Transcript
I'm David Carbone. I'm a thoracic medical oncologist and the Director of the Thoracic Oncology Center at Ohio State University in Columbus, Ohio. I would like to talk today a little bit about some of the recent progress in lung cancer.
A study that I thought was interesting and relevant to ALK was looking at baseline, clinical, and molecular features in ALTA-1L. This is a trial that was brigatinib versus crizotinib, but they looked at the different variants of the ALK fusion genes, and also, co-mutations with other things such as p53.
They showed that variant 3 appeared to be a poor prognostic biomarker in this study, and there was also a strong trend toward p53 mutations being associated with poor prognosis.
Many of the ALK tests (the ALK-IHC and the ALK-FISH) don't tell you which fusion variant you have, and many of the targeted panels that are in use now don't report p53.
These appear to be very significant modulators of outcome with ALK fusion–positive disease. If you have a p53 mutation, you have a hazard ratio of 1.7 higher risk of PFS progression. For variant 3, it's actually a 2.3-full higher risk of death compared to variant 1.
Those are the main things that caught my eye from ASCO this year relevant to ALK fusion-positive disease, but we still have a way to go with these patients.
Even though they have longer durations of survival, we're not curing these people. I think we need to look at combination therapies, at aggressive genetic monitoring of tumors as they go on through therapy to try to adapt to the acquired resistance profile that the patient's tumor has.
And we do need to look at better drugs for the CNS disease, so there's a lot of room for improvement still with ALK-targeting.
