Association of anaplastic lymphoma kinase variants and alterations with ensartinib response duration in non-small cell lung cancer

Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression-free survival (PFS). We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. Our study showed that secondary ALK alterations were adversely associated with ensartinib efficacy, and that ALK variants might not correlate with PFS. The quantitative radiomic signature provided added prognostic prediction value to the clinicopathological features. READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.14083

Authors: Donghui Hou, Xiaomin Zheng, Wei Song, Xiaoqing Liu, Sicong Wang, Lina Zhou, Xiuli Tao, Lv Lv, Qi Sun, Yujing Jin,Zewei Zhang, Lieming Ding, Ning Wu, Shijun Zhao

The landscape of ALK alterations in non-small cell lung cancer

Most ALK variants are described as VUS, limiting the
impact of precision oncology. ALK fusions occur in 2.6%% of the lung adenocarcinomas, with EML4 being the most common upstream partner.
Meanwhile, G1202R mutations occur only among 0.07% of the ALK alterations. Heat shock protein and Neuregulin-1 pathway may present additional opportunities for combination targeted therapies in the future for ALK-positive NSCLC. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/S1556-0864(21)01863-3

Authors: A. Desai, T. Mohammed, S. Rakshit, J. Krull

Real-World OutcomesKirk SmithApril 1, 2021ALK variants

ALK variants, PD-L1 expression, and their association with outcomes in ALK-positive NSCLC patients

It remains unclear how programmed death-ligand 1 (PD-L1) expression interacts with anaplastic lymphoma kinase (ALK) mutation, its variants, and the outcome of treatment. One hundred and twenty four out of 1255 patients (9.9%) were deemed ALK-positive by the Ventana IHC assay. PD-L1 status and ALK variants were available in 100 and 59 patients, respectively. PD-L1 positive (TPS ≥ 1%) and strong positive (TPS ≥ 50%) rate was 50% and 16%, respectively. A total of 64 variant types were detected in 59 patients. V1 (32.8%) and V3a/b (28.1%) were the most common variants. There was no significant association between ALK variants and the PD-L1 expression. The presence of V3a/b subtype independently predicted a worse overall survival in patients receiving ALK inhibitor(s) (aHR 5.10 [95% CI 1.22–21.25], P = 0.025) and platinum plus pemetrexed (aHR 9.62 [95% CI 1.90–48.80], P = 0.006). While incorporating ALK variants and PD-L1 expression together, patients with non-V3a/b/positive PD-L1 showed a ..... READ ARTICLE

Nature DOI: 10.1038/s41598-020-78152-1

Authors: Manasi K. Mayekar, View ORCID ProfileDeborah R. Caswell, Natalie I. Vokes, Emily K. Law, Wei Wu, William Hill, Eva Gronroos, Andrew Rowan, Maise Al Bakir, Caroline E. McCoach, Collin M. Blakely, Nuri Alpay Temiz, Ai Nagano, D. Lucas Kerr, Julia K. Rotow, Franziska Haderk, Michelle Dietzen, Carlos Martinez Ruiz, Bruna Almeida, Lauren Cech, Beatrice Gini, Joanna Przewrocka, Chris Moore, Miguel Murillo, Bjorn Bakker, Brandon Rule, Cameron Durfee, Shigeki Nanjo, Lisa Tan, Lindsay K. Larson, Prokopios P. Argyris, William L. Brown, Johnny Yu, Carlos Gomez, Philippe Gui, Rachel I. Vogel, Elizabeth A. Yu, Nicholas J. Thomas, Subramanian Venkatesan, Sebastijan Hobor, Su Kit Chew, Nnennaya Kanu, Nicholas McGranahan, Eliezer M. Van Allen, Julian Downward, Reuben S. Harris, Trever G. Bivona, Charles Swanton

Real-World OutcomesKirk SmithDecember 1, 2020ALK variants, PD-L

Abstract CT025: Impact of the EML4-ALK fusion variant on the efficacy of lorlatinib in patients (pts) with ALK-positive advanced non-small cell lung cancer (NSCLC)

In this heavily pretreated group of ALK+ NSCLC pts, the presence of an ALK resistance mutation might enrich for EML4-ALK variants 1 and 3. Lorlatinib exhibited antitumor activity irrespective of EML4-ALK variant and across a variety of ALK resistance mutations. READ ARTICLE

AACR abstract. DOI: 10.1158/1538-7445.AM2020-CT025

Authors: Todd M. Bauer, Jean-François Martini, Benjamin Besse, Chia-Chi Lin, Ross A. Soo, Gregory J. Riely, Sai-Hong Ignatius Ou, Francesca Toffalorio, Antonello Abbattista, Holger Thurm, D. Ross Camidge, Steven Kao, Rita Chiari, Shirish Gadgeel, Enriqueta Felip, Alice T. Shaw, Benjamin J. Solomon

Real-World OutcomesKirk SmithAugust 1, 2020lorlatinib, ALK variants

Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non–Small Cell Lung Cancer in the Global Phase III ALEX Study

Alectinib continues to demonstrate superior investigator-assessed PFS versus crizotinib in untreated ALK-positive NSCLC, irrespective of EML4-ALK variant. READ HERE

Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2019.03.007

Authors: D. Ross Camidge, Rafal Dziadziuszko, Solange Peters, Tony Mok,Johannes Noe, Malgorzata Nowicka, Shirish M. Gadgeel, Parneet Cheema, MD, Nick Pavlakis, Filippo de Marinis, Byoung Chul Cho, Li Zhang, Denis Moro-Sibilot, Ting Liu, Walter Bordogna, Bogdana Balas, Barbara Müller,Alice T. Shaw

Clinical TrialsKirk SmithMarch 1, 2019ALEX Study, alectinib, ALK variants