Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC
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 pat...
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Elsevier
2025-01-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001139 |
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| author | Francesca Lucibello, MD Valérie Gounant, MD, PhD Mihaela Aldea, MD, PhD Michaël Duruisseaux, MD, PhD Maurice Perol, MD Christos Chouaid, MD Jaafar Bennouna, MD, PhD Vincent Fallet, MD Aldo Renault, MD Florian Guisier, MD, PhD Etienne Giroux-Leprieur, MD, PhD Marie Wislez, MD, PhD Anne-Claire Toffart, MD, PhD Julien Mazieres, MD, PhD Clémence Basse, MD, PhD Nadia Hegarat, PhD Matthieu Carton, MD Nicolas Girard, MD, PhD |
| author_facet | Francesca Lucibello, MD Valérie Gounant, MD, PhD Mihaela Aldea, MD, PhD Michaël Duruisseaux, MD, PhD Maurice Perol, MD Christos Chouaid, MD Jaafar Bennouna, MD, PhD Vincent Fallet, MD Aldo Renault, MD Florian Guisier, MD, PhD Etienne Giroux-Leprieur, MD, PhD Marie Wislez, MD, PhD Anne-Claire Toffart, MD, PhD Julien Mazieres, MD, PhD Clémence Basse, MD, PhD Nadia Hegarat, PhD Matthieu Carton, MD Nicolas Girard, MD, PhD |
| author_sort | Francesca Lucibello, MD |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0c41f917b5ca448d96c9f58872859bd4 |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj-art-0c41f917b5ca448d96c9f58872859bd42025-01-20T04:17:52ZengElsevierJTO Clinical and Research Reports2666-36432025-01-0161100743Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLCFrancesca Lucibello, MD0Valérie Gounant, MD, PhD1Mihaela Aldea, MD, PhD2Michaël Duruisseaux, MD, PhD3Maurice Perol, MD4Christos Chouaid, MD5Jaafar Bennouna, MD, PhD6Vincent Fallet, MD7Aldo Renault, MD8Florian Guisier, MD, PhD9Etienne Giroux-Leprieur, MD, PhD10Marie Wislez, MD, PhD11Anne-Claire Toffart, MD, PhD12Julien Mazieres, MD, PhD13Clémence Basse, MD, PhD14Nadia Hegarat, PhD15Matthieu Carton, MD16Nicolas Girard, MD, PhD17Institut Curie, Institut du Thorax, Paris, FranceUniversité Paris Cité, Service d’Oncologie thoracique & CIC1425 INSERM, Hôpital Bichat Claude Bernard, AP-HP. Nord, Paris, FranceGustave Roussy, Oncologie médicale, Villejuif, FranceHospices Civils de Lyon, Hôpital Louis Pradel, Bron, FranceCentre Léon Bérard, Lyon, FranceCHIC, Service de Pneumologie, Créteil, FranceHôpital Foch, Oncologie Médicale, Suresnes, FranceAPHP, Service de Pneumologie, Hôpital Tenon, Paris, FranceCH, Service de Pneumologie, Pau, FranceNormandie Univ, UNIROUEN, LITIS Lab QuantIF team EA4108, CHU Rouen, and Inserm CIC-CRB 1404, Rouen, FranceAPHP, Service de Pneumologie, Hôpital Ambroise Paré, Boulogne, FranceAPHP, Service de Pneumologie, Hôpital Cochin, Paris, FranceCHUGA, Service de Pneumologie, Grenoble, FranceCHU Toulouse, Service de Pneumologie, Toulouse, FranceInstitut Curie, Institut du Thorax, Paris, France; Paris Saclay, UVSQ, UFR Simone Veil, Versailles, FranceInstitut Curie, Institut du Thorax, Paris, FranceInstitut Curie, Institut du Thorax, Paris, FranceInstitut Curie, Institut du Thorax, Paris, France; Paris Saclay, UVSQ, UFR Simone Veil, Versailles, France; Corresponding author. Address for correspondence: Nicolas Girard, MD, PhD, Institut Curie, 26 rue d’Ulm, 75005 Paris, France.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.http://www.sciencedirect.com/science/article/pii/S2666364324001139PralsetinibLung CancerRETSecond-Line |
| spellingShingle | Francesca Lucibello, MD Valérie Gounant, MD, PhD Mihaela Aldea, MD, PhD Michaël Duruisseaux, MD, PhD Maurice Perol, MD Christos Chouaid, MD Jaafar Bennouna, MD, PhD Vincent Fallet, MD Aldo Renault, MD Florian Guisier, MD, PhD Etienne Giroux-Leprieur, MD, PhD Marie Wislez, MD, PhD Anne-Claire Toffart, MD, PhD Julien Mazieres, MD, PhD Clémence Basse, MD, PhD Nadia Hegarat, PhD Matthieu Carton, MD Nicolas Girard, MD, PhD Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC JTO Clinical and Research Reports Pralsetinib Lung Cancer RET Second-Line |
| title | Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC |
| title_full | Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC |
| title_fullStr | Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC |
| title_full_unstemmed | Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC |
| title_short | Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC |
| title_sort | real world outcomes of pralsetinib in ret fusion positive nsclc |
| topic | Pralsetinib Lung Cancer RET Second-Line |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001139 |
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