LORVIQUA (lorlatinib)

Key points

Approval for reimbursement in the treatment of adult patients with ALK (anaplastic lymphoma kinase) positive advanced non-small cell lung cancer (NSCLC) not previously treated with an ALK inhibitor, as monotherapy.

Therapeutic improvement?

LORVIQUA (lorlatinib) provides a therapeutic advance over crizotinib, along with alectinib and brigatinib, in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with an ALK rearrangement (ALK positive).

Role in therapeutic strategy?

In NSCLC with an ALK mutation, management has been transformed by the arrival of anti-ALK targeted therapy, the first example of which was crizotinib, which has shown superiority over systemic chemotherapy. Other anti-ALK TKIs were subsequently developed (ceritinib, alectinib, brigatinib). According to the latest AURA guidelines of 2022, given the demonstrated superiority over crizotinib in terms of progression-free survival, alectinib (ALECENSA), brigatinib (ALUNBRIG) and lorlatinib (LORVIQUA) are preferred options in the first-line treatment of ALK+ lung cancer

Role of LORVIQUA (lorlatinib) in the therapeutic strategy:

Lorlatinib is an additional therapeutic option for the first-line treatment of ALK+ advanced NSCLC.

Like alectinib and brigatinib, its superiority over crizotinib has been demonstrated only in terms of progression-free survival. In view of the available data, its role compared to these molecules still needs to be specified. However, the choice of an anti-ALK drug as the first-line treatment should take into account the level of evidence for each molecule and its tolerance profile. In this context, alectinib has a demonstrated effect on brain metastases.

Furthermore, the conditions of use may be discussed in case of sensitivity of the mutation to the molecule (as determined by phenotyping of resistance mechanisms by "liquid biopsy" or in situ sampling), and following consideration of the benefit/tolerance ratio of each molecule.