Clinical Benefit Of Continued Therapy With Crizotinib Beyond Initial Disease Progression In Advanced Alk Positive Nsclc

Abstract Background: ALK-positive advanced NSCLC patients treated with crizotinib typically progress after initial tumor response. However, most patients continue crizotinib beyond RECIST-defined Progressive disease (PD) if they are clinically benefiting from it. Methods: We screened 53 patients whose tumors harbor ALK rearrangement, and identified 32 patients received crizotinib as initial ALK inhibitor between 2010 and 2013. Baseline characteristics, response, sites of initial progression, efficacy of continuation therapy with crizotinib beyond PD, PFS, and OS were analyzed. Results: Among 32 patients who received crizotinib, 14 (43%) were male, median age was 43 (range: 21-66), 15 (47%) were never-smokers, 23 (72%) were stage IV at diagnosis. All patients had ECOG PS of 0/1 before treatment with crizotinib. Four patients without progression have received crizotinib. All 32 patients were radiologically evaluated. 21 patients achieved an objective response (65%): two patients had a complete response and 19 had a partial response. Disease control (ie, complete response, partial response, or stable disease) was achieved by 27 patients. Median PFS and OS were 168 days (range: 28-837) and 525 days (range: 45-1238), respectively. The most common sites of disease progression in these population were brain (n = 10), lung (n = 3), and bone (n = 3). Among 28 patients who had PD, 18 continued crizotinib treatment beyond PD, including ten patients with only isolated CNS metastasis, one with metastases in both the CNS and primary lesion, and seven with metastasis at non-CNS sites only. The patients who continued crizotinib beyond PD tend to be longer survival from the time of PD. Conclusion: Patients who continued treatment with crizotinib beyond PD were more likely to have isolated CNS metastasis. The present study suggested that continuation of treatment with crizotinib after PD may provide survival benefit to ALK positive patients.