Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
2022
INTRODUCTION
The central nervous system (CNS) is a common site of progression among patients with -rearranged lung cancer receiving crizotinib. We conducted a phase 2 study to evaluate the intracranial efficacy of lorlatinib in patients with -rearranged lung cancer who developed CNS-only progression on crizotinib.
METHODS
Patients with metastatic -rearranged lung cancer with CNS-only progression on crizotinib received lorlatinib 100 mg daily. The primary end point was intracranial disease control rate at 12 weeks per modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included intracranial and extracranial progression-free survival, intracranial objective response rate, and safety/tolerability.
RESULTS
A total of 16 patients were enrolled between November 2016 and January 2019. Nine patients (56%) had received prior CNS radiation, with a median of 10.9 months between radiation and lorlatinib. At 12 weeks, the intracranial disease control rate was 100% and intracranial objective response rate was 87%. While on study, the complee intracranial response rate was 60%. With median follow-up of 22 months, seven patients experienced disease progression, including five patients with CNS relapse. The median intracranial and extracranial progression-free survivals were 38.8 months (95% confidence interval: 16.9-not reported) and 41.1 months (95% confidence interval: 17.6-not reported), respectively. Molecular analysis of plasma or tissue from patients with extracranial progression on lorlatinib revealed G2032R (n = 1), L2086F (n = 1), and fusion plus G2032R (n = 1). The safety profile of lorlatinib was consistent with prior studies. There were 11 patients (69%) who required dose reduction, including one patient who discontinued treatment for grade 3 edema. No grade greater than or equal to 4 adverse events were observed.
CONCLUSIONS
Lorlatinib induced durable intracranial responses in patients with -rearranged NSCLC and prior isolated CNS progression on crizotinib.
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