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Case Report

Acquired G2032R Resistance Mutation in ROS1 to Lorlatinib Therapy Detected with Liquid Biopsy

1
Lung Cancer Network NOWEL, 26129 Oldenburg, Germany
2
Institute for Hematopathology Hamburg, Fangdieckstraße 75A, 22547 Hamburg, Germany
3
Department of Hematology and Oncology, Pius-Hospital Oldenburg, Georgstraße 12, 26121 Oldenburg, Germany
4
Department of Internal Medicine-Oncology, University of Oldenburg, Georgstraße 12, 26121 Oldenburg, Germany
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2022, 29(9), 6628-6634; https://doi.org/10.3390/curroncol29090520
Received: 30 August 2022 / Revised: 13 September 2022 / Accepted: 14 September 2022 / Published: 16 September 2022
Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK)/receptor tyrosine kinase inhibitor (ROS1), demonstrated efficacy in ROS1 positive (ROS1+) non-small cell lung cancer (NSCLC), although approval is currently limited to the treatment of ALK+ patients. However, lorlatinib-induced resistance mechanisms, and its efficacy against the resistance mutation G2032R in ROS1, respectively, have not yet been fully understood. Furthermore, concomitant tumor suppressor gene p53 (TP53) mutations occur in driver alteration positive NSCLC, but their prognostic contribution in the context of ROS1 inhibition remains unclear. Here we report a ROS1+ NSCLC patient who developed an on target G2032R resistance mutation during second-line lorlatinib treatment, indicating the lack of activity of lorlatinib against ROS1 G2032R. The resistance mutation was detected in plasma-derived ctDNA, signifying the clinical utility of liquid biopsies. View Full-Text
Keywords: NSCLC; lorlatinib; ROS1; resistance mutation; liquid biopsy; G2032R NSCLC; lorlatinib; ROS1; resistance mutation; liquid biopsy; G2032R
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MDPI and ACS Style

Jóri, B.; Falk, M.; Hövel, I.; Weist, P.; Tiemann, M.; Heukamp, L.C.; Griesinger, F. Acquired G2032R Resistance Mutation in ROS1 to Lorlatinib Therapy Detected with Liquid Biopsy. Curr. Oncol. 2022, 29, 6628-6634. https://doi.org/10.3390/curroncol29090520

AMA Style

Jóri B, Falk M, Hövel I, Weist P, Tiemann M, Heukamp LC, Griesinger F. Acquired G2032R Resistance Mutation in ROS1 to Lorlatinib Therapy Detected with Liquid Biopsy. Current Oncology. 2022; 29(9):6628-6634. https://doi.org/10.3390/curroncol29090520

Chicago/Turabian Style

Jóri, Balázs, Markus Falk, Iris Hövel, Peggy Weist, Markus Tiemann, Lukas C. Heukamp, and Frank Griesinger. 2022. "Acquired G2032R Resistance Mutation in ROS1 to Lorlatinib Therapy Detected with Liquid Biopsy" Current Oncology 29, no. 9: 6628-6634. https://doi.org/10.3390/curroncol29090520

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