OncLive® On Air S14 Ep19: Zidesamtinib Is Associated With CNS Activity and Low Rates of Neurologic AEs in Pretreated ROS1+ NSCLC: With Alexander Drilon, MD
Sep 18, 2025
In this discussion, Dr. Alexander Drilon, a lung cancer expert from Memorial Sloan Kettering Cancer Center, dives into the ARROS-1 trial of zidesamtinib for ROS1-positive non-small cell lung cancer. He highlights the promising efficacy data, noting the drug's high central nervous system response rates and low neurological side effects. Dr. Drilon explores zidesamtinib's unique mechanism and its potential to redefine first-line treatment, especially for patients resistant to prior TKI therapies. His insights underscore zidesamtinib’s promising role in advancing lung cancer therapy.
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Activity After Prior Next-Gen TKIs
- Alexander Drilon described patients who progressed after repotrectinib or talotrectinib yet responded to zidesamtinib in ARROS-1.
- He emphasized this is the first drug to show activity in that post-repotrectinib/talotrectinib setting, offering hope for those patients.
Marked Improvement In Durability
- Drilon noted cross-trial comparisons suggest zidesamtinib yields higher response rates and greater durability than repotrectinib/talotrectinib.
- He highlighted median PFS rising from ~9 months with older agents to 23.8 months with zidesamtinib in one-prior-TKI patients.
TRK-Sparing Design Lowers Neurologic AEs
- Zidesamtinib was designed to spare TRK inhibition to avoid neurologic side effects seen with earlier TKIs.
- Drilon reported common AEs were mostly grade 1–2 like peripheral edema and CPK increase, without the TRK-related neurologic symptoms.