Lorlatinib in patients with <i>ALK</i>-positive metastatic NSCLC previously treated with an ALK inhibitor: results from a phase IV study

This post-approval study was conducted to confirm efficacy of lorlatinib in anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) that progressed on one prior second-generation ALK tyrosine kinase inhibitor. In this phase IV open-label study, patients with ALK-positive metastatic NSCLC that progressed on first-line alectinib or ceritinib received lorlatinib 100 mg once daily. Primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent central review (ICR). Among 71 patients treated with lorlatinib, 85% had received prior alectinib and 15% received prior ceritinib. Median duration of lorlatinib treatment was 9.7 months. ORR was 42% (95% CI, 31%–55%); median duration of response was not reached. Median progression-free survival was 12.2 months (95% CI, 6.9–22.1). In patients with central nervous system metastases (n = 30), intracranial ORR was 47%. Any-grade treatment-emergent adverse events (TEAEs) occurred in 97% of patients; grade ≥3 occurred in 39%. TEAEs led to dose interruption in 31% and dose reduction in 15% of patients; none discontinued due to treatment-related adverse events. These phase IV efficacy and safety results remained consistent with the pivotal phase I/II study. Lorlatinib continued to show clinically meaningful benefit in patients with previously treated ALK-positive metastatic NSCLC. clinicaltrials.gov identifier is NCT04362072. What is this article about? Non-small cell lung cancer (NSCLC) that has spread to other parts of the body and has changes in a gene called anaplastic lymphoma kinase (ALK) is called ALK-positive metastatic NSCLC. This study was performed after lorlatinib, a third-generation (newer) ALK inhibitor (blocks ALK protein), was approved for treatment of ALK-positive metastatic NSCLC. This study looked at how well lorlatinib works in people who had previously received an older second-generation ALK inhibitor that had stopped working. What were the results? In this study, 71 people with ALK-positive metastatic NSCLC received lorlatinib after receiving a second generation ALK inhibitor (alectinib, 60 people; ceritinib, 11 people). Half of the people received lorlatinib for at least 9.7 months. With lorlatinib treatment, 30 out of 71 people (42%) had their tumors shrink or disappear. Half of the people were alive without their cancer getting worse for at least 12.2 months. Fourteen of the 30 people (47%) with tumors that had spread to the brain before the study began, had their brain tumors brain shrink or disappear. During lorlatinib treatment, 69 out of 71 people (97%) had side effects, and 28 people (39%) had severe or life-threatening side effects. Due to side effects, 22 out of 71 people (31%) paused lorlatinib, 11 people (15%) took a smaller amount. No one completely stopped treatment due to side effects of lorlatinib. What do the results of the study mean? The results showed that people with ALK-positive metastatic NSCLC benefited from lorlatinib treatment.