Discusses risks and benefits of adjuvant therapy for treatment of earlier stage and locoregional lung cancer; advocates genome sequencing of earlier stage lung cancer. READ ARTICLE
Translational Lung Cancer Research DOI: 33569340
Authors: Reyes, Roxana, Reguart, Noemi
Read MoreThe real-world intracranial efficacy data of ceritinib at a dose of 450mg QD are still unavailable, thus this study aims to analyze the intracranial efficacy of ceritinib (450mg QD) in ALK-rearrangement NSCLC patients in China. Conclusion Ceritinib administered at a dose of 450mg QD to ALK-rearrangement NSCLC patients with BM in China demonstrates superior ORR and DCR, as well as PFS and EFP that are expected to be improved. Especially the estimated 12-month EFP of intracranial lesions was improved in patients with prior brain radiotherapy. READ ARTICLE
European Society for Medical Oncology. DOI:10.1016/j.annonc.2020.10.386
Authors: Z. Qiu, , K. Wang, M. Huang, M. Yu, C. Liu, X. Xian
This descriptive, retrospective observational study used the Japan Medical Data Vision Co., Ltd. (MDV), database (June 2017–November 2018) and covered data for EGFR, ALK, ROS1, and PD-L1; records on BRAF testing were not yet available. This real-world evidence revealed variations in diagnostic testing patterns, which could affect time to treatment in Japan. Variations are likely influenced by individual biomarker prioritization considering limited tissue samples in clinical practice. READ ARTICLE
Journal of Thoracic Oncology DOI: 10.1016/j.jtocrr.2020.100136
Authors: Yasushi Yatabe, Yasumasa Yoshiki, MPH, Koichi Matsumura, Kanae Togo, MSc, Hironori Kikkawa, Laura Iadeluca, MPH, Benjamin Li, Kazuto Nishio,
Read MoreqRT-PCR successfully identified EML4-ALK fusion rearrangement in direct smear preparations of lung adenocarcinoma. Direct smear samples can be used for EML4-ALK rearrangement detection using qRT-PCR. The EML4-ALK rearrangement gene has high prevalence in selected lung adenocarcinoma and EGFR mutation-negative populations. ALK inhibitors in lung cancer can be openly considered for use in Indonesian patients to improve the outcome of this subset of patients. READ ARTICLE
Pulmonary Medicine DOI:10.1155/2020/3578748
Authors: Didik S. Heriyanto, Ika Trisnawati, Evan G. Kumara, Vincent Laiman, Fara S. Yuliani, Auliya S. B. Sumpono, Rita Cempaka, Marcellus, Eko Budiono
Patients with ALK-mutant advanced lung adenocarcinoma have the highest rate of TE. TE is associated with worse survival across molecular subtypes. These findings should be taken into consideration in decision-making regarding thromboprophylaxis. READ ARTICLE
Journal of Thrombosis and Haemostasis DOI:doi.org/10.1111/jth.15215
Authors: Joanna Roopkumar,Shyam K. Poudel,Lorenzo Gervaso,Chandana A. Reddy,Vamsidhar Velcheti,Nathan A. Pennell,Keith R. McCrae,Alok A. Khorana
The objective response rate and median progression-free survival to crizotinib treatment tended to be better in complex ALK fusion patients.
Notably, patients with complex ALK fusions had significantly improved overall survival after crizotinib treatment especially when compared with the pure canonical EML4-ALK fusion group.
The complex ALK fusion group also tended to respond better to next-generation ALK TKIs, which were used as later-line therapies.
Most identified non-canonical ALK fusions were likely to be expressed in tumors, and some of them formed canonical EML4-ALK transcripts during mRNA maturation.
