The Effect of Rifampin on the Pharmacokinetics and Safety of Lorlatinib: Results of a Phase One, Open-Label, Crossover Study in Healthy Participants

Introduction: Lorlatinib is a third-generation tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer; cytochrome P450 (CYP) 3A plays an important role in the metabolism of lorlatinib. Conclusions: The addition of a single dose of lorlatinib to daily dosing with rifampin significantly reduced lorlatinib plasma exposure relative to a single dose of lorlatinib administered alone and was associated with severe but self-limiting transaminase elevations in all healthy participants. These observations support the contraindication in the product label against concomitant use of lorlatinib with all strong CYP3A inducers. READ ARTICLE

Advances in Therapy DOI:10.1007/s12325-019-01198-9

Authors: Joseph Chen, Huiping Xu, Sylvester Pawlak, Leonard P. James, Gerson Peltz, Kimberly Lee, Katherine Ginman, Michelle Bergeron & Yazdi K. Pithavala

Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer

Objectives: A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here. Conclusion: Updated results from this pooled analysis further demonstrate that alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2019.10.015

Authors: Sai-Hong Ignatius Ou, Shirish M. Gadgeel, Fabrice Barlesi, James Chih-Hsin Yang, Luigi De Petris, Dong-Wan Kim, Ramaswamy Govindan, Anne-Marie Dingemans, Lucio Crino, Hervé Léna, Sanjay Popat, Jin Seok Ahn, Eric Dansin, Emmanuel Mitry, Barbara Müller, Walter Bordogna, Bogdana Balas, Peter N. Morcos, Alice T. Shaw

Clinical TrialsKirk SmithOctober 14, 2019Alectinib, ALK+, NSCLC, Overall survival, Pooled analysis, Safety

EP101-62 The Safety Profile and Preliminary Efficacy of Ceritinib 450mg with Food in Chinese ALK/ROS-1 Positive NSCLC Patients

Ceritinib have shown potent efficacy in both ALK and ROS-1 rearranged NSCLC. However, high rate of treatment interruption was suffered due to gastrointestinal or liver toxicity using Ceritinib 750mg fasting in previous study. Recently, ASCEND-8 study reported an improved tolerance and a trend to better efficacy with 450mg with food, but little data is available in Chinese patients. This first-time real-world study aims to assess the safety profile and preliminary efficacy of Ceritinib 450mg with food in Chinese patients. From Oct 2018 to March 2019, 51 ALK or ROS1 positive NSCLC patients received ceritinib were enrolled from 8 centers in Sichuan province. Safety profile and preliminary efficacy were retrospectively analyzed. The follow-up was to 31st March 2019. The study found Ceritinib 450mg with food demonstrated a good safety profile and efficacy with lower AE incidence rate and better compliance rate compare to ASCEND-8 data for Chinese patients in real-world setting...... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2035

Authors: Y. Tian, P. Yu, X. Yin, K. Wang, M. Huang, Y. Wang, Y. Gong, J. Li