Dataset Information

Exceptional response to lorlatinib and cabozantinib in ROS1-rearranged NSCLC with acquired F2004V and L2086F resistance.

ABSTRACT: Patients with ROS1-rearranged NSCLC demonstrate excellent disease control with ROS1-targeted therapy, but acquired resistance is inevitable. Of particular interest is the ROS1 L2086F kinase domain mutation which is refractory to all currently available ROS1 TKIs apart from cabozantinib. We present a case of a patient with metastatic ROS1-rearranged NSCLC with dual ROS1 F2004V and L2086F resistance mutations who radiographically responded to the combination of lorlatinib and cabozantinib in a patient with metastatic NSCLC. Furthermore, the patient experienced exceptional clinical improvement and tolerance with the combined use of lorlatinib and cabozantinib. This case builds the case for cabozantinib as an agent to overcome ROS1 L2086F resistance. It also highlights the efficacy and safety of using combination of ROS1 TKIs to overcome complex resistance patterns.

SUBMITTER: Sakamoto M

PROVIDER: S-EPMC10250337 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Exceptional response to lorlatinib and cabozantinib in ROS1-rearranged NSCLC with acquired F2004V and L2086F resistance.

Sakamoto Mandy M Patil Tejas T

NPJ precision oncology 20230608 1

Patients with ROS1-rearranged NSCLC demonstrate excellent disease control with ROS1-targeted therapy, but acquired resistance is inevitable. Of particular interest is the ROS1 L2086F kinase domain mutation which is refractory to all currently available ROS1 TKIs apart from cabozantinib. We present a case of a patient with metastatic ROS1-rearranged NSCLC with dual ROS1 F2004V and L2086F resistance mutations who radiographically responded to the combination of lorlatinib and cabozantinib in a pat ...[more]

PMID: 37291202

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Project description:IntroductionOver the past decade, ALK tyrosine kinase inhibitors have delivered unprecedented survival for individuals with ALK-positive (ALK+) lung cancers. Real-world data enhance the understanding of optimal drug sequencing and expectations for survival.MethodsMulticenter real-world study of individuals with pretreated advanced ALK+ lung cancers managed on a lorlatinib access program between 2016 and 2020. Key outcomes were lorlatinib efficacy, tolerability, and treatment sequencing. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method among all individuals (PFSa and OSa), with at least 30 days (one-cycle) lorlatinib exposure (PFSb and OSb), and with good performance status (PFSc and OSc). Subgroups of interest were analyzed to assess signals of potential clinical applicability. Two OS index dates were analyzed, from lorlatinib initiation and advanced ALK+ diagnosis.ResultsThe population (N = 38, 10 sites) was heavily pretreated (23 had ≥2 previous treatment lines) with a high disease burden (26 had 2-4 sites and 11 had >4 sites of metastatic disease, 19 had brain metastases). The overall response rate was 44% and the disease control rate was 81%. Lorlatinib dose reduction (18%), interruption (16%), and discontinuation (3%) were consistent with the trial experience. From advanced ALK+ diagnosis, the median OS for populations a, b, and c was 45.0 months, 69.9 months and 61.2 months respectively. From lorlatinib initiation, the median PFSa, PFSb and PFSc was 7.3 months, 13.2 months and 27.7 months and the median OSa, OSb and OSc was 19.9 months, 25.1 months and 27.7 months. The median PFSa with versus without brain metastases was 34.6 months versus 5.8 months (p = 0.09). The intracranial median PFS was 14.2 months. Previous good response versus poor response to the first ALK-directed therapy median PFSa was 27.7 months versus 4.7 months with a hazard ratio of 0.3 (p = 0.01).ConclusionsLorlatinib is a potent, highly active brain-penetrant third-generation ALK tyrosine kinase inhibitors with benefits for most individuals in the later-line setting in a real-world evaluation, consistent with clinical trial data.

Dataset Information

Exceptional response to lorlatinib and cabozantinib in ROS1-rearranged NSCLC with acquired F2004V and L2086F resistance.

Publications

Exceptional response to lorlatinib and cabozantinib in ROS1-rearranged NSCLC with acquired F2004V and L2086F resistance.

Similar Datasets

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