Key clinical point: Lazertinib is well tolerated and active against advanced NSCLC harboring an EGFR mutation.
Major finding: The rate of grade 3 or 4 adverse events was 16%; the overall response rate and intracranial response rates were 54% and 44%, respectively.
Study details: A multicenter open-label phase 1/2 trial among 127 patients with EGFR mutation–positive advanced NSCLC who had experienced progression after a first- or second-generation EGFR TKI.
Disclosures: Dr. Cho disclosed relationships with numerous pharmaceutical companies, including Yuhan Corporation, which funded the trial.
Cho BC et al. Lancet Oncol. 2019 Oct 3. doi: 10.1016/S1470-2045(19)30504-2.
“[W]hy should anyone care about all these data for lazertinib?” Tejas Patil, MD, and D. Ross Camidge, MD, PhD, asked in a commentary, noting that another third-generation EGFR TKI, osimertinib (Tagrisso), has already received Food and Drug Administration approval for use in this setting and has generally similar activity and tolerability.
“Beyond any potential competitive price advantage that could be introduced after licensing, or idiosyncratic tolerance of one drug over another in individual patients, the real potential advantage of lazertinib might be hiding in plain sight. Specifically, lazertinib’s incompletely explored potential to treat CNS metastases,” they noted.
Although osimertinib appears to have good CNS activity, patients with CNS metastases continue to experience poorer progression-free survival. And even at higher doses causing greater toxicity, CNS penetration of that drug is limited.
“[T]he ideal drug for dedicated CNS dose regimen exploration is one in which the standard dosing has been set in the absence of substantial toxicity and in the absence of any plateauing of pharmacokinetic exposures,” Dr. Patil and Dr. Camidge maintained. And lazertinib appears to fit that bill.
The 44% intracranial response rate “is encouraging but still leaves a substantial amount of important data to be generated,” they contended. Although progression in the CNS was uncommon among patients without CNS metastases at baseline, the longer median progression-free survival at higher doses may indicate better CNS control and support further dose escalation.
“Lazertinib could be one of the pioneer drugs for redefining how we optimally address the CNS in oncology drug development,” they concluded. “Taking full advantage of the early drug-development process to explore the CNS potential of any oncology drug being considered in disease types with a high rate of CNS metastases should be part of a future that we can all look forward to.”
Dr. Patil is instructor of medicine, and Dr. Camidge is professor of medicine, in the division of medical oncology, department of medicine, at the University of Colorado, Anschutz Medical Campus, Aurora.