A large, single‐center, real‐world study of clinicopathological characteristics and treatment in advanced ALK‐positive non‐small‐cell lung cancer

Abstract

Crizotinib has achieved astonishing success in advanced non‐small‐cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, no real‐world studies described the clinicopathological characteristics and treatment of such patients in China. Patients were consecutively collected from Sun Yat‐sen University Cancer Center. Chi‐square test was applied to explore the relationship between ALK fusion status and metastasis sites. Kaplan–Meier methods and multivariable analyses were used to estimate progression‐free survival (PFS). A total of 291 advanced NSCLC patients (ALK (+), N = 97; both ALK & epidermal growth factor receptor (EGFR) (‐), N = 194) were enrolled. The occurrence of brain metastasis in ALK‐positive patients was significantly higher than double‐negative ones both at baseline (26.5% vs. 16.5%, P = 0.038) and during treatment (25.8% vs. 11.9%, P = 0.003), but opposite for pleural effusion (6.2% vs. 26.9%, P < 0.001 at baseline; 3.1% vs. 10.3%, P = 0.031 during treatment). ALK‐positive patients of 53.6% used crizotinib, whereas others only received chemotherapy (37.1%) or supportive care (9.3%). Usage of crizotinib prolonged PFS compared with chemotherapy in ALK‐positive patients (median PFS 17.6 m vs. 4.8 m, P < 0.001). ALK‐positive NSCLC had more brain metastasis and less pleural effusion than double‐negative ones. Crizotinib showed better PFS than chemotherapy in advanced ALK‐positive NSCLC at any line. However, half advanced ALK‐positive patients never received crizotinib, which was grim and need improving.

Treatment duration as a surrogate endpoint to evaluate the efficacy of crizotinib in sequential therapy for patients with advanced ALK‐positive non‐small cell lung cancer: A retrospective, real‐world study

“…Our findings are consistent with the outcomes of previously published retrospective studies . It showed that the median PFS1 of crizotinib was 13.2 months, and the median TD of crizotinib among CBPD patients was 39.7 months.…”

“…Multiple‐covariate Cox regression analysis revealed that CBPD remained significantly associated with improved OS after adjusting for relevant factors. In real‐world studies, the reported median PFS of crizotinib treatment has ranged from 13.3 to 17.6 months . Liu et al reported that crizotinib continuation beyond the RECIST‐defined PD was feasible in clinical practice.…”

A real‑world study of treatment patterns and survival outcome in advanced anaplastic lymphoma kinase‑positive non‑small‑cell lung cancer

“…Notably, the PFS of patients receiving crizotinib as the initial therapy (median PFS, 18.5 months) was longer compared with the PFS results of the PROFILE 1014 (median PFS, 10.9 months) and PROFILE 1029 (median PFS, 11.1 months) trials. A similar PFS result (median PFS, 17.6 months) was reported in another real-world study from a single center in China (22). In the previous clinical trials (10,11), brain and bone scanning was repeated every 12 weeks to monitor for new lesions in the follow-up schedule.…”

Front‐line treatment of ceritinib improves efficacy over crizotinib for Asian patients with anaplastic lymphoma kinase fusion NSCLC: The role of systemic progression control

“…Crizotinib, the first FDA‐approved ALKi for the treatment of advanced ALK‐positive NSCLC, has shown superior efficacy compared to the standard of care chemotherapy docetaxel and pemetrexed‐cisplatin doublet in the second‐ and first‐line setting, respectively . Disease progression usually occurs around 10 to 12 months during crizotinib treatment where the pattern of progression involves a high frequency of brain metastasis which targets the brain as a sanctuary site . This finding can be partly attributed to the drug transporters located at the blood brain barrier that actively efflux the therapeutic drugs and thereby reduce their concentrations in the brain tissue .…”