Lung Cancer: Targets and Therapy最新文献

{"title":"Incidence of <i>ROS1</i>-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients.","authors":"Anurag Mehta, Mumtaz Saifi, Ullas Batra, M Suryavanshi, Kush Gupta","doi":"10.2147/LCTT.S244366","DOIUrl":"10.2147/LCTT.S244366","url":null,"abstract":"<p><strong>Background: </strong>The <i>ROS1</i> gene is a member of the \"sevenless\" subfamily of tyrosine-kinase insulin-receptor genes. <i>ROS1</i>-fusion rearrangement causes constitutive downstream signal transduction, with an oncogenic role in non-small-cell lung carcinoma (NSCLC). Fortunately, crizotinib, an ALK1 tyrosine-kinase inhibitor, provides long-term disease control. The objective of this molecular epidemiological study was to estimate the frequency of <i>ROS1</i> rearrangements and evaluate treatment outcomes with crizotinib therapy.</p><p><strong>Methods: </strong>Patients with stage IV NSCLC adenocarcinoma histology were considered for this study. The study was conducted according to the ethical principles stated in the latest version of the Declaration of Helsinki and the applicable guidelines for good clinical practice. Clinical characteristics and treatment details were collected from patients' medical records.</p><p><strong>Results: </strong>A total of 709 stage IV NSCLC adenocarcinoma patients were included in the study. There were 457 (64.46%) men and 252 (35.54%) women, with a median age of 60 years. <i>ROS1</i>-gene rearrangement was positive in 20 (2.82%) cases, 13 using Fluorescent In-Situ Hybridization (FISH), and two and five cases, respectively, using immunohistochemistry (IHC) and next-generation sequencing (NGS), followed by confirmation with FISH. Fourteen of the 20 patients with <i>ROS1</i>-gene rearrangement received crizotinib therapy, with an objective response rate of 64.28%. At a median follow-up of 6 months, the study had not achieved the end points of median progression free survival and overall survival.</p><p><strong>Conclusion: </strong><i>ROS1</i>-gene rearrangement was present at a relatively higher frequency of 2.8% in north Indian patients with lung adenocarcinoma and was successfully targeted by crizotinib therapy. Although the only US Food and Drug Administration and Conformité Européenne approved method for testing <i>ROS1</i> rearrangement is NGS, FISH alone or IHC with D4D6 antibody as initial screen with subsequent confirmation of IHC-positive cases by FISH are cost-effective methods in institutions lacking NGS facilities.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/97/lctt-11-19.PMC7047993.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37726303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in <i>ALK</i>-Rearranged NSCLC: A Report of Two Cases.","authors":"Viola W Zhu,&nbsp;Misako Nagasaka,&nbsp;Takafumi Kubota,&nbsp;Kunil Raval,&nbsp;Natasha Robinette,&nbsp;Octavio Armas,&nbsp;Wajd Al-Holou,&nbsp;Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S224991","DOIUrl":"https://doi.org/10.2147/LCTT.S224991","url":null,"abstract":"<p><p>Central nervous system (CNS) metastasis carries a significant morbidity and mortality in anaplastic lymphoma kinase (<i>ALK</i>)-rearranged non-small cell lung cancer (NSCLC). Next-generation ALK tyrosine kinase inhibitors (TKIs) are highly CNS-penetrant and have demonstrated remarkable intracranial activity across clinical studies, and yet radiation remains the mainstay of treatment modality against CNS metastasis. We have previously reported alectinib can induce CNS radiation necrosis even after a remote history of radiation (7 years post-radiation). Lorlatinib is another potent next-generation ALK TKI that can overcome many <i>ALK</i> resistance mutations and has been shown to have excellent activity in patients with baseline CNS metastasis. Here we report two <i>ALK</i>-rearranged NSCLC patients who developed radiation necrosis shortly after initiating lorlatinib following progression on the sequential treatment of crizotinib, alectinib, and brigatinib. In both cases, radiation necrosis is evidenced by serial MRI images and histological examination of the resected CNS metastasis that had previously been radiated. Our cases highlight the importance of recognizing CNS radiation necrosis that may mimic disease progression in <i>ALK</i>-rearranged NSCLC treated with and potentially precipated by next-generation ALK TKIs.