TY - JOUR
T1 - Pan-cancer efficacy of pralsetinib in patients with RET fusion–positive solid tumors from the phase 1/2 ARROW trial
AU - Subbiah, Vivek
AU - Cassier, Philippe A.
AU - Siena, Salvatore
AU - Garralda, Elena
AU - Paz-Ares, Luis
AU - Garrido, Pilar
AU - Nadal, Ernest
AU - Vuky, Jacqueline
AU - Lopes, Gilberto
AU - Kalemkerian, Gregory P.
AU - Bowles, Daniel W.
AU - Seetharam, Mahesh
AU - Chang, Jianhua
AU - Zhang, Hui
AU - Green, Jennifer
AU - Zalutskaya, Alena
AU - Schuler, Martin
AU - Fan, Yun
AU - Curigliano, Giuseppe
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/8
Y1 - 2022/8
N2 - Oncogenic RET fusions 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 RET fusion–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 RET fusion 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 RET fusion 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 RET fusion–positive solid tumors.
AB - Oncogenic RET fusions 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 RET fusion–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 RET fusion 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 RET fusion 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 RET fusion–positive solid tumors.
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U2 - 10.1038/s41591-022-01931-y
DO - 10.1038/s41591-022-01931-y
M3 - Article
C2 - 35962206
AN - SCOPUS:85135806891
SN - 1078-8956
VL - 28
SP - 1640
EP - 1645
JO - Nature medicine
JF - Nature medicine
IS - 8
ER -