Impact of crizotinib on long-term survival of ALK-positive advanced non-small-cell lung cancer: A Chinese multicenter cohort study.

Puyuan Xing,Li Liang,Hongge Liang,Li Shan,Qiang Wang,Yang Du,Junling Li,Mengzhao Wang,Di Ma,Zhaohui Zhang,Xuezhi Hao,Yan Wang,Tao Xin

doi:10.21147/j.issn.1000-9604.2019.03.10

Abstract

ObjectiveCrizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALK-positive advanced NSCLC. MethodsWe reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors (RECIST)-defined progressive disease (PD). ResultsA total of 428 eligible ALK-positive NSCLC patients were enrolled, 273 (63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival (PFS) and overall survival (OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval (95% CI), 12.4−16.4] months and 53.4 (95% CI, 33.7−73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate (DCR) and a longer median OS compared with second-/later-line crizotinib treatment (94.8% and OS not reachedvs. 89.0% and 40.5 months, respectively). For 261 patients with RECIST-defined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease (CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival. ConclusionsThis study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.

Highlights

Anaplastic lymphoma kinase (ALK) gene rearrangements are found in approximately 3%−7% of non-small-cell lung cancer (NSCLC) patients [1], with a higher incidence (9.7%) in the Chinese population [2]
A total of 484 patients were enrolled for data collection, and 428 with advanced ALK-positive NSCLC met the inclusion criteria (Supplementary Figure S1)
OS, overall survival; ECOG PS, Eastern Cooperative Oncology Group performance status; PFS, progression-free survival; NA, not available; CBPD, crizotinib beyond progressive disease; ALK, anaplastic lymphoma kinase; HR, hazard ratio; 95% CI, 95% confidence interval

Summary

Introduction

Anaplastic lymphoma kinase (ALK) gene rearrangements are found in approximately 3%−7% of non-small-cell lung cancer (NSCLC) patients [1], with a higher incidence (9.7%) in the Chinese population [2]. Crizotinib is a firstgeneration inhibitor of ALK-kinase activity and it has demonstrated superiority over conventional chemotherapy in advanced ALK-positive NSCLC in a series of PROFILE clinical trials [3,4,5,6,7]. The phase III PROFILE 1014 study had established the role of first-line crizotinib therapy for newly diagnosed ALK-positive NSCLC patients, and its updated survival analysis reported a survival probability at 4 years of 56.6% [11]. Real-world investigations on the survival outcomes of different sequencing therapies are still needed to inform the optimal treatment after progressive disease (PD) on crizotinib

Methods

Results

Conclusion