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S224991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37612439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer.","authors":"Yuen Yee Cheng, Emma M Rath, Anthony Linton, Man Lee Yuen, Ken Takahashi, Kenneth Lee","doi":"10.2147/LCTT.S186843","DOIUrl":"10.2147/LCTT.S186843","url":null,"abstract":"<p><p>Asbestos is a naturally occurring mineral consisting of extremely fine fibres that can become trapped in the lungs after inhalation. Occupational and environmental exposures to asbestos are linked to development of lung cancer and malignant mesothelioma, a cancer of the lining surrounding the lung. This review discusses the factors that are making asbestos-induced lung cancer a continuing problem, including the extensive historic use of asbestos and decades long latency between exposure and disease development. Genomic mutations of DNA nucleotides and gene rearrangements driving lung cancer are well-studied, with biomarkers and targeted therapies already in clinical use for some of these mutations. The genes involved in these mutation biomarkers and targeted therapies are also involved in epigenetic mechanisms and are discussed in this review as it is hoped that identification of epigenetic aberrations in these genes will enable the same gene biomarkers and targeted therapies to be used. Currently, understanding of how asbestos fibres trapped in the lungs leads to epigenetic changes and lung cancer is incomplete. It has been shown that oxidoreduction reactions on fibre surfaces generate reactive oxygen species (ROS) which in turn damage DNA, leading to genetic and epigenetic alterations that reduce the activity of tumour suppressor genes. Epigenetic DNA methylation changes associated with lung cancer are summarised in this review, and some of these changes will be due to asbestos exposure. So far, little research has been carried out to separate the asbestos driven epigenetic changes from those due to non-asbestos causes of lung cancer. Asbestos-associated lung cancers exhibit less methylation variability than lung cancers in general, and in a large proportion of samples variability has been found to be restricted to promoter regions. Epigenetic aberrations in cancer are proving to be promising biomarkers for diagnosing cancers. It is hoped that further understanding of epigenetic changes in lung cancer can result in useful asbestos-associated lung cancer biomarkers to guide treatment. Research is ongoing into the detection of lung cancer epigenetic alterations using non-invasive samples of blood and sputum. These efforts hold the promise of non-invasive cancer diagnosis in the future. Efforts to reverse epigenetic aberrations in lung cancer by epigenetic therapies are ongoing but have not yet yielded success.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/d3/lctt-11-1.PMC6955579.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37611377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibitors for the Treatment of Unresectable Stage III Non-Small Cell Lung Cancer: Emerging Mechanisms and Perspectives.","authors":"Hiroyuki Inoue,&nbsp;Isamu Okamoto","doi":"10.2147/LCTT.S184380","DOIUrl":"https://doi.org/10.2147/LCTT.S184380","url":null,"abstract":"<p><p>There has been no improvement in outcome for patients with unresectable locally advanced (stage III) non-small cell lung cancer (NSCLC) for more than 10 years. The standard treatment for these patients is definitive concurrent chemotherapy and radiation (CCRT). Although the goal of treatment in this setting is to achieve a cure, most patients progress and their prognosis is poor, with a 5-year survival rate of 15-30%. There is thus an urgent need for the development of novel anticancer treatments in this patient population. Recent advances in cancer immunotherapy have led to a marked improvement in clinical outcome for advanced NSCLC. Such immunotherapy mainly consists of the administration of immune checkpoint inhibitors (ICIs) such as antibodies to cytotoxic T lymphocyte-associated protein-4 (CTLA-4) or to either programmed cell death-1 (PD-1) or its ligand PD-L1. Durvalumab (MEDI4736) is a high-affinity human immunoglobulin G1 monoclonal antibody that blocks the binding of PD-L1 on tumor cells or antigen-presenting