Ben Levy, MD, discusses the mechanism of resistance such as the G2032R solvent front mutation in patients who received crizotinib for lung cancer with ROS1 fusions and how to treat them.
Ben Levy, MD, clinical director of Medical Oncology at Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses the mechanism of resistance such as the G2032R solvent front mutation in patients who received crizotinib (Xalkori) for lung cancer with ROS1 fusions and how to treat them.
Levy says there are 2 drugs that target the G2032R mutation. One is lorlatinib (Lorbrena), which has already been approved for patients with ALK-positive lung cancer. It showed a 30% to 40% response rate in crizotinib-refractory patients with ROS1 and activity in the G2032R mutation.
The other drug is repotrectinib, which has not received any approvals yet. Levy explains that this agent is also specifically designed to overcome the G2032R mutation. Data from the 2019 American Society of Clinical Oncology Annual Meeting showed meaningful responses of about 40% in patients who were refractory to crizotinib as well as responses in the brain.
It important that contemporary diagnostics platforms such as an RNA and DNA next-generation sequencing platform are deployed in this setting to interrogate ROS1 in patients, according to Levy. For patients with ROS1-rearranged lung cancer, crizotinib and entrectinib (Rozlytrek) are approved treatments and have shown response rates of over 70% with a progression-free survival of about 19 months in competitive outcomes. Entrectinib also showed an intracranial response.