Ann Oncol: Intracranial and extracranial efficacy of loratinib in ALK-positive NSCLC patients treated with second-generation TKI

Lorlatinib is an effective brain-penetrating third-generation ALK tyrosine kinase inhibitor (TKI), which has significant anti-tumor activity against ALK-positive non-small cell lung cancer ( NSCLC ).

This study evaluated the overall, intracranial and extracranial efficacy of loratinib for advanced ALK-positive NSCLC after treatment with second-generation ALK TKIs.

In the ongoing phase II study (NCT01970865), patients with ALK-positive advanced NSCLC who had received more than one second-generation ALK TKI±chemotherapy were included in the extended cohort (EXP) based on treatment history.

Among the 139 patients who had been treated with the second-generation ALK TKI (EXP3B-5) for one or more times, 28 patients had received the second-generation ALK TKI (EXP3B) once, and 65 patients had received the ALK TKI (EXP4) twice.

In the cohort of patients treated with EXP3B-5, the ORR (95%CI) was 39.

In the EXP3B treatment cohort, ORR was 42.

In the EXP4-5 treatment cohort, ORR was 38.

Loratinib has clinically significant intracranial and extracranial anti-tumor activity in ALK-positive NSCLC patients who have progressed after the second-generation ALK TKI treatment, and both intracranial and extracranial ORR have increased, especially for patients with fewer previous treatments.

Felip E,Shaw AT,Bearz A et al.