Population pharmacokinetic (PK) and exposure-response analyses from the pivotal ALTA-1L study: Model-based analyses supporting the brigatinib dose...

Background: Brigatinib is a next-generation ALK tyrosine kinase inhibitor (TKI) with differential activity by dose (90 mg vs 180 mg [with a 7-day lead-in at 90 mg] qd) in the phase 2 post-crizotinib ALTA trial (NCT02094573). Herein, we describe results from population PK and exposure-response analyses of the efficacy and safety of brigatinib 180 mg qd (with a 7-day lead-in at 90 mg) from data in the first-line phase 3 ALTA-1L study (NCT02737501)... Conclusions: These results support a favorable benefit/risk profile of the proposed 180 mg qd brigatinib dose (with a 7-day lead-in at 90 mg) for the front-line treatment of patients with ALK+ NSCLC. Clinical trial information: NCT02737501. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.e21725

Authors: Neeraj Gupta, Karen L. Reckamp, D. Ross Camidge, Huub Jan Kleijn, Aziz Ouerdani, Francesco Bellanti, John Maringwa, Michael J. Hanley, Shining Wang, Pingkuan Zhang, Karthik Venkatakrishnan

Clinical Utility of Cerebrospinal Fluid Cell-Free DNA as Liquid Biopsy for Leptomeningeal Metastases in ALK-Rearranged NSCLC

Introduction: Leptomeningeal metastases (LMs) indicated a poor prognosis in NSCLC. LMs were more frequent in driver gene–mutated patients, and cerebrospinal fluid (CSF) cell-free DNA has shown unique genetic profiles of LM in EGFR-mutated LM. However, studies in patients with ALK receptor tyrosine kinase gene (ALK)-rearranged NSCLC with LMs are scarce. Conclusion: Liquid biopsy of CSF is more sensitive than liquid biopsy of plasma to detect targetable alterations, characterizing resistance mechanisms on progression and monitoring tumor response in patients with ALK-rearranged NSCLC with LM. Thus, CSF might be promising as a medium of liquid biopsy in LM. READ ARTICLE

Journal of Thoracic Oncology
DOI:10.1016/j.jtho.2019.01.007

Authors: Mei-Mei Zheng, Yang-Si Li, Ben-Yuan Jiang, Hai-Yan Tu, Wen-Fang Tang, Jin-Ji Yang, Xu-Chao Zhang, Jun-Yi Ye, Hong-Hong Yan, Jian Su, Qing Zhou, Wen-Zhao Zhong, Xue-Ning Yang, Wei-Bang Guo, Shannon Chuai, Zhou Zhang, Hua-Jun Chen, Zhen Wang, Chao Liu, Yi-Long Wu

Anaplastic Lymphoma Kinase (ALK)-positive Tumors: Clinical, Radiographic and Molecular Profiles, and Uncommon Sites of Metastases in Patients With Lung Adenocarcinoma

Introduction: Anaplastic lymphoma kinase (ALK) gene rearrangements are observed in about 4% to 8% non-small cell lung cancer (NSCLC). ALK+ tumors have been associated with increased pleural and pericardial disease. Our primary objective was to determine the uncommon sites of metastasis of ALK+ NSCLC. Secondary objectives included study of coexisting mutations and factors impacting survival of ALK+ NSCLC. Conclusion: In NSCLC, ALK rearrangements may not be mutually exclusive mutations and can present with unique radiographic patterns. Patients with uncommon sites of metastasis may have worse outcomes. READ ARTICLE

American Journal of Clinical Oncology
DOI:COC.0000000000000508

Authors: Rohan Gupta, Idoroenyi Amanam, Syed Rahmanuddin, Isa Mambetsariev, Yingyu Wang, Charity Huang, Karen Reckamp, Lalit Vora, Ravi Salgia