ROS1-Rearranged NSCLC
Chromosomal rearrangements of the gene encoding ROS1 have been found in
approximately 1% of patients with NSCLC [63]. Due to considerable
homology between the kinase domains of ROS1 and ALK, drugs used to treat
ALK-positive tumors including crizotinib[63], ceritinib [64] and
lorlatinib [65] have also shown marked activity in ROS1-positive
tumors. Crizotinib was found to have a response rate of 72% and median
PFS of 19 months in 50 patients with NSCLC and ROS1 rearrangement
[63]. Repotrectinib (TPX-0005) may be an effective therapeutic
option for patients with NTRK1–3, ROS1 or ALK-rearranged advanced NSCLC
who have progressed on earlier-generation TKIs as it is known to
overcome resistance due to acquired mutations involving NTRK 1-3, ROS1
and ALK [66].Cabozantinib has also demonstrated anti-ROS1 activity
in the second-line setting, including activity against G2032R.Most
agents demonstrated good tolerability, with safety and efficacy data
that are being confirmed in ongoing clinical trials, except cabozantinib
which isassociated with higher toxicity, and it is therefore limited as
a therapeutic agent for some patients.