Diagnosis using CGP is of great value to identify novel ALK fusions and predict prognosis. READ ARTICLE
Frontiers in Oncology DOI: 10.3389/fonc.2020.596937
Authors: Jin Kang,Xu-Chao Zhang,Hua-Jun Chen, Wen-Zhao Zhong, Yang Xu, Jian Su, Qing Zhou, Hai-Yan Tu, Zhen Wang, Chong-Rui Xu, Xue-Ning Yang, Zhi-Hong Chen, Xue Wu, Xian Zhang, Yang Shao, Yi-Long Wu, Jin-Ji Yang
Read MoreIn conclusion, image evaluation strategy with RECIST for patients with lung cancer has difficulty in obtaining the appropriate quantity of diffuse lung nodules, pleural effusions, and bone metastases. The type of 4-TMpc after 14 days TKI targeted therapy is associated with image response and PFS without accounting for mutation status in advanced lung adenocarcinoma patients. Our study results could help early therapeutic decision making by identifying patients who may benefit from gefitinib, erlotinib, afatinib, crizotinib, or ceritinib 14 days after TKI targeted therapy.status, in patients with advanced lung adenocarcinoma. READ ARTICLE
PLOS ONE DOI: 10.1371/journal.pone.0240736
Authors: Chen H-J, Tu C-Y, Huang K-Y, Chien C-R, Hsia T-C
Read MoreSince then, subsequent generations of ALK inhibitors have demonstrated superior efficacy and better CNS activity compared to crizotinib. Alectinib and brigatinib, both second-generation ALK inhibitors have been compared directly to crizotinib in the first-line setting and has demonstrated improved progression free survival (PFS) and intracranial response. Ceritinib, another second-generation ALK inhibitor has been shown to be superior to chemotherapy in ALK-rearranged disease with good CNS activity. Initial responses to ALK inhibitors are not always durable and resistance can occur as on-target or off-target alterations. Lorlatinib, a third-generation ALK inhibitor, has demonstrated activity in the treatment naïve setting and in resistance to crizotinib and second-generation ALK inhibitors. Lorlatinib has also shown improved PFS in patients harboring EML4-ALK variant 3, which is associated with the development of ALK resistance mutations, specifically G1202R. Another new ALK inhibitor, ensartinib, has demonstrated efficacy in the first-line setting and in alectinib refractory disease. READ ARTICLE
Translational Lung Cancer Research DOI: 10.21037/tlcr-20-331
Authors: Bing Xia, Misako Nagasaka, Viola W. Zhu, Sai-Hong Ignatius Ou, Ross A. Soo
Read MoreThe bedrock of resistance to TKI is that, after the diagnosis, we face with a different disease that needs to be re-characterized through tissue or/and liquid biopsies. Understanding molecular pathways driving the resistant phenotype will give us the chance to know what we are dealing with and, rather than choose an empirical approach, will help us to properly define the best targeted treatment for these patients. READ ARTICLE
Translational Lung Cancer Research DOI: 10.21037/tlcr-20-372
Authors: Tabbò F, Reale ML, Bironzo P, Scagliotti GV.
Read MoreThere was no significant decrease in HUS when patients with ALK+ disease were treated longitudinally with each TKI, as long as patients were clinically stable. Alectinib, brigatinib, and lorlatinib had the best toxicity profiles and exhibited high mean HUS longitudinally in the real-world setting. READ ARTICLE
Current Oncology DOI: 10.3747/co.27.6563
Authors: Tse BC, Said BI, Fan ZJ, Hueniken K, Patel D, Gill G, Liang M, Razooqi M, Brown MC, Sacher AG, Bradbury PA, Shepherd FA, Leighl NB, Xu W, Howell D, Liu G, O'Kane G.
