On November 2nd 2018, lorlatinib (LORBRENA®, Pfizer) received accelerated approval by the FDA for the second- and third-line treatment of patients with metastatic, anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC). Third-line patients should have had progression on crizotinib and another ALK-inhibitor for metastatic disease, and second-line patients should have had progression on either alectinib or ceritinib in the first-line for metastatic disease.

Study B7461001

The Phase I/II non‑randomised, dose-ranging and activity-estimating, multi‑cohort, multicenter study B7461001 (NCT01970865) included a subgroup of 215 ALK-positive metastatic NSCLC patients pretreated with one or more ALK-inhibitors. The Phase II part’s major efficacy measures included the overall response rate (ORR) and intracranial ORR (RECIST 1.1) by independent review committee (IRC).

A 48% (95% CI, 42-55) ORR was observed, which included 4% complete (CR) and 44% partial responses (PR) with an estimated median response duration of 12.5 months (95% CI, 8.4-23.7). In the 89 patients with measurable central nervous system lesions, 21% CR and 38% PR were observed, resulting in an intracranial ORR by RECIST 1.1 of 60% (95% CI, 49-70). The estimated median intercranial response duration was 19.5 months (95% CI, 12.4-not reached).

Safety

Common adverse reactions that occurred ≥20% in patients treated with lorlatinib included oedema, peripheral neuropathy, cognitive effects, dyspnoea, fatigue, weight gain, arthralgia, mood effects, and diarrhoea. Hypercholesterolaemia and hypertriglyceridaemia were the most common laboratory abnormalities.

LORBRENA® full prescribing information