Efficacy and Safety of ALK Tyrosine Kinase Inhibitors in Elderly Patients with Advanced ALK-Positive Non-Small Cell Lung Cancer: Findings from the Real-Life Cohort.

Little is known regarding the anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) efficacy and safety in the elderly. Consecutive patients (n = 53) with ALK-positive advanced non-small cell lung cancer treated with an ALK TKI were identified through internal databases of three cancer centers and divided into groups A (< 65 years old; n = 34) and B (≥65 years old; n = 19). Progression-free survival (PFS), ALK TKI safety and overall survival (OS) were assessed. Uni- and multivariate PFS and OS analyses were performed. Crizotinib, ceritinib, and alectinib were administered in 94 and 100%, 35 and 31%, 38 and 52% of patients in groups A and B, respectively. The median PFS (months) was 5.4 (95% CI, 3.4-12.4) and 5.6 (95% CI, 2.5-14.7) with crizotinib (log-rank 0.0009, p = 0.9), 4.7 (95% CI, 1.0-11.5) and 23.0 (95% CI, 0.8-27.7) with ceritinib (log-rank 0.44, p = 0.5), and 21.2 (95% CI, 1.2 to not reached, NR) and 5.6 (95% CI, 0.5 to NR) with alectinib (log-rank 0.53, p = 0.5) in groups A and B, respectively. The median OS (months) comprised 29.8 (95% CI, 21.0 to NR) and 25.1 (95% CI, 10.8-53.6) in groups A and B, respectively (log-rank 0.57, p = 0.4). Age affected neither PFS nor OS. 19 and 37%, 50 and 40%, and 0 and 0% of patients in groups A and B, treated with crizotinib, ceritinib, and alectinib, respectively, developed high-grade adverse events. The treatment discontinuation rate was 9 and 21%, 16 and 60%, 0 and 0% with crizotinib, ceritinib, and alectinib in groups A and B, respectively. In the elderly, crizotinib, ceritinib, and alectinib treatments are associated with similar efficacy but different safety profiles; alectinib is associated with a lower rate of high-grade adverse events and a lower treatment discontinuation rate.

Bedas A ，Peled N ，Maimon Rabinovich N ，Mishaeli M ，Shochat T ，Zer A ，Rotem O ，Allen AM ，Bar J ，Dudnik E ，On behalf of the Israel Lung Cancer Group ... -  《-》

Treatment Sequencing in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer in Japan: A Real-World Observational Study.

Goto Y ，Yamamoto N ，Masters ET ，Kikkawa H ，Mardekian J ，Wiltshire R ，Togo K ，Ohe Y ... -  《-》

A retrospective study of alectinib versus ceritinib in patients with advanced non-small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed.

Kuo CS ，Tung PH ，Huang AC ，Wang CC ，Chang JW ，Liu CY ，Chung FT ，Fang YF ，Guo YK ，Yang CT ... -  《BMC CANCER》

Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC.

Zhu Q ，Hu H ，Weng DS ，Zhang XF ，Chen CL ，Zhou ZQ ，Tang Y ，Xia JC ... -  《BMC CANCER》

The efficacy and safety of ALK inhibitors in the treatment of ALK-positive non-small cell lung cancer: A network meta-analysis.

The current study was carried out to compare the effectiveness and safety of different ALK inhibitors in treating ALK+ NSCLC. Progression-free survival (PFS), disease control rate (DCR), overall response rate (ORR), and intracranial ORR and DCR have been aggregated to appraise the effectiveness of each ALKi. The discontinuation rate due to adverse events (AEs) was pooled to evaluate their safety. Bayesian network meta-analyses were used to compare the ORR, DCR, PFS, and discontinuation rate of patients treated with alectinib, ceritinib, crizotinib, and chemotherapy. Compared with chemotherapy, ALK inhibitors significantly prolonged PFS [hazard ratio (HR) and 95% confidence interval (CI): alectinib, 0.50 (0.43-0.58); ceritinib, 0.75 (0.69-0.83); crizotinib, 0.71 (0.66-0.76)]. The ORRs were significantly higher for ALK inhibitors than for chemotherapy [odds ratio (OR) and corresponding 95% CI: alectinib, 11.69 (4.29-36.56); ceritinib, 7.85 (3.44-19.27); crizotinib, 6.04 (3.33-11.71)]. The discontinuation rates were lower for ALK inhibitors than for chemotherapy [OR and corresponding 95% CI: alectinib, 0.42 (0.12-1.36); ceritinib, 0.52 (0.20-1.35); crizotinib, 0.70 (0.30-1.62)]. ALK+ NSCLC patients treated with ALKi tend to have longer PFS than those treated with chemotherapy. ALKi-naïve patients tended to response better than their ALKi-pretreated counterparts. Alectinib appeared to be preferable for treating brain metastases due to its high intracranial efficacy. Patients treated with alectinib or ceritinib tended to have higher ORR and DCR than patients with similar baselines treated with crizotinib or chemotherapy. No significant differences in discontinuation rate were found for alectinib, ceritinib, crizotinib, and chemotherapy.

Fan J ，Fong T ，Xia Z ，Zhang J ，Luo P ... -  《Cancer Medicine》