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Published on: September 18, 2013
Feasibility and Efficacy of Lorlatinib in Japanese Patients With Relapsed/Refractory ALK-Aberrant Neuroblastoma
Takashi Imazu1, Hirohito Kubota1, Satoshi Saida1
1Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Abstract:
Lorlatinib, a third-generation ALK inhibitor, was administered off-label to five heavily pretreated patients with relapsed or refractory ALK-aberrant neuroblastoma. ALK alterations included F1174L, R1275Q, BEND5::ALK fusion, and ALK amplification; three patients had MYCN amplification. Best responses were three partial responses and two disease progressions. The longest progression-free survival (6.7 months) occurred in a patient with F1174L and non-amplified MYCN, whereas rapid progression was observed in two MYCN-amplified cases. Lorlatinib was generally well tolerated with manageable adverse events. These findings suggest that lorlatinib is a feasible therapeutic option in ALK-aberrant neuroblastoma and that clinical heterogeneity in treatment response warrants further investigation.
Insights
Lorlatinib shows promise for ALK-aberrant neuroblastoma, offering partial responses in some heavily pretreated patients. However, MYCN amplification may predict poorer outcomes, highlighting the need for further research.
Area of Science:
- Oncology
- Pediatric Cancer Research
- Pharmacology
Background:
- Neuroblastoma is a pediatric cancer with poor prognosis, especially in relapsed or refractory cases.
- Anaplastic Lymphoma Kinase (ALK) alterations are implicated in neuroblastoma development and progression.
- Targeting ALK is a therapeutic strategy for ALK-aberrant cancers.
Purpose of the Study:
- To evaluate the efficacy and safety of off-label lorlatinib in heavily pretreated patients with relapsed or refractory ALK-aberrant neuroblastoma.
- To explore the impact of specific ALK alterations and MYCN amplification on treatment response.
- To assess the tolerability of lorlatinib in this patient population.
Main Methods:
- Retrospective analysis of five heavily pretreated neuroblastoma patients.
- Administration of lorlatinib, a third-generation ALK inhibitor, off-label.
- Characterization of ALK alterations (F1174L, R1275Q, BEND5::ALK fusion, ALK amplification) and MYCN status.
- Assessment of objective response and progression-free survival.
Main Results:
- Three partial responses and two disease progressions were observed.
- The longest progression-free survival was 6.7 months in a patient with F1174L and non-amplified MYCN.
- Two patients with MYCN amplification experienced rapid disease progression.
- Lorlatinib was generally well-tolerated with manageable adverse events.
Conclusions:
- Lorlatinib represents a feasible therapeutic option for patients with ALK-aberrant neuroblastoma.
- Clinical heterogeneity in treatment response suggests that factors like MYCN amplification influence outcomes.
- Further clinical investigation is warranted to optimize lorlatinib use and understand response determinants.