TY - JOUR
T1 - Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC
AU - Lucibello, Francesca
AU - Gounant, Valérie
AU - Aldea, Mihaela
AU - Duruisseaux, Michaël
AU - Perol, Maurice
AU - Chouaid, Christos
AU - Bennouna, Jaafar
AU - Fallet, Vincent
AU - Renault, Aldo
AU - Guisier, Florian
AU - Giroux-Leprieur, Etienne
AU - Wislez, Marie
AU - Toffart, Anne Claire
AU - Mazieres, Julien
AU - Basse, Clémence
AU - Hegarat, Nadia
AU - Carton, Matthieu
AU - Girard, Nicolas
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2025/1/1
Y1 - 2025/1/1
N2 - Introduction: Pralsetinib is a RET inhibitor found to have antitumor activity in advanced, metastatic, RET fusion-positive NSCLC. Objective: To assess real-world efficacy of pralsetinib and treatment sequences in patients with RET fusion-positive NSCLC. Design: Retrospective study of consecutive patients enrolled in the French expanded-access program for pralsetinib from December 1, 2019, to December 31, 2021. Participants: A total of 41 patients with advanced, refractory, RET fusion-positive NSCLC were included. Pralsetinib was administered at a daily dose of 400 mg based on safety and pharmacokinetic outcomes from previous phase 1/2 study. Results: Pralsetinib was administered as second line in 23 patients (56%) and as third line and beyond in 15 patients (37%). After a median follow-up of 26.3 months, pralsetinib was ongoing in 13 patients. Median real-world progression-free survival was 11.8 (95% confidence interval [CI]: 9.3–15.5) months. Objective response rate was 68% (95% CI: 50%–82%), and disease control rate was 89% (95% CI: 75%–97%). Subsequent line of systemic therapy was initiated in 11 patients. Median overall survival from pralsetinib initiation was 23.8 (95% CI: 16.5–not reached) months. Conclusion: In this extensive real-world cohort of patients with advanced or metastatic NSCLC harboring RET fusions, we highlight the antitumor efficacy of pralsetinib, particularly when administered in later treatment lines. We also observe the aggressive nature of disease progression, frequent utilization of chemotherapy and antiangiogenic agents as initial subsequent therapies, and limited insight into resistance mechanisms due to infrequent rebiopsy and genomic profiling at progression.
AB - Introduction: Pralsetinib is a RET inhibitor found to have antitumor activity in advanced, metastatic, RET fusion-positive NSCLC. Objective: To assess real-world efficacy of pralsetinib and treatment sequences in patients with RET fusion-positive NSCLC. Design: Retrospective study of consecutive patients enrolled in the French expanded-access program for pralsetinib from December 1, 2019, to December 31, 2021. Participants: A total of 41 patients with advanced, refractory, RET fusion-positive NSCLC were included. Pralsetinib was administered at a daily dose of 400 mg based on safety and pharmacokinetic outcomes from previous phase 1/2 study. Results: Pralsetinib was administered as second line in 23 patients (56%) and as third line and beyond in 15 patients (37%). After a median follow-up of 26.3 months, pralsetinib was ongoing in 13 patients. Median real-world progression-free survival was 11.8 (95% confidence interval [CI]: 9.3–15.5) months. Objective response rate was 68% (95% CI: 50%–82%), and disease control rate was 89% (95% CI: 75%–97%). Subsequent line of systemic therapy was initiated in 11 patients. Median overall survival from pralsetinib initiation was 23.8 (95% CI: 16.5–not reached) months. Conclusion: In this extensive real-world cohort of patients with advanced or metastatic NSCLC harboring RET fusions, we highlight the antitumor efficacy of pralsetinib, particularly when administered in later treatment lines. We also observe the aggressive nature of disease progression, frequent utilization of chemotherapy and antiangiogenic agents as initial subsequent therapies, and limited insight into resistance mechanisms due to infrequent rebiopsy and genomic profiling at progression.
KW - Lung Cancer
KW - Pralsetinib
KW - RET
KW - Second-Line
UR - http://www.scopus.com/inward/record.url?scp=85209085165&partnerID=8YFLogxK
U2 - 10.1016/j.jtocrr.2024.100743
DO - 10.1016/j.jtocrr.2024.100743
M3 - Article
AN - SCOPUS:85209085165
SN - 2666-3643
VL - 6
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
IS - 1
M1 - 100743
ER -