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Selpercatinib Controls Central Nervous System Disease in Patients With NSCLC With RET Fusion - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/37087123/
Selpercatinib Controls Central Nervous System Disease in Patients With NSCLC With RET Fusion
Relevance: In clinical aspects, early initiation of selpercatinib is associated with decreased rates of CNS metastasis formation and progression; therefore, selpercatinib may play a preventive role.
• Source: Journal of Thoracic Oncology
• Conclusions/Relevance: “With this report by Murciano-Goroff et al., selpercatinib has likely joined osimertinib and lorlatinib as agents with activity in the CNS for their respective mutant NSCLC subtypes. We look forward to identifying drugs to join the list of CNS active agents for ROS1+ and HER2 exon20 insertion positive NSCLC.”
• The authors of the editorial cited the LIBRETTO-001 and ARROW studies.
• “The incidences of central nervous system (CNS) metastasis among newly diagnosed treatment-naive patients with RET-positive (+) NSCLC enrolled into the registrational selpercatinib trial (LiBRETTO-001) and in the pivotal phase 2 pralsetinib trial (ARROW) were 23.6% (n = 16 of 69)1 and 33% (n = 25 of 75), respectively. Both approved RET-specific tyrosine kinase inhibitors (TKIs), selpercatinib and pralsetinib, achieved high intracranial overall response rate of 85% (95% confidence interval [CI]: 65–96) (n = 22 of 26)1 and 70% (95% CI: 35–93) (n = 7 of 10), respectively,” they wrote.
• The duration of response in selpercatinib-treated patients with measurable CNS metastasis was 9.4 months. In 69 selpercatinib-treated previously treatment-naïve patients without baseline CNS metastasis, the overall median PFS was 22.0 months.
• For pralsetinib-treated patients, the median CNS duration of response was 10.5 months. The overall median PFS was 13.0 months in 75 patients with pralsetinib-treated previously treatment-naive RET+ NSCLC.
• The authors of the editorial noted that approximately 70% of newly diagnosed patients with treatment-naive advanced RET+ NSCLC exhibited no CNS metastasis at diagnosis.
• Drilon and colleagues found in their retrospective analysis of cumulative incidence rate (CIR) of CNS metastasis in the three major RTK fusion+ NSCLC (ALK, ROS1, RET) that although ALK+ NSCLC has the highest and most unrelenting CIR in patients with CNS metastasis, RET+ NSCLC without baseline CNS metastasis comes in at second. In the latter group, the CIR is close to 40% at 4 years, with a lifetime CIR of 46% in all patients with stage IV RET+ NSCLC.