In summary, better understanding the high incidence of CNS metastasis in ROS1+ NSCLC patients, how certain ROS1 fusion variant may increase the incidence of CNS metastasis, and any intra-cranial efficacy data of pemetrexed in ROS1+ NSCLC are all urgently needed.
TMEM106B-ROS1 is a novel ROS1 fusion variant in NSCLC identified by comprehensive genomic profiling and should be included in any ROS1 detecting assay that depends on identifying the corresponding fusion partners such as reverse transcriptase-polymerase chain reaction (RT-PCR).
ALK, ROS1, and MET are targeted by Crizotinib, a tyrosine kinase inhibitor which has been approved for treatment of ALK-rearranged non-small-cell lung cancer.
We retrospectively identified patients with NSCLC who were screened for ROS1 fusion using multiplex reverse transcription-polymerase chain reaction (RT-PCR) from October 2013 to February 2016.
Here, we present updated antitumor activity, overall survival (OS) and safety data (additional 46.2 months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001.
There are conflicting data on the incidence of CNS metastases in stage IV ROS1-positive NSCLC and the rate of CNS progression during crizotinib therapy.
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC).
Chromosomal rearrangements of ALK and ROS1 genes in non-small cell lung carcinoma (NSCLC) define a molecular subgroup of lung adenocarcinoma (ADC) that is amenable to targeted therapy with tyrosine kinase inhibitors (TKIs) crizotinib.
Among patients with NSCLC who received pemetrexed for an extended time, those with ALK and ROS1 gene rearrangements were proportionally overrepresented compared with that anticipated in a general nonsquamous NSCLC population, and patients with oncogenic driver mutations had improved outcomes.
These results demonstrated how the mutated residues tune the crizotinib response and may assist kinase inhibitor development especially for ALK G1202R, analogous to the ROS1G2302R and MET G1163R mutations that are also resistant to crizotinib treatment in NSCLC.
Crizotinib is a standard treatment for advanced anaplastic lymphoma kinase (ALK)- or ROS1-fusion-gene-positive non-small cell lung cancer; however, serious adverse events (AEs), including elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and interstitial lung disease (ILD), develop occasionally.
<i>ROS1</i> rearrangements define a distinct molecular subset of non-small-cell lung cancer (NSCLC), which can be treated effectively with crizotinib, a tyrosine kinase inhibitor (TKI) targeting <i>ROS1/MET/ALK</i> rearrangements.
Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients.
We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia).
We review the tissue requirements for ROS1 testing by immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) and we present a testing algorithm for advanced NSCLC and consider how the future of pathology testing for ROS1 may evolve.
Entrectinib is also under regulatory review in the USA (PDUFA date 18 August 2019) and EU [Priority Medicines (PRIME) designation] for NTRK-positive solid tumours and ROS1-positive NSCLC.
To evaluate the frequency and clinicopathological features of ROS1 and RET rearrangements in N2 node positive stage IIIA (IIIA-N2) non-small cell lung cancer (NSCLC) patients, we retrospectively screened 204 cases with a tissue microarray (TMA) panel by fluorescent in situ hybridization (FISH), and confirmed by direct sequencing and immunohistochemistry (IHC).
In this review, we discuss ROS1 rearrangements in non-small cell lung cancer, and provide an update on targeting ROS1-rearranged non-small cell lung cancer with crizotinib and newer generation tyrosine kinase inhibitors.