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.

Brigatinib versus Crizotinib in Anaplastic Lymphoma Kinase (ALK) Inhibitor–Naive Advanced ALK-Positive Non–Small Cell Lung Cancer: Final Results of the Phase 3 ALTA-1L Trial

In the phase 3 ALTA-1L study of brigatinib in anaplastic lymphoma kinase (ALK) inhibitor–naive advanced ALK+ NSCLC, brigatinib demonstrated superior progression-free survival (PFS) versus crizotinib in 2 planned interim analyses. We report final efficacy, safety, and exploratory results. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.07.035

Authors: D. Ross Camidge, Hye Ryun Kim, Myung-Ju Ahn, James CH. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Maria Rosario Garcia Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander I. Spira, Scott N. Gettinger, Marcello Tiseo, Huamao M. Lin, Yuyin Liu, Florin Vranceanu, Huifeng Niu, Pingkuan Zhang, Sanjay Popat

ALK Inhibitors in ALK-positive NSCLC with Central Nervous System Metastases

In anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer, brain metastases occur in 22–33% of cases at diagnosis and could reach up to 70% after crizotinib failure. Next-generation ALK inhibitors (ngALKi) have superior intracranial activity and prolonged responses compared with crizotinib and chemotherapy, as was shown in treatment-naïve or crizotinib pre-treated patients, irrespective of prior brain irradiation. Nevertheless, central nervous system relapse is also seen with ngALKi. Tailored treatment is necessary to obtain long-term survival without detrimental effects on cognition. Possible options include profiling secondary mutations to select sequential ngALKi, stereotactic radiotherapy and/or surgery, with the aim to avoid/deter whole brain irradiation. READ ARTICLE

touchONCOLOGY DOI:10.17925/EOH.2020.16.1.18

Authors: Mihaela Aldea, Benjamin Besse, Lizza EL Hendriks

Efficacy and safety of ceritinib in anaplastic lymphoma kinase-rearranged non-small cell lung cancer: A systematic review and meta-analysis

What is known and objective: Ceritinib is a new, oral, potent and selective second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the Food and Drug Administration of the United States in April 2014. It is active in crizotinib-re-sistant patients, especially in patients with non-small cell lung cancer (NSCLC) and brain metastasis. The aim of this study was to analyse the effects and side effects of ceritinib in ALK-rearranged NSCLC.Methods: We searched articles published from January 1980 to March 2019 in PubMed, EMBASE, Cochrane Library and Web of Science. The pooled estimate and 95% CI were calculated with DerSimonian-Laird method and the random effect model.Results and discussion: From 15 articles, 2,598 patients were included in the meta-analysis. Eleven studies reported the ORR, and the DCR was presented in 10 stud-ies. The ORR and DCR of ceritinib were 0.48 (95% CI, 0.39-0.57) and 0.76 (95% CI, 0.69-0.82), respectively. The PFS and OS were presented in nine and ..... READ ARTICLE

Journal of Clinical Pharmacy and Therapeutics DOI:10.1111/jcpt.13157

Authors: Wei Tian, Ping Zhang, Yuan Yuan, Xiao-Hui Deng, Rui Yue, Xiao-Zhu Ge

Imaging Features and Metastatic Patterns of Advanced ALK-Rearranged Non–Small Cell Lung Cancer

"ALK rearrangements are an established targetable oncogenic driver in non–small cell lung cancer (NSCLC). The goal of this study was to determine the imaging features of the primary tumor and metastatic patterns in advanced ALK-rearranged (ALK+) NSCLC that may be different from those in EGFR-mutant (EGFR+) or EGFR/ALK wild-type (EGFR−/ALK−) NSCLC. CONCLUSION. Advanced ALK+ NSCLC has primary tumor imaging features and patterns of metastasis that are different from those of EGFR+ or EGFR−/ALK− wild type NSCLC at the time of initial presentation. READ ARTICLE

American Journal of Roentgenology DOI:10.2214/AJR.19.21982

Authors: Dexter P. Mendoza, Jessica J. Lin, Marguerite M. Rooney, Tianqi Chen, Lecia V. Sequist, Alice T. Shaw, Subba R. Digumarthy"

Real-World OutcomesKirk SmithApril 1, 2020ALK, anaplastic lymphoma kinase, lung cancer, metastasis

ALK Rearrangement Adenocarcinoma with Histological Transformation to Squamous Cell Carcinoma Resistant to Alectinib and Ceritinib

Specific tyrosine-kinase inhibitors (TKIs) are widely used for the treatment of non-small-cell lung cancers with anaplastic lymphoma kinase (ALK) translocations. However, most treated patients eventually develop resistance to the TKIs. The histological transformation into small cell carcinoma is well known to be the underlying mechanism for acquired resistance; however, transformation to squamous cell carcinoma is extremely rare. We, herein, report a case of ALK rearrangement-positive adenocarcinoma that transformed to squamous cell carcinoma after administration of alectinib, and was found to be resistant to ceritinib. READ ARTICLE

OncoTargets and therapy DOI:10.2147/OTT.S236706

Authors: Kaiho T, Nakajima T, Iwasawa S, Yonemori Y, Yoshino I.

Clinicopathological and Prognostic Significance of EML4-ALK Rearrangement in Patients with Surgically Resected Lung Adenocarcinoma: A Propensity Score Matching Study

Objective The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is a key oncogenic driver in non-small cell lung cancer (NSCLC). This study analyzed the clinicopathological characteristics and prognostic significance of EML4-ALK fusion gene in patients with surgically resected adenocarcinoma. Methods The clinicopathological characteristics of 1056 consecutive patients with surgically resected stage I–IIIA adenocarcinoma were collected from February 2014 to October 2014, and EML4-ALK rearrangement was detected using real-time polymerase chain reaction (RT-PCR) technology. To compare the imaging and pathological features, a propensity score matching (PSM) method was performed. The follow-up information was collected to evaluate the long-term outcomes of patients with EML4-ALK rearrangement. Results The prevalence of EML4-ALK rearrangement was 6.6% in 1056 consecutive patients. A total of 70 EML4-ALK-positive and 210 EML4-ALK-negative patie..... READ ARTICLE

Cancer management and research DOI:10.2147/CMAR.S229217

Authors: Shi J, Gu W, Zhao Y, Zhu J, Jiang G, Bao M, Shi J.

Anaplastic lymphoma kinase inhibitor related pneumonitis in patients with non-small cell lung cancer

Anaplastic lymphoma kinase (ALK) inhibitor-related pneumonitis (ALK-IIP) is relatively rare but sometimes fatal, so the timely diagnosis of ALK-IIP is important for enabling prompt management. However, the detailed radiologic characteristics and clinical course of ALK-IIP are still unclear. This study was performed to investigate the clinical and radiologic characteristics and risk factors of ALK-IIP in patients with non-small cell lung cancer (NSCLC).

A total of 250 NSCLC patients who had been treated with ALK inhibitors were retrospectively enrolled. Chest computed tomography (CT) was classified into 4 CT patterns using the 2013 guideline for idiopathic interstitial pneumonia: cryptogenic organizing pneumonia (COP), hypersensitivity pneumonitis (HP), acute interstitial pneumonia (AIP), and nonspecific interstitial pneumonia. Clinical characteristics including toxicity grading and treatment course were analyzed in regarding to CT patterns. Clinical characteristics were compared betwe..... READ ARTICLE

Medicine DOI:10.1097/MD.0000000000018131

Authors: Hwang Hye Jeon, Kim Mi Young, Choi Chang-Min, Lee Jae Cheol

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