> Details
Griesinger, Frank
[Author];
Curigliano, G.
[Author];
Thomas, Michael
[Author];
Subbiah, V.
[Author];
Baik, C. S.
[Author];
Tan, D. S. W.
[Author];
Lee, D. H.
[Author];
Misch, D.
[Author];
Garralda, E.
[Author];
Kim, D. -W
[Author];
van der Wekken, A. J.
[Author];
Gainor, J. F.
[Author];
Paz-Ares, L.
[Author];
Liu, S. V.
[Author];
Kalemkerian, G. P.
[Author];
Houvras, Y.
[Author];
Bowles, D. W.
[Author];
Mansfield, A. S.
[Author];
Lin, J. J.
[Author];
Smoljanovic, V.
[Author];
Rahman, A.
[Author];
Kong, S.
[Author];
Zalutskaya, A.
[Author];
Louie-Gao, M.
[Author];
[...]
Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy
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- Media type: E-Article
- Title: Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy : update from the ARROW trial
- Contributor: Griesinger, Frank [VerfasserIn]; Curigliano, G. [VerfasserIn]; Thomas, Michael [VerfasserIn]; Subbiah, V. [VerfasserIn]; Baik, C. S. [VerfasserIn]; Tan, D. S. W. [VerfasserIn]; Lee, D. H. [VerfasserIn]; Misch, D. [VerfasserIn]; Garralda, E. [VerfasserIn]; Kim, D. -W. [VerfasserIn]; van der Wekken, A. J. [VerfasserIn]; Gainor, J. F. [VerfasserIn]; Paz-Ares, L. [VerfasserIn]; Liu, S. V. [VerfasserIn]; Kalemkerian, G. P. [VerfasserIn]; Houvras, Y. [VerfasserIn]; Bowles, D. W. [VerfasserIn]; Mansfield, A. S. [VerfasserIn]; Lin, J. J. [VerfasserIn]; Smoljanovic, V. [VerfasserIn]; Rahman, A. [VerfasserIn]; Kong, S. [VerfasserIn]; Zalutskaya, A. [VerfasserIn]; Louie-Gao, M. [VerfasserIn]; Boral, A. L. [VerfasserIn]; Mazières, J. [VerfasserIn]
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imprint:
13 August 2022
- Published in: Annals of oncology ; 33(2022), 11 vom: Nov., Seite 1168-1178
- Language: English
- DOI: 10.1016/j.annonc.2022.08.002
- ISSN: 1569-8041
- Identifier:
- Keywords: frontline therapy ; non-small-cell lung cancer ; pralsetinib ; RET fusion ; RET inhibition ; targeted therapy
- Origination:
- Footnote:
- Description: Background - RET fusions are present in 1%-2% of non-small-cell lung cancer (NSCLC). Pralsetinib, a highly potent, oral, central nervous system-penetrant, selective RET inhibitor, previously demonstrated clinical activity in patients with RET fusion-positive NSCLC in the phase I/II ARROW study, including among treatment-naive patients. We report an updated analysis from the ARROW study. - Patients and methods - ARROW is a multi-cohort, open-label, phase I/II study. Eligible patients were ≥18 years of age with locally advanced or metastatic solid tumours and an Eastern Cooperative Oncology Group performance status of 0-2 (later 0-1). Patients initiated pralsetinib at the recommended phase II dose of 400 mg once daily until disease progression, intolerance, consent withdrawal, or investigator’s decision. The co-primary endpoints (phase II) were overall response rate (ORR) by blinded independent central review and safety. - Results - Between 17 March 2017 and 6 November 2020 (data cut-off), 281 patients with RET fusion-positive NSCLC were enrolled. The ORR was 72% [54/75; 95% confidence interval (CI) 60% to 82%] for treatment-naive patients and 59% (80/136; 95% CI 50% to 67%) for patients with prior platinum-based chemotherapy (enrolment cut-off for efficacy analysis: 22 May 2020); median duration of response was not reached for treatment-naive patients and 22.3 months for prior platinum-based chemotherapy patients. Tumour shrinkage was observed in all treatment-naive patients and in 97% of patients with prior platinum-based chemotherapy; median progression-free survival was 13.0 and 16.5 months, respectively. In patients with measurable intracranial metastases, the intracranial response rate was 70% (7/10; 95% CI 35% to 93%); all had received prior systemic treatment. In treatment-naive patients with RET fusion-positive NSCLC who initiated pralsetinib by the data cut-off (n = 116), the most common grade 3-4 treatment-related adverse events (TRAEs) were neutropenia (18%), hypertension (10%), increased blood creatine phosphokinase (9%), and lymphopenia (9%). Overall, 7% (20/281) discontinued due to TRAEs. - Conclusions - Pralsetinib treatment produced robust efficacy and was generally well tolerated in treatment-naive patients with advanced RET fusion-positive NSCLC. Results from the confirmatory phase III AcceleRET Lung study (NCT04222972) of pralsetinib versus standard of care in the first-line setting are pending.
- Access State: Open Access