Although non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK),
ROS Proto-Oncogene 1 (ROS1), and rearranged during transfection (RET) gene fusions initially
respond well to tyrosine kinase inhibitor (TKI) therapies, acquired resistance is inevitable.
In many of these cases, increased activation of the (epidermal growth factor receptor (ERBB)
or mesenchymal-epithelial transition (cMet) pathways appears to be a bypass signaling
mechanism that allows these cancer cells to circumvent the selective pressure from TKIs.
Recent data have suggested that these pathways compensate for each other in situations where
one pathway is inhibited, leading to "kinase switch" drug resistance. Thus, the expected
inhibition of both pathways via treatment with the amivantamab and combination TKI
combination may improve overall efficacy by limiting the compensatory pathway activation.