Read MoreNew Dose Strategy for Ceritinib May Improve Outcomes in ALK-Positive NSCLC READ ARTICLE
ESMO DOI: 10.1016/j.annonc.2020.10.386
Authors: Z. Qiu, K. Wang, M. Huang, M. Yu, C. Liu, X. Xian
Read MoreIt 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
Read MoreObjectives Lorlatinib is a potent 3rd generation anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with ALK positive advanced non-small cell lung cancer (NSCLC) previously treated with one or more ALK tyrosine kinase inhibitors (TKIs). The present study assessed the cost-effectiveness of Lorlatinib versus pemetrexed with platinum combination of carboplatin or cisplatin (platinum based ChT) in Greece.Conclusions The present analysis suggests that Lorlatinib may be considered a cost-effective option over platinum based ChT in Greece, for the treatment of patients with ALK positive advanced NSCLC who have progressed after one or more ALK TKIs, while covering a significant unmet medical need. READ ARTICLE
Value in Health DOI:10.1016/j.jval.2020.08.244
Authors: G. Gourzoulidis, O. Zisimopoulou, N. Boubouchairopoulou, C. Michailidi, C. Almond, C. Tzanetakos, G. Kourlaba,
Lung cancer is the leading causes of cancer-related death worldwide. Precise treatment based on next-generation sequencing technology has shown advantages in the diagnosis and treatment of lung cancer. This cohort study included 371 lung cancer patients. The lung cancer subtype was related to the smoking status and sex of the patients. The most common mutated genes were TP53 (62%), EGFR (55%), and KRAS (11%). The mutation frequencies of EGFR, TP53, PIK3CA, NFE2L2, KMT2D, FGFR1, CCND1, and CDKN2A were significantly different between lung adenocarcinoma and lung squamous cell carcinoma. We identified the age-associated mutations in ALK, ERBB2, KMT2D, RBM10, NRAS, NF1, PIK3CA, MET, PBRM1, LRP2, and CDKN2B; smoking-associated mutations in CDKN2A, FAT1, FGFR1, NFE2L2, CCNE1, CCND1, SMARCA4, KEAP1, KMT2C, and STK11; tumor stage-associated mutations in ARFRP1, AURKA, and CBFB; and sex-associated mutations in EGFR. Tumor mutational burden (TMB) is associated with tumor subtype, age, sex, and s..... READ ARTICLE
Scientific Reports DOI:10.1038/s41598-020-76791-y
Authors: Yanhong Shang, Xiaofang Li, Weiwei Liu, Xiaoliang Shi, Shaohua Yuan, Ran Huo, Guotao Fang, Xiao Han, Jingnan Zhang, Kunjie Wang, Zhengyue Dou, Yan Zhang, Aimin Zang and Lin Zhang
Recurrent/metastatic (R/M) head and neck cancers bear a poor prognosis. In this analysis, we examined the efficacy and the outcome of targeted therapy recommendations based on the patients’ molecular tumor portrait after failure of all standard therapy options. In this single-center, real-world retrospective analysis of our platform for precision medicine, we analyzed the molecular profile of 50 patients diagnosed with R/M head and neck cancer. Tumor samples of the patients were examined using next-generation sequencing panels of mutation hotspots, microsatellite instability (MSI) testing, and immunohistochemistry (IHC). In 31 cases (62.0% of all patients), a molecular-driven targeted therapy approach was recommended. Eventually, 14 patients (28%) received the suggested targeted therapy. Six of fourteen patients (43%) achieved stable disease conditions and four patients (29%) experienced a progressive disease. The median time to treatment failure was 2.8 months. Therapy recommendations were significantly more often issued for men (p = 0.037) than for women. This analysis demonstrated that precision medicine provided the basis for molecular-driven therapy recommendations in over half of the patients with advanced therapy refractory head and neck cancers, with significantly more therapy recommendations for men. Our analysis showed that although precision medicine approaches are implementable and feasible for the management of recurrent/metastatic head and neck cancers in daily clinical routine, there are major limitations and challenges that have to be overcome. READ ARTICLE
Cancers DOI: 10.3390/cancers12113381
Authors: Hossein Taghizadeh, Robert M. Mader, Leonhard Müllauer, Thorsten Fuereder, Alexandra Kautzky-Willer and Gerald W. Prager
