Special issue "The advance of solid tumor research in China": Real-world clinical outcomes of alectinib for advanced non-small-cell lung cancer patients with ALK fusion in China.

Global phase 3 trials have demonstrated the priority of several next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). However, clinical studies are conducted with specific populations that differ from the real world. The study aimed to evaluate the clinical outcomes of alectinib in real-world settings. Patients with advanced non-small-cell lung cancer (NSCLC) and EML4-ALK fusion were enrolled from two medical centers between June 2018 and June 2020. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) to alectinib. The secondary endpoint was response of brain metastases. The risk factors for disease progression were also investigated. In total, 127 patients with advanced NSCLC were enrolled into this study. Of them, 54.3% received first-line alectinib. The 1- and 2-year PFS rates were 77.4% and 68.3%, respectively. ORR and disease control rate (DCR) were 53.5% and 91.3%, respectively. Among patients with brain metastases, intracranial ORR and DCR were 63.6% and 88.6%, respectively. In addition, we found that "crizotinib pretreatment", "liver metastasis", and "TP53 co-mutation" were individually associated with shorter PFS in alectinib treatment. In conclusion, this study confirms the salient clinical outcomes of alectinib for ALK-fusion-driven NSCLC patients with or without brain metastases, adding real-world evidence to the priority of alectinib in clinical practice. READ ARTICLE

Int J Cancer DOI:10.1002/ijc.34123

Authors: Su C, Zhou J, Qiang H, Zhao J, Chang Q, Ji X, Li J, Xie M, Chu T.

Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases

Purpose: The performance of alectinib and crizotinib in untreated anaplastic lymphoma kinase (ALK)-positive patients with non-small-cell lung cancer (NSCLC) and symptomatic and synchronic brain metastases is largely unknown. This retrospective study assessed the effectiveness of alectinib and crizotinib, together with intracranial therapies in a cohort of these patients.
Patients and Methods: This study included 34 previously untreated ALK-positive NSCLC patients with three or fewer intracranial metastases. Of these patients, 13 received oral alectinib 600 mg twice daily, and 21 received oral crizotinib 250 mg twice daily, until progressive disease, unacceptable toxicity, or death. All intracranial metastases were treated with craniotomy, CyberKnife, or both.
Results: Median overall progression-free survival (PFS) was 32.8 months (95% CI 24.4– 41.2 months) in patients treated with alectinib and 8.0 months (95% CI 7.3– 8.7 months) in patients treated with crizotinib. Median PFS of brain..... READ ARTICLE

Onco Targets Therapy DOI:10.2147/OTT.S345439

Authors: Yin Q, Li P, Wang P, Zhang Z, Liu Q, Sun Z, Li W, Ma L, Wang X

Intracranial remission with brigatinib rechallenge as fifth-line ALK inhibition therapy in a lung cancer patient

Several anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors have been developed for the treatment of EML4-ALK-rearranged non-small-cell lung cancer, with the newer generation agents brigatinib, alectinib and lorlatinib showing pronounced central nervous system activities. Intracranial efficacy is an important feature for these agents, as metastatic lesions frequently occur in the central nervous system in the ALK-positive setting. Here, we report on an updated case of a patient who received her diagnosis in 2005 and has had disease progression with new lesions on six occasions over the last 8 years. During the first two progressions, only local recurrence was observed. After that, the lungs stayed clear and the patient progressed exclusively in the brain and spinal cord. Initial treatments consisted of chemotherapy and radiotherapy. In 2012, ALK-directed targeted therapy became available, and crizotinib was administered. The treatment was switched to brigatinib 3 years later be..... READ ARTICLE

Anti-Cancer Drugs
DOI:10.1097/CAD.0000000000000800

Authors: Hochmair, Maximiliana; Weinlinger, Christopha; Prosch, Helmut

20P - Detecting therapy-guiding aberrations in platelets and plasma at the transcriptome level in non-small-cell lung cancer

Background: The detection of driver aberrations such as EGFR and ALK, in tumour tissue or plasma has become important for treating lung cancer patients. The aim of this study is to explore the feasibility of detecting therapy-guiding aberrations in RNA, isolated from platelet and plasma samples. Conclusions: In conclusion, the fraction of tumour-derived RNA transcripts in plasma and platelets appears to be very low or undetectable. Our data indicates that plasma and platelet-derived RNA is not a good source to identify tumour cell specific genomic aberrations. READ ARTICLE

Annals of Oncology DOI:10.1093/annonc/mdz413.025

Authors: P. Meng, A. A. Rybczynska, J. Wei, M. M. Terpstra, W. Timens, E. Schuuring, T. J. N. Hiltermann, H. J. M. Groen, K. Kok, A. J. Van der Wekken, A. Van den Berg

Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial

Background: Ensartinib is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases. We aimed to assess the efficacy and safety of ensartinib in ALK-positive patients with non-small-cell lung cancer (NSCLC), in whom crizotinib therapy was unsuccessful. The associations between ensartinib efficacy and crizotinib-resistant mutations were also explored. Interpretation: Ensartinib has activity and is well tolerated in patients with crizotinib-refractory, ALK-positive NSCLC, including those with brain metastases. The role of ensartinib in patients in whom other second-generation ALK inhibitors have been unsuccessful warrants further studies. READ ARTICLE

