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
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Favorable predictors for survival in advanced ALK-positive non-small cell lung cancer patients beyond crizotinib resistance.
Crizotinib has demonstrated favorable efficacy in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). Unfortunately, the majority of ALK-positive patients ultimately develop acquired resistance within one year after the initiation of crizotinib treatment; however, the estimation of overall survival (OS) beyond crizotinib resistance has not yet been fully demonstrated. The purpose of this study was to identify favorable predictors affecting survival outcome.
In this single-center retrospective study, the data of 136 patients with advanced ALK-positive NSCLC beyond crizotinib resistance were analyzed between January 2013 and December 2017. Patients were divided into two groups according to intracranial or extracranial progression on crizotinib, and sequential therapies including crizotinib continuation with local therapy, next-generation ALK inhibitors, and chemotherapy. The primary endpoint was the median OS duration from the start of crizotinib resistance to death or the last follow-up. Univariate and multivariate Cox analyses of OS were carried out.
At the time of analysis, 60 (41.1%) of the 136 patients had died. Median progression free survival (PFS) and OS from the metastatic diagnosis were 10.4 and 41.3 months, respectively. Sequential therapies administered beyond crizotinib treatment were: next-generation ALK inhibitors (54 patients), chemotherapy (20 patients), and crizotinib continuation with local therapy (62 patients). Multivariate Cox analysis revealed that long PFS with crizotinib (≥ 10.4 months), intracranial progression, and next-generation ALK inhibitors were significantly associated with a decreased risk of death.
Long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next-generation ALK inhibitors might be favorable predictors for OS in advanced ALK-positive NSCLC patients.
Xu H
，Yang G
，Yang L
，Yang Y
，Ma D
，Li J
，Hao X
，Xing P
，Wang Y
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Clinical observation of crizotinib in the treatment of ALK-positive advanced non-small cell lung cancer.
ALK is a prognostic and predictive tumor marker in non-small cell lung carcinoma (NSCLC), and is more often found in lung adenocarcinomas.
The clinical and pathological data of 87 patients confirmed to have NSCLC by pathology or cytology were selected from April 2014 to January 2017 at the Tumor Hospital of Hebei Province.
Of the 87 ALK-positive-patients, 47 patients were treated with oral administration of crizotinib. The objective response rate (ORR) was 61.7%, the disease control rate (DCR) was 93.6%, and the mPFS was 19 months. In an analysis of the number of metastatic sites, the patients who had more than three metastatic sites, the ORR, DCR, and mPFS were 63.9%, 94.5%, and 19 months, compared with the 45.5%, 91%, and 11 months in the patients with less sites (P = 0.040). For patients of 60 years or older, ORR and DCR were 40% and 100%, the other group was 71.9% and 90.6%, respectively(P = 0.036). The timing of treatment was analyzed. At the first application of crizotinib, ORR and DCR were 78.2% and 100% corresponding 45.8% and 87.5% at the second and final application of crizotinib group (P = 0.022). Baseline brain metastases were present in 25.5% (12/47) of patients in this study. 9 of the patients who developed disease progression during crizotinib treatment had new brain metastases or increased preexisting cranial foci. Most of them took the treatment strategy of continuing crizotinib or replacing the second/third generation ALK-TKI treatment combined with local radiotherapy for brain metastases.
The efficacy of crizotinib in patients with advanced NSCLC is related to the number of metastatic organs, age and timing of treatment. The use of crizotinib is prone to intracranial progression, and progression of simple brain metastases is not an indication that crizotinib is discontinued. Patients will continue to benefit from combination of local radiotherapy.
Deng H
，Li B
，Li L
，Peng J
，Lv T
，Liu Y
，Ding C
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