Feasibility and challenges for sequential treatments in ALK-rearranged non-small-cell lung cancer
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...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 April 2021
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| In: |
Frontiers in oncology
Year: 2021, Volume: 11, Pages: 1-8 |
| ISSN: | 2234-943X |
| DOI: | 10.3389/fonc.2021.670483 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fonc.2021.670483 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fonc.2021.670483/full 
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| Author Notes: | Mei Elsayed, Farastuk Bozorgmehr, Daniel Kazdal, Anna-Lena Volckmar, Holger Sültmann, Jürgen R. Fischer, Mark Kriegsmann, Albrecht Stenzinger, Michael Thomas and Petros Christopoulos |
| Summary: | 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. |
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| Item Description: | Gesehen am 29.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 2234-943X |
| DOI: | 10.3389/fonc.2021.670483 |