Crizotinib, as an ALK inhibitor, has been used in the treatment of ALK-rearranged NSCLC for several years and some adverse effects should be given attention.
Patients with an EGFR or ALK alteration show a better clinical outcome with tyrosine kinase inhibitor (TKI) treatment compared to chemotherapy.Patients with a ROS1 rearrangement or a BRAF V600E mutation show favorable clinical outcome with TKI treatment compared to chemotherapy, although randomized trials are not available.Patients on TKIs will eventually develop disease progression because of acquired resistance.The treatment with immunotherapy in EGFR and ALK-positive NSCLC patients did not improve overall survival over that of chemotherapy.Blood-based genetic analysis provides the opportunity to noninvasively screen patients for the presence of oncogenic drivers and to monitor resistance during TKI treatment.
In this article, we review recent data on the use of epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors for treatment of patients with NSCLC and BM.
Patients with advanced NSCLC with ALK or ROS1 rearrangements who initiated lorlatinib therapy between November 2016 and July 2018 were retrospectively analyzed.
Low-expressed lincROR was related to a favorable prognosis of patients with EML-ALKNSCLC. lincROR overexpression could enhance the stemness features of EML-ALK<sup>+</sup> NSCLC cells which were repressed by ALK knockdown.
Two anaplastic lymphoma kinase-rearranged non-small-cell lung cancer patients (one with pre-existing renal impairment) were identified during periods of time on and off crizotinib.
This review summarizes the existing clinical data and ongoing research pertaining to the clinical application of ALK inhibitors in patients with non-small cell lung cancer.
Although the adnexal location is an uncommon metastasis site from lung cancer, oncologists should be aware of the possibility of such metastasis for female patients with ALK rearrangement NSCLC.
This case of a patient with EML4-ALK-rearranged non-small-cell lung cancer shows that sequential treatment with next-generation ALK tyrosine kinase inhibitors, including rechallenge, can induce profound remission even in heavily pretreated patients, especially if the central nervous system is the site of progression.
The incidence of ALK rearrangements was investigated in 763 NSCLC specimens by immunohistochemistry using a D5F3 antibody, and EGFR mutations were assessed by amplification refractory mutation system (ARMS) in 222 patients with lung adenocarcinoma.
EML4-ALK fusion genes define a molecular subset of NSCLC with distinct clinical characteristic (lung adenocarcinoma, never or former smoker, usually mutually exclusive with EGFR mutations).
However, recent evidence that aberrant ALK activity is also involved in an expanding number of tumor types, such as other lymphomas, inflammatory myofibroblastic tumor, neuroblastomas and some carcinomas, including non-small cell lung carcinomas, is boosting research progress in ALK-targeted therapies.
This kit was used in 1 of the 2 pivotal trials leading to the FDA approval of crizotinib and has become the gold standard for detecting ALK rearrangement in NSCLC.
Ceritinib demonstrated a statistically significant effect on the progression-free survival versus chemotherapy in patients with advanced anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) as the first therapy or after previous treatment with crizotinib and one or two prior chemotherapy regimens in global phase 3 studies.
The guideline summarizes the importance of targetable mutations in NSCLC such as epidermal growth factor receptor (EGFR), rearrangements in anaplastic lymphoma kinase and receptor tyrosine kinase encoded by ROS-1 gene, overexpression of programmed cell death ligand-1 and resistant EGFR mutations.
The clinical efficacy of the ALK inhibitor crizotinib has been demonstrated in ALK fusion-positive NSCLC; however, resistance to crizotinib certainly occurs through ALK secondary mutations in clinical use.
Clinical Utility of Cell-Free DNA for the Detection of <i>ALK</i> Fusions and Genomic Mechanisms of ALK Inhibitor Resistance in Non-Small Cell Lung Cancer.