed listing; RSAs currently in place for lorlatinib, alectinib, and brigatinib.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Dec 2021 | Recommended | alectinib (main); brigatinib (supplementary) | — | RCT · PFS |
| Jul 2021 | Deferred | alectinib (main); brigatinib (supplementary) | — | RCT · PFS |
| Nov 2019 | Recommended · restricted | alectinib | — | Single-arm · ORR |
Consumer voice
Two consumer organisations provided input emphasising the importance of targeted therapies and patient preference for additional treatment options. One organisation highlighted adverse events of concern including hypertriglyceridemia, weight gain, fatigue, vision disorders, oedema, anaemia and cognitive effects, while the Medical Oncology Group of Australia expressed strong support for lorlatinib
indicated patients value additional treatment options even if there is no clinical difference between treatments Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to first-line ALK inhibitor-naive patients; TGA label includes both first-line and second-line after prior ALK inhibitors.