Conclusions
•
ROS1 fusions define a rare (1-2%) subgroup of lung adenocarcinoma
enriched in never-smokers and are prognostically favourable.
•
Crizotinib is highly active, well tolerated and the approved 1L treatment.
•
Resistance mechanisms include mutations in the kinase domain and
activation of bypass pathways.
•
Several drugs overcome crizotinib-resistance in vitro and in patients
(e.g. lorlatinib, cabozantinib, entrectinib).
•
Molecular and functional analyses of rebiopsies are essential to develop
rational strategies for molecularly-guided sequential therapy.
