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Verfasst von:El Sayed, Mei [VerfasserIn]   i
 Bozorgmehr, Farastuk [VerfasserIn]   i
 Kazdal, Daniel [VerfasserIn]   i
 Volckmar, Anna-Lena [VerfasserIn]   i
 Sültmann, Holger [VerfasserIn]   i
 Fischer, Jürgen [VerfasserIn]   i
 Kriegsmann, Mark [VerfasserIn]   i
 Stenzinger, Albrecht [VerfasserIn]   i
 Thomas, Michael [VerfasserIn]   i
 Christopoulos, Petros [VerfasserIn]   i
Titel:Feasibility and challenges for sequential treatments in ALK-rearranged non-small-cell lung cancer
Verf.angabe:Mei Elsayed, Farastuk Bozorgmehr, Daniel Kazdal, Anna-Lena Volckmar, Holger Sültmann, Jürgen R. Fischer, Mark Kriegsmann, Albrecht Stenzinger, Michael Thomas and Petros Christopoulos
E-Jahr:2021
Jahr:20 April 2021
Umfang:8 S.
Teil:volume:11
 year:2021
 month:04
 elocationid:670483
 pages:1-8
 extent:8
Fussnoten:Gesehen am 29.04.2021
Titel Quelle:Enthalten in: Frontiers in oncology
Ort Quelle:Lausanne : Frontiers Media, 2011
Jahr Quelle:2021
Band/Heft Quelle:11(2021) vom: Apr., Artikel-ID 670483, Seite 1-8
ISSN Quelle:2234-943X
Abstract:Background: Anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK+ NSCLC) is a model disease for use of targeted therapies (TKI), which are administered sequentially to maximize patient survival. Methods: We retrospectively analyzed the flow of 145 consecutive TKI-treated ALK+ NSCLC patients across therapy lines. Suitable patients that could not receive an available next-line therapy ("attrition") were determined separately for various treatments, based on the approval status of the respective targeted drugs when each treatment failure occurred in each patient. Results: At the time of analysis, 70/144 (49%) evaluable patients were still alive. Attrition rates related to targeted treatments were approximately 25-30% and similar for administration of a second-generation (2G) ALK inhibitor (22%, 17/79) or any subsequent systemic therapy (27%, 27/96) after crizotinib, and for the administration of lorlatinib (27%, 6/22) or any subsequent systemic therapy (25%, 15/61) after any 2G TKI. The rate of chemotherapy implementation was 67% (62/93). Both administration of additional TKI (median overall survival [mOS] 59 vs. 41 months for multiple vs. one TKI lines, logrank p=0.002), and chemotherapy (mOS 41 vs. 16 months, logrank p<0.001) were significantly associated with longer survival. Main reason for patients foregoing any subsequent systemic treatment was rapid clinical deterioration (n=40/43 or 93%) caused by tumor progression. In 2/3 of cases (29/43), death occurred under the first failing therapy, while in 11/43 the treatment was switched, but the patient did not respond, deteriorated further, and died within 8 weeks. Conclusions: Despite absence of regulatory obstacles and no requirement for specific acquired mutations, 25-30% of ALK+ NSCLC patients forego subsequent systemic therapy due to rapid clinical deterioration, in several cases (approximately 1/3) associated with an ineffective first next-line choice. These results underline the need for closer patient monitoring and broader profiling in order to support earlier and better directed use of available therapies.
DOI:doi:10.3389/fonc.2021.670483
URL:Kostenfrei: Volltext ; Verlag: https://doi.org/10.3389/fonc.2021.670483
 Kostenfrei: Volltext: https://www.frontiersin.org/articles/10.3389/fonc.2021.670483/full
 DOI: https://doi.org/10.3389/fonc.2021.670483
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:ALK-rearranged non-small-cell lung cancer
 chemotherapy
 overall survival
 Sequential therapies
 tyrosine kinase inhibitors
K10plus-PPN:1756579016
Verknüpfungen:→ Zeitschrift
 
 
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