Oncodrivers in Advanced or Metastatic NSCLC: Current and Future Standards of Care - Episode 10
Real-World (RW) Outcomes and Novel Strategies in ROS1-Positive NSCLC
Panelists discuss how real-world data becomes crucial for guiding treatment decisions in rare subsets like ROS1-positive patients where head-to-head trials are challenging, and how next-generation inhibitors like NVL-520 and taletrectinib aim to improve efficacy while reducing TRK-related toxicities through more selective targeting.
Future ROS1 Inhibitor Development
Next-generation ROS1 inhibitors aim to improve upon current agents by addressing specific limitations. NVL-520 represents a promising ROS1-selective inhibitor designed to spare TRK activity, potentially reducing neurocognitive toxicity while maintaining CNS penetration and activity against resistance mutations. Early data shows compelling activity in acquired resistance settings, with higher response rates in post-crizotinib patients and continued activity after later-generation ROS1 inhibitors.
Taletrectinib offers another approach as a ROS1/TRK inhibitor that relatively spares TRK-B, potentially reducing neurocognitive adverse effects. The pooled TRUST-1 and TRUST-2 analysis demonstrated progression-free survival approaching 4 years, representing extraordinary efficacy in the ROS1 space. However, this international data requires validation in broader patient populations before definitive conclusions about superiority can be drawn.
The challenge of advancing superior agents to first-line therapy parallels issues seen in ALK development, where exceptional current standards make randomized trials with extended follow-up periods necessary. Real-world data and novel trial designs may accelerate development timelines for patients who cannot wait years for optimal treatment determination. The goal remains identifying agents that match or exceed repotrectinib's efficacy while providing improved tolerability profiles.
Related Content:
