Feasibility and challenges for sequential treatments in ALK-rearranged non-small-cell lung cancer

• Verfasst von: El Sayed, Mei [VerfasserIn]
• Verfasst von: Bozorgmehr, Farastuk [VerfasserIn]
• Verfasst von: Kazdal, Daniel [VerfasserIn]
• Verfasst von: Volckmar, Anna-Lena [VerfasserIn]
• Verfasst von: Sültmann, Holger [VerfasserIn]
• Verfasst von: Fischer, Jürgen [VerfasserIn]
• Verfasst von: Kriegsmann, Mark [VerfasserIn]
• Verfasst von: Stenzinger, Albrecht [VerfasserIn]
• Verfasst von: Thomas, Michael [VerfasserIn]
• Verfasst von: Christopoulos, Petros [VerfasserIn]
• 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
• Teil: year:2021
• Teil: month:04
• Teil: elocationid:670483
• Teil: pages:1-8
• Teil: 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
• DOI: doi:10.3389/fonc.2021.670483
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: ALK-rearranged non-small-cell lung cancer
• Sach-SW: chemotherapy
• Sach-SW: overall survival
• Sach-SW: Sequential therapies
• Sach-SW: tyrosine kinase inhibitors
• K10plus-PPN: 1756579016
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

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.