ASCO 2024: Long-Term Outcomes With Lorlatinib vs Crizotinib in ALK-Positive NSCLC

By: Joshua D. Madera, MD
Posted: Monday, June 3, 2024

A comparison of the ALK inhibitors lorlatinib and crizotinib was the focus of the phase III CROWN trial in treatment-naive patients with advanced ALK-positive non–small cell lung cancer (NSCLC). After 5 years of follow-up, Benjamin J. Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre, Victoria, Australia, and colleagues reported that the median progression-free survival in the lorlatinib arm has yet to be reached. According to the investigators, this “unprecedented improvement in outcomes” may be the best ever reported in this patient population. These findings, which were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract LBA8503), support the clinical utility of lorlatinib for the management of this type of lung cancer.

A total of 296 patients with advanced ALK-positive NSCLC were recruited for the study. All were treatment-naive. Patients were randomly assigned to receive lorlatinib (n = 149) or crizotinib (n = 147) and closely monitored to assess their clinical outcomes. As of October 2023, 74 of the 149 patients were still receiving lorlatinib, compared with 7 of those given crizotinib.

The study authors reported the median progression-free survival was not reached for patients receiving lorlatinib, and it was 9.1 months for patients receiving crizotinib (hazard ratio [HR] = 0.19). The 5-year progression-free survival was 60% and 8% for patients treated with lorlatinib and crizotinib, respectively. In addition, the median time to intracranial disease progression was 16.4 months with crizotinib and was not reached with lorlatinib (HR = 0.06). Furthermore, evidence of brain disease progression was observed in four patients treated with lorlatinib who had no baseline brain metastases. Moreover, treatment-related adverse events were experienced by 77% of patients treated with lorlatinib and 57% of patients treated with crizotinib.

Disclosure: Disclosure information for the study authors can be found at coi.asco.org.

2024 ASCO Annual Meeting

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