Addressing Fusions in NSCLC
RET fusion is a predictive biomarker used in cabozantinib and vandetanib for patients with NSCLC.
Based on the presence of RET fusion, there are currently 2 NCCN guidelines that support its use as a targeted biomarker-directed therapy, with NSCLC and thyroid gland medullary carcinoma having the most therapies targeted against RET fusion.
The NTRK1 gene plays a role in developing and maintaining the nervous system. It is also a predictive biomarker used in larotrectinib. Gene fusions of NTRK can lead to the development of abnormal proteins that may cause cancer cell growth.
Mutations to this gene have been found in patients with lung adenocarcinoma, colorectal cancer, papillary thyroid cancer, glioblastoma multiforme and in cholangiocarcinoma. Malignant tumors have the most therapies targeted against NTRK1 fusion.
ALK rearrangements have been identified in colon, ovarian and non-small cell lung cancers where ALK fusions comprise approximately RET STK11 3-5% of lung tumors.
Although ALK fusion products have been shown to confer sensitivity to ALK tyrosine kinase inhibitors, emergence of mutations in the ALK kinase domain have been reported to confer resistance to treatment.
ROS1 gene rearrangement fusion events haVve been identified in approximately 2% of lung cancer cases, and have been detected in other cancers including ovarian carcinoma, sarcoma and cholangiocarcinomas.
Harboring a ROS1 mutation may confer increased sensitivity to ROS1 inhibitors.
Somatic mutations have also been identified that may drive resistance or sensitivity to ROS1 inhibitors.
In the US, InVisionFirst®-Lung is now covered for Medicare and United Health Care (UHC) patients with advanced (Stage IIIB/IV) NSCLC. See full details here.