Clinical Summary:

• Design/Population: The phase 3 CROWN trial randomized treatment-naïve patients with advanced ALK-positive NSCLC to receive either lorlatinib or crizotinib, with long-term efficacy and safety assessed after 7 years of follow-up.
• Key Outcomes: After a median follow-up of approximately 7 years, lorlatinib continued to demonstrate substantial long-term progression-free survival benefit compared with crizotinib, with durable systemic and intracranial disease control maintained over time.
• Clinical Relevance: Lorlatinib provides unprecedented long-term systemic and intracranial disease control in first-line ALK-positive NSCLC, supporting its role as a preferred frontline ALK inhibitor with durable benefit despite dose reductions.

According to updated results from the phase 3 CROWN study, lorlatinib sustains long-term benefit among treatment-naïve patients with advanced ALK-positive non-small cell lung cancer (NSCLC). 

These results were presented by Tony Mok, MD, Chinese University of Hong Kong, Hong Kong, China, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this study, 296 patients were randomized to receive either 100 mg of ocne daily lorlatinib (n = 149) or 250 mg of twice daily crizotinib (n = 147). Investigator-assessed efficacy, safety, and biomarker analyses were evaluated. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and safety. 

At analysis, 44% of patients remained on treatment in the lorlatinib arm and 3% of patients remained on treatment in the crizotinib arm. Median PFS remained unreached in the lorlatinib arm and was 9.1 months in the crizotinib arm, with 7-year PFS rates of 55% and 3%, respectively. 

Among patients receiving lorlatinib who remained progression-free at 24 months, the probability of remaining alive without disease progression at 7 years was 79%. PFS benefit with lorlatinib was consistent across all prespecified subgroups, and no new intracranial progression events occurred after the first 30 months of lorlatinib treatment. The median time to intracranial progression remained not reached in the lorlatinib arm and was 16.4 months in the crizotinib arm. OS follow-up remains ongoing, and the required number of events for formal analysis has not been reached. 

The safety profile remained consistent with prior reports. Grade 3/4 adverse events occurred in 77% of patients in the lorlatinib arm and 57% of patients in the crizotinib arm. Treatment-related adverse events leading to permanent discontinuation occurred in 5% and 6% of patients, respectively. No new treatment-related discontinuations were reported after the first 26 months of lorlatinib therapy. Dose reductions occurred in 34% of patients, though long-term efficacy remained similar regardless of dose reduction status.

“With median PFS yet to be reached after 7 yrs of follow up in CROWN, lorlatinib continues to show unprecedented and highly durable benefit in treatment-naïve [patients] with advanced ALK[-positive] NSCLC,” concluded Dr Mok. 

Source:

Mok TS, Solomon BJ, Felip E, et al. Lorlatinib vs crizotinib as first-line treatment for advanced ALK+ non-small cell lung cancer: 7-year update from the phase 3 CROWN study. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 8502.