Dr. Drilon on Targeted Therapies for Patients With ROS1-Rearranged Lung Cancer

Alexander Drilon, MD
Published: Wednesday, Apr 18, 2018



Alexander Drilon, MD, clinical director, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, discusses targeted agents for patients with ROS1-rearranged lung cancer.

ROS1 rearrangements are found in about 1% to 2% of patients with non–small cell lung cancer (NSCLC). That’s about half the prevalence of ALK-rearranged lung cancers. Like ALK rearrangements, these are strong drivers of cancer growth. Targeted therapies can be very effective in treating these patient subsets. The current FDA-approved therapy for ROS1-rearranged lung cancer is crizotinib (Xalkori). The tyrosine kinase inhibitor achieves response rates in excess of 60% and a median progression-free survival of about 19 months. That quite exceeds what physicians expect to see in ALK-rearranged lung cancers, says Drilon.

Other agents like ceritinib (Zykadia) are being explored for ROS1 rearrangements. The results of the phase II trial were presented and showed a similar response rate greater than 60%. However, ceritinib is generally less tolerable at the full dose as compared with crizotinib. Entrectinib and lorlatinib are also being explored in these subtypes. Cabozantinib (Cabometyx), brigatinib (Alunbrig), and other investigational agents have been shown to have ROS1 activity as well.
 


Alexander Drilon, MD, clinical director, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, discusses targeted agents for patients with ROS1-rearranged lung cancer.

ROS1 rearrangements are found in about 1% to 2% of patients with non–small cell lung cancer (NSCLC). That’s about half the prevalence of ALK-rearranged lung cancers. Like ALK rearrangements, these are strong drivers of cancer growth. Targeted therapies can be very effective in treating these patient subsets. The current FDA-approved therapy for ROS1-rearranged lung cancer is crizotinib (Xalkori). The tyrosine kinase inhibitor achieves response rates in excess of 60% and a median progression-free survival of about 19 months. That quite exceeds what physicians expect to see in ALK-rearranged lung cancers, says Drilon.

Other agents like ceritinib (Zykadia) are being explored for ROS1 rearrangements. The results of the phase II trial were presented and showed a similar response rate greater than 60%. However, ceritinib is generally less tolerable at the full dose as compared with crizotinib. Entrectinib and lorlatinib are also being explored in these subtypes. Cabozantinib (Cabometyx), brigatinib (Alunbrig), and other investigational agents have been shown to have ROS1 activity as well.
 



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