Efficacy and safety analysis of lorlatinib for ALK-positive advanced NSCLC: a multicentre real-world study in China.

Background: Lorlatinib, a third-generation Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKI), has demonstrated excellent curative effect in clinical studies to overcome mutations resistant to first- and second-generation ALK-TKIs. It also has improved blood-brain barrier crossing and reduced brain metastases.

Methods: 44 patients were selected who received Lorlatinib as initial treatment for first-diagnosis ALK-positive non-small-cell lung cancer (NSCLC) or who received Lorlatinib as a back-line treatment after developing resistance with first- and second-generation ALK-TKIs. The primary study endpoints are objective response rate (ORR) and disease control rate (DCR).

Results: For the 44 patients, the overall ORR[95% confidence intervals (CI)]was 59% (95% CI: 51-69), the DCR was 93% (95% CI: 36-56). In the first-line treatment group(n = 15), lorlatinib showned an ORR 93% (95% CI: 52-81), and the DCR was 100% (95% CI: 47-78). Additionally, 29 patients who received sequential Lorlatinib after progression on at least one first- or second-generation ALK-TKI showned an ORR of 41% (95% CI: 41-63) and a DCR of 90% (95% CI: 20-40). Lorlatinib demonstrated strong intracranial efficacay, with an overall intracranial objective response rate (IC-ORR) of 74% (95% CI: 67-92) and an intracranial disease control rate (IC-DCR) of 96% (95% CI: 53-81) in 23 patients with brain metastase. Among them, the IC-ORR and IC-DCR of 7 patients who received Lorlatinib as first-line therapy were both 100% (95% CI: 89-103). For 16 patients who had received at least one ALK-TKI, the IC-ORR with Lorlatinib was 63% (95% CI: 51-90), and the IC-DCR was 94% (95% CI: 27-70). 44 patients treated with Lorlatinib, all at a starting dose of 100 mg/day, 77% experienced adverse events, with the most common associated adverse event being hyperlipidaemia, However the overall grading was mild to moderate, with only one case of a reduction in dosage to 75 mg.

Conclusions: This real-world evidence demonstrates that Lorlatinib exhibits significant clinical efficacy and intracranial anti-tumor activity in the treatment of ALK + NSCLC patients, whether in first-line or post-first-line treatment, while being well tolerated.