Upfront Management of ALK-Rearranged Metastatic Non-small Cell Lung Cancer: One Inhibitor Fits All?

During the past 10 years, multiple ALKi have been developed, and four different compounds are currently available as upfront options for ALK+ NSCLC patients: crizotinib, ceritinib, alectinib, and brigatinib. Second-generation (2G) ALKi demonstrated superior clinical activity in terms of median progression-free survival (mPFS), objective response rate (ORR), intracranial disease control, and duration of response (DOR) when compared with crizotinib. 2G ALKi represent the current gold-standard first-line treatment for ALK-rearranged metastatic NSCLC. Among all available options, in our opinion, alectinib has likely the best profile of clinical activity and safety, thus emerging as the best upfront therapy. More insights will come from ongoing trials and analysis of biomarkers. READ ARTICLE

Current Oncology Reports DOI: 10.1007/s11912-020-00989-6

Authors: Febrizio Tabbò, Francesco Passiglia, Silvia Novello

Review PaperKirk SmithJanuary 1, 2021ALK, NSCLC, TKIs, biomarkers

Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial

"With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank P < .0001; median, 24.0 v 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 v 9.2 months). No new safety concerns emerged. Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC." READ ARTICLE

Journal of Clinical Oncology DOI: http://doi.org/10.1200/JCO.20.00505

Authors: Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, García Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S.

Clinical TrialsKirk SmithNovember 1, 2020clinical trial, ALTA-1L, TKIs, brigatinib, crizotinib

Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review

Anaplastic lymphoma kinase (ALK) inhibitors are important treatment options
for non-small-cell lung cancer (NSCLC), associated with ALK gene rearrangement. Patients
with ALK gene rearrangement show sensitivity to and benefit clinically from treatment with
ALK tyrosine kinase inhibitors (ALK-TKIs). To date, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, and entrectinib have received approval from the US Food and Drug
Administration and/or the European Medicines Agency for use during the treatment of ALKgene-rearrangement forms of NSCLC. Although the oral route of administration is convenient and results in good compliance among patients, oral administration can be affected by
many factors, such as food, intragastric pH, cytochrome P450 enzymes, transporters, and
p-glycoprotein. These factors can result in increased risks for serious adverse events or can
lead to reduced therapeutic effects of ALK-TKIs. This review characterizes and summarizes
the pharmacokinetic parameters and drug–-drug interactions associated with ALK-TKIs to
provide specific recommendations for oncologists and clinical pharmacists when prescribing
ALK-TKIs READ ARTICLE

Drug Design, Development and Therapy DOI:10.2147/DDDT.S249098

Authors: Dehua Zhao, Jing Chen, Mingming Chu, Xiaoqing Long, Jisheng Wang