Abstract
Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib.At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months.Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.
Highlights
The anaplastic lymphoma kinase (ALK) gene is rearranged in approximately 5% of non-small-cell lung cancer (NSCLC) cases, leading to constitutive activation of the ALK tyrosine kinase domain and tumorigenesis [1, 2]
Crizotinib is an inhibitor of ALK kinase activity that has demonstrated its superiority over conventional chemotherapy in advanced ALK-positive non-smallcell lung cancer (NSCLC) [3, 4]
Following expanded access program (EAP) discontinuation, 104 additional ALK-positive patients treated with crizotinib as second-line approved drug were enrolled
Summary
The anaplastic lymphoma kinase (ALK) gene is rearranged in approximately 5% of non-small-cell lung cancer (NSCLC) cases, leading to constitutive activation of the ALK tyrosine kinase domain and tumorigenesis [1, 2]. Crizotinib was compared to standard first-line and second-line chemotherapy in two randomized Phase III trials (PROFILE 1014 and PROFILE 1007), achieving higher response rates and a significantly longer median progression-free survival (PFS) [3, 4]. It is approved worldwide for treating advanced ALK-positive NSCLC. In the PROFILE 1007 trial comparing crizotinib to pemetrexed or docetaxel as second-line following platinum-based regimen failure, an updated survival analysis showed a median OS with crizotinib at 21.7 months but identified no difference in OS between the crizotinib arm and chemotherapy arm, probably due to a cross-over in the chemotherapy arm [6]. Another limitation comes from the restrictive inclusion criteria implemented in clinical trials, meaning any benefit observed in a selected population might not reflect that in daily practice
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