Abstract
PurposeAlthough most patients with ALK-positive non?small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2).Materials and MethodsData on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients’ PFS2 time was assessed after adjusting for potential confounding factors.ResultsWith initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not (P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2.DiscussionThis study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib.
Highlights
Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2
Among the patients with ALK-positive non‒small-cell lung cancer (NSCLC) treated at our institution, 33 received continued crizotinib therapy after Response Evaluation Criteria in Solid Tumors (RECIST)-defined disease progression
In this study of 33 patients who received continued crizotinib therapy after RECIST-defined disease progression, the objective response rate (ORR) and initial progression-free survival (PFS) time (PFS1) were consistent with those reported in phase 1-3 clinical trials of crizotinb monotherapy in patients with ALK-positive lung cancer[7, 8, 11]
Summary
Lung cancer with a both high morbidity and mortality [1], is a heterogeneous disease in different patients as various driven-gene been identified [2,3,4,5].Certain patients (e.g., those with adenocarcinoma histology, EGFR wild type, non/light-smokers, younger age) have rates of ALK rearrangements that approach 30%, and this group could benefit from the use of ALKinhibitor treatment with crizotinib, a small molecule, multi-targeted tyrosine kinase inhibitor (TKI) [6].A phase 1 study of crizotinib has shown it to have a clinical marked effect in the treatment of advanced non‒small-cell lung cancer (NSCLC) patients with ALK-EML4 rearrangement www.impactjournals.com/oncotarget and other ALK gene rearrangements, with an objective response rate (ORR) of 60.8% and a progression-free survival (PFS) time of 9.7 months [7]. The PROFILE 1014 study in ALK-positive lung cancer patients demonstrated that crizotinib can increase PFS and ORR in comparison with first-line platinum-based agents [8]. Patients with ALK-positive NSCLC may benefit from crizotinib, most develop progressive disease (PD). A retrospective analysis of the clinical benefits of continuing crizotinb beyond initial PD (CBPD) concluded that a longer overall survival was achieved in patients with advanced ALK-positive NSCLC [9]. The National Comprehensive Cancer Network (NCCN) clinical guideline recommends the resumption of crizotinb therapy when patients with disease progression do not have multiple systemic symptomatic lesions
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