Read MoreIn clinical practice, patients with anaplastic lymphoma kinase (ALK)-rearrangement–positive non–small-cell lung cancer commonly receive sequential treatment with ALK tyrosine kinase inhibitors. The third-generation agent lorlatinib has been shown to inhibit a wide range of ALK resistance mutations and thus offers potential benefit in later lines, although real-world data are lacking. This multicenter study retrospectively investigated later-line, real-world use of lorlatinib in patients with advanced ALK- or ROS1-positive lung cancer. Fifty-one patients registered in a compassionate use program in Austria, who received second- or later-line lorlatinib between January 2016 and May 2020, were included in this retrospective real-world data analysis. Median follow-up was 25.3 months. Median time of lorlatinib treatment was 4.4 months for ALK-positive and 12.2 months for ROS-positive patients. ALK-positive patients showed a response rate of 43.2%, while 85.7% percent of the ROS1-positive pa.....READ ARTICLE
Pharmaceuticals DOI: 10.3390/ph13110371
Author: Maximilian J. Hochmair, Hannah Fabikan ,Oliver Illini, Christoph Weinlinger ,Ulrike Setinek, Dagmar Krenbek , Helmut Prosch , Markus Rauter ,Michael Schumacher ,Ewald Wöll ,Romana Wass ,Elmar Brehm ,Gudrun Absenger , Tatjana Bundalo , Peter Errhalt , Matthias Urban and Arschang Valipour
Read MoreBackground: ... We assessed clinical utility of ctDNA NGS for ALK testing for non-Sq-NSCLC in Asia... Conclusions: NGS testing for ALK fusions and genomic alterations in plasma ctDNA has clinical utility in non-Sq-NSCLC patients in guiding ALK targeted treatment at initial diagnosis and upon cancer progression. Detection rate and distribution of ALK fusion partners are comparable to existing data of tumor ALK testing. Further data on ALK treatment outcomes of patients with detectable ALK fusion on plasma ctDNA is warranted. READ ARTICLE
Annals of Oncology DOI:10.1016/j.annonc.2020.10.300
Authors: K. W. C. Lee, S. T. Wu, P. Y. Lo, C. T. Choy, T. C. Kwong, Y. T. N. Lau, L. Lin, S. W. Lau
Background: Anaplastic lymphoma kinase (ALK) have been recognized as the most important predictor of response to crizotinib. However, 20-30% of patients harboring ALK fusion non-small-cell lung cancer patients show a poor response requiring investigation for underlying mechanisms... Conclusions: BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN, PIK3CA mutations), SMARCA4 mutations or EML4-ALK fusion (non A20) might contribute to molecular mechanisms of primary resistance to crizotinib in ALK+NSCLC.Further investigations are warranted to overcome these primary resistance. READ ARTICLE
Annals of Oncology DOI:10.1016/j.annonc.2020.10.404
Authors: W-X. Wang, C. Xu, Q-X. Zhang, W. Zhuang, Z-B. Song, Y-C. Zhu, G. Chen, M-Y. Fang, T-F. Lv, Y. Song
Background: The aim of this study was to determine the demographic prole ofdriver gene alterations, especially low-frequency gene alterations in Chinesepatients with non-small cell lung cancer (NSCLC).Methods: A total of 7395 Chinese patients with NSCLC were enrolled in thestudy. Next-generation sequencing (NGS) was performed on formalin-xedparafn-embedded specimens collected via either surgical resection or biopsy.Results: The frequent genomic alteration s found in the study were EGFR muta-tions (51.7%), KRAS mutations (13.1%), MET alterations (5.6%; 3.2% copy num-ber gains and 0.5% exon 14 skipping mutation), HER2 alterations (7.0%; 2.0%copy number gains and 5.4% mutations), ALK alterations (7.2%; 3.9%rearrangements), RET rearrangements (1.4%), ROS1 rearrangements (0.9%), andNTRK rearrangements (0.6%). The EGFR mutation rate was found to be signi-cantly higher in women than in men (69.1% vs. 38.5%, P < 0.001), while theKRAS mutation (17.5% vs. 7.3%, P < 0.001) and MET alteration ..... READ ARTICLE
Thoracic Cancer DOI:10.1111/1759-7714.13757
Authors: Xiaoyan Si, Ruili Pan, Shaohua Ma, Lin Li, Li Liang, Ping Zhang, Yuping Chu, Hanping Wang, Mengzhao Wang, Xiaotong Zhang, Li Zhang
Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib... Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ± 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ± 24 months is unprecedented for ROS1(+) NSCLC. READ ARTICLE
Lung Cancer DOI:10.1016/j.lungcan.2020.07.022
Authors: Nir Peled, Roni Gillis, Saadettin Kilickap, Patrizia Froesch, Sergei Orlov, Elena Filippova, Umut Demirci, Petros Christopoulos, Irfan Cicin, Fatma Bugdayci Basal, Cengiz Yilmaz, Moiseenko Fedor, Taner Korkmaz, Semra Paydas, Oliver Gautschi, Alisan Zirtiloglu, Yesim Eralp, Havva Yesil Cinkir,… Laila C. Roisman
