Impact of prior ALK-tyrosine kinase inhibitor on pemetrexed-based chemotherapy in patients with advanced ALK positive non-small cell lung cancer

Background: In phase Ⅲ trial comparing crizotinib with chemotherapy in patients with ALK-positive non-small-cell lung cancer (NSCLC) patients, it suggests that pemetrexed is highly effective against ALK-positive NSCLC. However, it is unclear that pemetrexed-based chemotherapy is effective in patients previously treated with ALK-tyrosine kinase inhibitor (ALK-TKI) as well as ALK-TKI naïve patients. Therefore, we investigated the impact of prior ALK-TKI therapy on pemetrexed-based chemotherapy. Conclusions: Pemetrexed-based chemotherapy might be less effective in ALK-positive NSCLC patients previously treated with ALK-TKI. This retrospective study results suggested that ALK-TKI sequence can be a better treatment option in ALK-positive NSCLC patients. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2021.39.15_suppl.e21113

Authors: Michitoshi Yabe, Hirotsugu Kenmotsu, Hiroaki Kodama, Naoya Nishioka, Eriko Miyawaki, Taichi Miyawaki, Nobuaki Mamesaya, Haruki Kobayashi, Shota Omori, Kazushige Wakuda, Akira Ono, Tateaki Naito, Haruyasu Murakami, Toshiaki Takahashi

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

Pediatric low-grade glioma in the era of molecular diagnostics

Low grade gliomas are the most frequent brain tumors in children and encompass a spectrum of histologic entities which are currently assigned World Health Organisation grades I and II. They differ substantially from their adult counterparts in both their underlying genetic alterations and in the infrequency with which they transform to higher grade tumors. Nonetheless, children with low grade glioma are a therapeutic challenge due to the heterogeneity in their clinical behavior – in particular, those with incomplete surgical resection often suffer repeat progressions with resultant morbidity and, in some cases, mortality. The identification of up-regulation of the RAS–mitogen-activated protein kinase (RAS/MAPK) pathway as a near universal feature of these tumors has led to the development of targeted therapeutics aimed at improving responses while mitigating patient morbidity. Here, we review how molecular information can help to further define the entities which fall under the umbrell..... READ ARTICLE

Acta Neuropathologica Communications DOI:10.1186/s40478-020-00902-z

Authors: Scott Ryall, Uri Tabori & Cynthia Hawkins

Safety and efficacy of WX-0593 in ALK-positive or ROS1-positive non-small cell lung cancer

WX-0593 is a potent ALK inhibitor against ALK and ROS1 rearrangement and a series of crizotinib (CRZ)-resistant mutants. We explored the safety and efficacy of WX-0593 in patients (pts) diagnosed with ALK+ or ROS-1+ malignancies, including non-small cell lung cancer (NSCLC). READ ARTICLE

Annals of Oncology DOI:https://doi.org/10.1093/annonc/mdz260.007

Authors: Y-K Shi, J. Fang, S. Zhang, Y. Liu, L. Wang, M. Si, M. Ge and H Geng

Conference PaperKirk SmithOctober 1, 2019WX-0593, ALK+, ROS1, clinical trial

MA21.05 Phase II Trial of the Combination of Alectinib with Bevacizumab in ALK-Positive Nonsquamous Non-Small Cell Lung Cancer

Alectinib is a 2nd generation highly selective anaplastic lymphoma kinase (ALK) inhibitor. Although alectinib has improved progression-free survival (PFS) in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC), there are limited treatment options after progression of alectinib. Recent evidences have described promising results of the combination of bevacizumab with EGFR-TKIs, cytotoxic chemotherapies and immune-checkpoint inhibitors. We report the results from a phase II study of the combination of alectinib with bevacizumab in ALK-positive Nonsquamous NSCLC patients who were treated with alectinib and showed disease progression (UMIN 000017828) READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.676

Authors: S. Watanabe, N. Matsumoto, J. Koshio, A. Ishida, T. Tanaka, T. Abe, D. Ishikawa, S. Shoji, K. Nozaki, K. Ichikawa, R. Kondo, A. Otsubo, A. Aoki, T. Kajiwara, K. Koyama, S. Miura, H. Yoshizawa, T. Kikuchi

Conference PaperKirk SmithOctober 1, 2019alectinib, ALK, Bevacizumab, clinical trial