P1.01-101 Survival Benefit of Sequential Therapy in ALK Positive Olioprogressive NSCLC Patients After Crizotinib Resistance

Abstract

Crizotinib is recommended as first-line standard therapy for advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC).Despite initial efficacy of crizotinib, patients ultimately acquired resistance, which leading to tumor progression within one year of crizotinib initiation. However,optimal sequential therapy option among patients with olioprogressive disease remains unknown.Therefore, this study aimed to explore which therapy pattern was advantageous for those patients with extracranial and intracranial metastasis. This retrospective single-center study enrolled 116 Chinese advanced ALK positive NSCLC patients resistant to prior crizotinib treatment,between Jan 2013 and Dec 2016.Based on the site of olioprogressive metastasis, patients were divided into two groups: extracranial (n=57,49.1%) and intracranial (n=59, 50.9%).Sequential therapies mainly included continuation of crizotinib with local therapeutics and next-generation ALK inhibitors. The primary end-point was median overall survival (OS) from the time of crizotinib resistance to death or last follow-up. Among 116 patients,45 patients (38.8%) had died. For extracranial group,26 patients continued crizotinib with local treatment (local radiotherapy or ablation therapy),31 received next-generation ALK inhibitor. Patients followed by next-generation ALK inhibitor beyond crizotinib resistance exhibited a longer OS of 27.6 months than crizotinib continuation with local therapy of 10.8months(p=0.009).Among intracranial group,36 patients continued crizotinib with local treatment including whole brain radiotherapy or stereotactic radiotherapy,23 were next-generation ALK inhibitors users. Continution of crizotinib with local therapy had a non-inferior OS than next-generation ALK inhibitors (28.9 month vs 32.8months, p=0.538) . Next-generation ALK inhibitors had more survival benefit than continuation of crizotinib with local therapy for extracranial olioprogressive patients.While crizotinib continuation with local therapy might be a feasible strategy among patients with intracranial olioprogressive metastasis after crizotinib resistance.