P3.02a-020 Clinical Failure to Crizotinib in Patients with Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancers: Topic: ALK Clinical

Abstract

Crizotinib, as the standard treatment for use in first-line treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC), showed superiority over platinum-based chemotherapy in advanced ALK-positive lung adenocarcinoma. Undoubtedly, the resistance to crizotinib is a current bottleneck which limits its clinical application. However, there are few reports about clinical failure to crizotinib, especially the correlation between the failure patterns of crizotinib and survival benefit. Totally, 171 ALK-positive NSCLC patients treated with crizotinib were reviewed at the Guangdong General Hospital in China from October 2010 to July 2016. The status of ALK rearrangement was assessed by Lysis ALK Break Apart fluorescence in situ hybridization, reverse transcription polymerase chain reaction, or Ventana ALK immunohistochemistry. Chi-square test and Kapla-Meier survival curve were used to analyze the results statistically. Among enrolled patients, 47.5% (81/171) gained secondary resistance, 10.5% (18/171) had primary resistance and 4 patients stopped taking crizotinib because of the occurrence of unacceptable toxicities including anasarca, ventricular tachycardia and hepatic insufficiency. Moreover, 49 patients had no progression, in which 2 patients had taken crizotinib more than 5 years uninterruptedly. In the patients with secondary resistance (n=81), 46 were male and 63 were never smokers. Brain metastases occurred in 27.1% (22/81) at the baseline, half of which (11/22) still had brain progression after the treatment of crizotinib. On the contrary, 21 patients without brain metastases at the baseline were evaluated at disease progression because of brain metastases. We classified patients with secondary resistance into several categories according to the failure patterns of crizotinib, such as dramatic, gradual and local progression. There were 47 (58.0%), 2 (2.5%) and 32 (39.5%) patients for dramatic, gradual and local progression respectively. The patients with dramatic progression had an inferior progression-free survival with crizotinib to those with gradual and local progression (9.8 vs 11.9 months), which did not achieve statistical significance. The post progression survival (PPS) of dramatic progression group is 10.4 months. The PPS of other group is 20.5 months comparatively. Patients with dramatic progression showed shorter overall survival when compared with other patients (26.7 vs 41.0 months, P=0.042). Dramatic progression was prevalent in ALK-positive lung adenocarcinoma beyond failure to crizotinib, and predicted poor overall survival.