The Lancet Respiratory Medicine DOI:10.1016/S2213-2600(19)30252-8

Authors: Yunpeng Yang, Jianya Zhou, Jianying Zhou, Jifeng Feng, Wu Zhuang, Prof Jianhua Chen, Jun Zhao, Wei Zhong, Yanqiu Zhao, Yiping Zhang, Yong Song, Yi Hu, Prof Zhuang Yu, Youling Gong, Yuan Chen, Feng Ye, Shucai Zhang, Lejie Cao, Yun Fan, Prof Gang Wu, Yubiao Guo, Chengzhi Zhou, Kewei Ma, Jian Fang, Weineng Feng, Prof Yunpeng Liu, Zhendong Zheng, Prof Gaofeng Li, Prof Ning Wu, Prof Wei Song, Xiaoqing Liu, Shijun Zhao, Lieming Ding, Prof Li Mao, Giovanni Selvaggi, Xiaobin Yuan, Yuanqing Fu, Tao Wang, Shanshan Xiao, Li Zhang

EP101-62 The Safety Profile and Preliminary Efficacy of Ceritinib 450mg with Food in Chinese ALK/ROS-1 Positive NSCLC Patients

Ceritinib have shown potent efficacy in both ALK and ROS-1 rearranged NSCLC. However, high rate of treatment interruption was suffered due to gastrointestinal or liver toxicity using Ceritinib 750mg fasting in previous study. Recently, ASCEND-8 study reported an improved tolerance and a trend to better efficacy with 450mg with food, but little data is available in Chinese patients. This first-time real-world study aims to assess the safety profile and preliminary efficacy of Ceritinib 450mg with food in Chinese patients. From Oct 2018 to March 2019, 51 ALK or ROS1 positive NSCLC patients received ceritinib were enrolled from 8 centers in Sichuan province. Safety profile and preliminary efficacy were retrospectively analyzed. The follow-up was to 31st March 2019. The study found Ceritinib 450mg with food demonstrated a good safety profile and efficacy with lower AE incidence rate and better compliance rate compare to ASCEND-8 data for Chinese patients in real-world setting...... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2035

Authors: Y. Tian, P. Yu, X. Yin, K. Wang, M. Huang, Y. Wang, Y. Gong, J. Li

Conference PaperKirk SmithOctober 1, 2019Ceritinib, non-small-cell lung cancer, Safety

Systematic review of sequencing of ALK inhibitors in ALK-positive non-small-cell lung cancer

The objective of this study was to understand outcomes of patients treated with ALK inhibitors, especially when ALK inhibitors are followed by other ALK inhibitors. A systematic literature review was conducted in PubMed, Embase, and Cochrane through July 17, 2017. Conference abstracts (three meetings in past 2 years) also were searched. Of 504 unique publications, 80 met inclusion criteria (47 clinical trials, 33 observational studies). Observational studies have the potential to provide information for ALK inhibitors used sequentially. Ten observational studies reported median overall survival of crizotinib-led sequences ranging from 30.3 to 63.75 months from initiation of crizotinib; 49.4-89.6 months from metastatic non-small-cell lung cancer diagnosis; and 15.5-22.0 months from initiation of the second-generation ALK inhibitor after initial crizotinib. Sequencing of ALK inhibitors may benefit patients progressing on initial ALK inhibitors. READ ARTICLE

Lung Cancer: Targets and Therapy DOI:10.2147/LCTT.S179349

Authors: Barrows SM, Wright K, Copley-Merriman C, Kaye JA, Chioda M, Wiltshire R, Torgersen KM, Masters ET.

Review PaperKirk SmithFebruary 8, 2019ALK, NSCLC, carcinoma, non-small-cell lung, non-small-cell lung cancer

Ceritinib for an anaplastic lymphoma kinase rearrangement-positive patient previously treated with alectinib with poor performance status

ALK inhibitors are promising for treating ALK rearrangement non-small-cell lung cancer (NSCLC), but secondary mutations of ALK can sometimes inhibit their effectiveness. A 54-year-old woman with lung adenocarcinoma harboring ALK rearrangement previously treated with first-line alectinib and second-line cisplatin/pemetrexed showed poor performance status (PS) with rapid progression. She was treated with ceritinib as salvage treatment, upon which tumor shrinkage was demonstrated on CT and her PS gradually improved. The best supportive care is recommended for patients with advanced NSCLC with poor PS due to lower treatment efficacy and more toxicities than those with good PS. In this case, rapid progression led to a poor PS; however, ceritinib achieved a breakthrough in this case. The optimal treatment sequence and key drugs in ALK-positive NSCLC remain controversial. READ ARTICLE

OncoTargets and Therapy DOI:10.2147/OTT.S186213

Authors: Rui Kitadai, Yusuke Okuma, and Shoko Kawai