Background: Crizotinib is associated with a favorable survival benefit in patients with ALK-positive non-small cell lung cancer (NSCLC); however, a subset of patients harboring ALK rearrangement shows a poor response.
Methods: We collected the clinical features and survival outcomes of 28 primary-resistant responders (PRR) with progression-free survival (PFS) of < 3 months on crizotinib and compared these with 78 long-term responders (LTR) that achieved > 24 months PFS (control).
Results: Primary resistance was observed in 6.5% of the patients. The median PFS of the PRR and LTR groups was 1.2 months (95% confidence interval [CI] 0.70-1.73) and 47.0 months (95% CI 34.39-59.64), respectively. A better Eastern Cooperative Oncology Group performance status score was significantly associated with longer PFS (odds ratio 0.06, 95% CI 0.01-0.33; P = 0.001). The median overall survival (OS) of the PRR group was 8.4 months (95% CI 3.47-13.42) and crizotinib as first-line treatment was an independent predictive factor for survival outcome (P = 0.005). Patients administered ALK-tyrosine kinase inhibitors after crizotinib progression had significantly longer survival than the PRR group treated with best supportive care (P = 0.007), but no significant difference was found between ALK-tyrosine kinase inhibitor treatment and single chemotherapy (P = 0.944).
Conclusion: Patients with primary resistance to crizotinib displayed unfavorable survival outcomes and the underlying mechanism cannot be identified in clinical features. Nevertheless, next-generation ALK inhibitors and chemotherapy after crizotinib progression could confer a therapeutic and survival benefit in this population.
Keywords: Anaplastic lymphoma kinase; crizotinib; non-small cell lung cancer; primary resistance.
© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.