| Autor: |
Subbiah, Vivek, Cassier, Philippe A., Siena, Salvatore, Garralda, Elena, Paz-Ares, Luis, Garrido, Pilar, Nadal, Ernest, Vuky, Jacqueline, Lopes, Gilberto, Kalemkerian, Gregory P., Bowles, Daniel W., Seetharam, Mahesh, Chang, Jianhua, Zhang, Hui, Green, Jennifer, Zalutskaya, Alena, Schuler, Martin, Fan, Yun, Curigliano, Giuseppe |
| Zdroj: |
Nature Medicine; 20220101, Issue: Preprints p1-6, 6p |
| Abstrakt: |
Oncogenic RETfusions occur in diverse cancers. Pralsetinib is a potent, selective inhibitor of RET receptor tyrosine kinase. ARROW (NCT03037385, ongoing) was designed to evaluate pralsetinib efficacy and safety in patients with advanced RET-altered solid tumors. Twenty-nine patients with 12 different RETfusion–positive solid tumor types, excluding non-small-cell lung cancer and thyroid cancer, who had previously received or were not candidates for standard therapies, were enrolled. The most common RETfusion partners in 23 efficacy-evaluable patients were CCDC6(26%), KIF5B(26%) and NCOA4(13%). Overall response rate, the primary endpoint, was 57% (95% confidence interval, 35–77) among these patients. Responses were observed regardless of tumor type or RETfusion partner. Median duration of response, progression-free survival and overall survival were 12 months, 7 months and 14 months, respectively. The most common grade ≥3 treatment-related adverse events were neutropenia (31%) and anemia (14%). These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition, indicating pralsetinib’s potential as a well-tolerated treatment option with rapid, robust and durable anti-tumor activity in patients with diverse RETfusion–positive solid tumors. |
| Databáze: |
Supplemental Index |
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