Dana-Farber Cancer Institute's Dr. Julia Rotow reported on a study looking at silevertinib, with data showing it may offer a new first-line option for hard-to-treat EGFR non-small cell lung cancer variants, with encouraging brain activity and manageable side effects.
Patients with non-classical EGFR mutations face worse outcomes on standard available 3rd-generation EGFRRTKIs and were excluded from many of the current first line combination studies which showed such benefits for patients with classically mutated disease. Uh, for a subset of these are non-classical mutations, the 2nd generation, uh, EGFRTKIfatinib is indeed FDA approved. This agent carries more limited CNS activity and a difficult toxicity profile than our later 3rd-generation EGFFR inhibitors. Uh, silvertinib is an investigational EGFR inhibitor which is intended to more potently target these uncommon mutations, and not for improved seS activity, hopefully to address some of these challenges and improve outcomes for this patient population. The ESA is pleased to present on behalf of the study team, the efficacy outcomes from cohort 3 of the study, again looking at patients with treatment naive, non-classical EGFR mutant non-small cell lung cancer. Uh, overall, Acelavertinib produced a 60% response rate for these patients, 56% in PAC mutations, um, which we know are the more challenging subset to address with currently available third-generation EGFRTTIs and produced the median progression-free survival of 152.2 months, which compared favorably to some of the numbers reported, um, in historical controls, particularly for those with PAC mutation-positive disease. Of note among patients with measurable untreated CNS disease, the CNS intracranial response rate was 86%, showing significant potential for CNS activity, and this, of course, is such a clinical challenge for our patients with EGFR m and lung cancer. This is really critical feature, I think for any agent we're thinking about, about uh designing or developing in this space. Uh, the safety profile for this agent was, uh, generally as expected. It's an EGFR inhibitor. We did indeed see a classical wild type EGFR related toxicities, so most commonly rash, diarrhea, pericular stomatitis. These did occur in the majority of patients and did result in dose reductions. So the dose reduction rate was 84% among patients on study. However, the rate of treatment discontinuation for adverse events is only 14%. So most patients with dose reduction were able to stay on therapy, um, successfully. And also quite importantly, The average time point to uh Nadder of disease control occurred after dose reduction. So these patients who are having to go down on dose for toxicities were still deriving benefit and that was measured both systemically and at CNS nadders. So again, we looked like at the lower dose, still seeing activity across the blood-brain barrier. Uh, so in summary, uh, so Overtinib showed encouraging activity in this very challenging to treat subgroup of non-small cell lung cancer, and we look forward to future randomized studies further investigating this in this space.
