Targeted therapy in advanced NSCLC other than EGFR/ALK

Liam Chong Kin
University Malaya Medical Centre, Kuala Lumpur, Malaysia

Common EGFR gene sensitising mutations are found in non‐small cell lung cancer (NSCLC) of approximately 40% of patients, especially non-smokers, while less common oncogenic drivers are detected in another 20%-30% of NSCLC patients. Apart from KRAS mutations, rare oncogenic drivers are genetic alterations that occur in less than 5% of patients. These rare drivers include alterations in genes such as ROS1, RET, MET, BRAF, NTRK, HER2, NRG1 and EGFR exon 20 insertions. Targeted therapies have shown promising results in patients with NSCLC harbouring these less common oncogenic drivers, leading to significant tumour responses and improved outcomes compared to traditional chemotherapy. Comprehensive genomic profiling using next-generation sequencing is recommended to identify these less common drivers at the time of diagnosis. While targeted therapies have been successful, acquired resistance to these drugs remains a challenge, requiring ongoing research and development of new therapies including next-generation tyrosine kinase inhibitors, bispecific antibodies and antibody-drug conjugates.