Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis

Anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK-positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients. We find that neutropenia under crizotinib treatment was found to be associated with improved PFS suggesting that neutropenia might be an important determinant in treatment and survival strategies. READ ARTICLE

Indian Journal of Cancer DOI:10.4103/ijc.IJC_71_20

Authors: Pınar Gürsoy, Burcu Çakar, Deniz Nart, Erdem Göker

Real-World OutcomesKirk SmithSeptember 30, 2021ALK, NSCLC, crizotinib, AE, neutropenia, PFS

Outcomes of KRAS mutated, EGFR mutated, ALK mutated and wildtype patients in non-small cell lung cancer brain metastases

Background: Non-small cell lung cancer (NSCLC) is the most common primary tumor leading to brain metastases. Multiple genetic markers have been profiled in NSCLC patients for potential targeted therapies. EGFR is mutated in up 50% of NSCLCs, while ALK is mutated in around 4-7%. KRAS is the most commonly overexpressed marker, seen in up to 85% of all lung cancers. In this retrospective study, we evaluated the overall survival (OS) and progression-free survival (PFS) between NSCLCBM patients with KRAS mutations, ALK mutations, EGFR mutations, and wildtype. Conclusions: Molecular mutations serve as both prognostic predictors and alternative targeted therapies for NSCLCBM treatment. Our retrospective study showed improved mOS and mPFS in NSCLCBM patients with ALK rearrangements when compared to patients with EGFR mutations, KRAS mutations, and the wildtype. While these results looked at patient outcomes with specific tumor markers, further investigation needs to be done regarding outcomes..... READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2021.39.15_suppl.e21028

Authors: Yasmeen Rauf, Vineeth Tatineni, Patrick joseph Oshea, Xuefei Jia, David M. Peereboom, Manmeet Singh Ahluwalia

Conference PaperKirk SmithMay 28, 2021non-small cell lung cancer (NSCLC), mutations, PFS

Low ALK FISH positive metastatic non-small cell lung cancer (NSCLC) patients have shorter progression-free survival after treatment with ALK inhibitors

ALK FISH assay guides clinical decision to initiate therapy with ALK inhibitors in patients with stage IV non-small cells lung cancer (NSCLC). In this single institution retrospective study, we investigated the association between the strength of ALK positivity and progression-free survival (PFS) We screened 4,829 patients tested for ALK rearrangement by FISH from 01/06/2012 to 06/30/2018 and included 66 stage IV NSCLC ALK positive patients, who were ALK inhibitor naïve, received an ALK inhibitor, and been followed at least 10 months to the study. The median PFS for cases high positive cases [≥=50% positive nuclei; n = 49] and low positive cases [16–49% positive nuclei; n = 17] is 16 months and 4 months respectively, and the hazard ratio is 2.89 [95 CI 1.34–6.2] (p = 0.0068). When cases are stratified according to cut-off ≥=30% positive nuclei, the median PFS for cases above (n = 55) and below the cut-off (n = 11) is 12 and 3 months, respectively and the hazard ratio is 9.60 [95 CI 2.6..... READ ARTICLE

Cancer Genetics DOI:10.1016/j.cancergen.2019.12.003

Authors: Gokce A. Toruner, Zhenya Tang, Guilin Tang, L. Jeffrey Medeiros, Shimin Hu

Case StudyKirk SmithDecember 12, 2019ALK, FISH, PFS, Lung cancer

Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer

Objectives: The J-ALEX study compared the efficacy and safety of alectinib with crizotinib in Japanese patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). Superiority in independent review facility (IRF)-assessed progression-free survival (PFS) was demonstrated for alectinib at the second pre-planned interim PFS analysis (data cutoff: December 3, 2015; hazard ratio [HR] 0.34, 99.7 % confidence interval [CI]: 0.17–0.71, P < 0.0001). We report final PFS data and the second pre-planned interim analysis of overall survival (OS) and safety (data cutoff: June 30, 2018). Conclusions: At the final PFS analysis, alectinib continued to demonstrate superiority in IRF-assessed PFS versus crizotinib in ALK-inhibitor-naïve ALK-positive NSCLC, with a favorable safety profile. OS follow-up continues. READ ARTICLE

Lung Cancer. DOI: 10.1016/j.lungcan.2019.11.025

Authors: Kazuhiko Nakagawa, Toyoaki Hida, Hiroshi Nokihara, Masahiro Morise, Koichi Azuma, Young Hak Kim, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Toru Kumagai, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Miyako Satouchi, Toshiyuki Kozuki, Ryo Koyama, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Takashi Asakawa, Morihiko Hayashi, Wakako Hasegawa, Tomohide Tamura

Clinical TrialsKirk SmithNovember 28, 2019Alectinib, ALK-positive, Crizotinib, J-ALEX, NSCLC, PFS

EP101-35 Concurrent Use of Low Dose Aspirin and Vitamin D in ALK, ROS and EGFR Mutant NSCLC: A Single Institution Retrospective Analysis

Recent meta-analysis published by Feng et al. analyzed seventeen studies and reported statistically significant reduction in risk of lung cancer by 8% when circulating 25-VD is at 10 nmol/L, this benefit was seen in both Caucasian and Asian population. To our knowledge, there have been no studies looking at influence of concurrent vitamin D or aspirin intake on outcomes in ALK, ROS and EGFR pos NSCLC treated with tyrosine kinase inhibitors. We performed a retrospective single institution analysis to study this association.Patients (pts) with ALK, ROS EGFR pos NSCLC treated with first line TKI from January 2014 to June 2017 were included. Information on concurrent use and doses of aspirin and vitamin D supplements were studied. Patients were dichotomized based on use of these individual supportive medications. Two sample t-test was used to compare mean PFS and chi-square test to compare proportions of disease control rate (DCR) at 3 months between groups.Our study did not show any diffe..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2008

Authors: C. Bernabe, S. Sharma, J. Sanchez, K. Sullivan, N. Seetharamu

Conference PaperKirk SmithOctober 1, 2019PFS, DCR, EGFR, ROS, ALK positive, NSCLC, vitamin D, aspirin, TKI

Short progression-free survival of ALK inhibitors sensitive to secondary mutations in ALK-positive NSCLC patients

Most non-small cell lung cancer (NSCLC) patients relapse on anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) therapy because of acquired resistance. Rebiopsy is recommended to provide optimal therapy after relapse for some ALK-TKI therapies; however, little clinical data exists on the clinical efficacy of ALK-TKI tailored to secondary mutation. READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.13143

Authors: Naoki Haratake, Takashi Seto, Shinkichi Takamori, Ryo Toyozawa, Kaname Nosaki, Naoko Miura, Taro Ohba, Gouji Toyokawa, Kenichi Taguchi, Masafumi Yamaguchi, Mototsugu Shimokawa, Mitsuhiro Takenoyama