Lung cancer : journal of the International Association for the Study of Lung Cancer
-
The incidence of CNS metastasis at the time of diagnosis of and during the natural disease history of advanced ROS1+ NSCLC is largely unknown. It is generally believed that the incidence of CNS metastasis is lower in ROS1+ NSCLC than ALK+ NSCLC as ROS1 fusions are regarded as a less powerful driver mutation than ALK fusions in ALK+ NSCLC based on the longer progression-free survival of ROS1+ NSCLC patients than ALK+ NSCLC patients treated with crizotinib. Here we reviewed the incidence of CNS metastasis from prospective clinical trials and retrospective case series from primarily single institution. ⋯ We reviewed reported intra-cranial activity of all preclinical and clinical development stage ROS1 TKIs and pemetrexed-based chemotherapy in ROS1+ NSCLC patients. While several ROS1 TKIs (i.e. entrectinib, cabozantinib, lorlatinib, repotrectinib) have reported intra-cranial response rates, there is no literature reporting on the intra-cranial activity of pemetrexed-based chemotherapy in ROS1+ NSCLC patients. 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.