cells to PD-1 on T cells. The PACIFIC study recently evaluated consolidation immunotherapy with durvalumab versus placebo administered after concurrent chemoradiotherapy (CCRT) in patients with unresectable stage III NSCLC. It revealed a significant improvement in both progression-free and overall survival with durvalumab, and this improvement was associated with a favorable safety profile. This achievement has made durvalumab a standard of care for consolidation after CCRT in patients with unresectable stage III NSCLC, and it has now been approved in this setting by regulatory agencies in the United States, Canada, Japan, Australia, Switzerland, Malaysia, Singapore, India, and the United Arab Emirates. In this review, we briefly summarize the results of the PACIFIC trial, including those of post hoc analysis, and we address possible molecular mechanisms, perspectives, and remaining questions related to combined treatment with CCRT and ICIs in this patient population.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S184380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37677185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes Following Stereotactic Body Radiotherapy with Intensity-Modulated Therapy versus Three-Dimensional Conformal Radiotherapy in Early Stage Non-Small Cell Lung Cancer.","authors":"Michael Mix,&nbsp;Sean Tanny,&nbsp;Tamara Nsouli,&nbsp;Ryan Alden,&nbsp;Rishabh Chaudhari,&nbsp;Russell Kincaid,&nbsp;Paula F Rosenbaum,&nbsp;Jeffrey A Bogart,&nbsp;Paul Aridgides","doi":"10.2147/LCTT.S235713","DOIUrl":"https://doi.org/10.2147/LCTT.S235713","url":null,"abstract":"<p><strong>Introduction: </strong>The treatment techniques used for stereotactic body radiation therapy (SBRT) for early-stage lung cancer continue to evolve. In this study, clinical outcomes following SBRT were evaluated according to the use of either 3D conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT).</p><p><strong>Patients and methods: </strong>Patients with stage I NSCLC who received SBRT from 2007 to 2015 were retrospectively reviewed. Disease control and survival were assessed using Kaplan-Meier estimates. Dosimetric analyses for target dose heterogeneity and coverage were performed.</p><p><strong>Results: </strong>A total of 297 patients with 351 lesions were included. 3DCRT was used in 52% and IMRT in 48%. IMRT was utilized at a higher rate in more recent years. The most common regimens were 48 Gy in 4 fractions and 54-60 Gy in 3 fractions. With a median follow up of 22.7 months, there were 17 local failures for a crude relapse rate of 5.7%. Local failure did not differ in patients treated with 3DCRT and IMRT (4.9% vs 6.5%, p=0.573). Mean dose to gross tumor volume (GTV) as a percent of prescription dose was higher with 3DCRT compared with IMRT (107.7% vs 103.6%, p < 0.0001). Tumor stage, histology, and SBRT regimen did not correlate with local tumor control. Overall survival for the entire population approximated 72% at 2 years. Treatment was well tolerated with 6 documented grade 3+ events.</p><p><strong>Conclusion: </strong>In this single-institution cohort of SBRT for early-stage NSCLC, there was no discernible difference in clinical outcomes between those treated with 3DCRT and IMRT.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S235713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37518232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma.","authors":"Chiara Baldovini,&nbsp;Giulio Rossi,&nbsp;Alessia Ciarrocchi","doi":"10.2147/LCTT.S186779","DOIUrl":"https://doi.org/10.2147/LCTT.S186779","url":null,"abstract":"<p><p>Pulmonary sarcomatoid carcinoma (PSC) is a heterogeneous category of primary lung cancer accounting from 0.3% to 3% of all primary lung malignancies. According to the most recent 2015 World Health Organization (WHO) classification, PSC includes several different variants of malignant epithelial tumors (carcinomas) histologically mimicking sarcomas showing or entirely lacking a conventional component of non-small cell lung cancer (NSCLC). Thus, this rare subheading of lung neoplasms includes pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, pulmonary blastoma, and carcinosarcoma. A diagnosis of PSC may be suspected on small biopsy or cytology, but commonly requires a surgical resection to reach a conclusive definition. The majority of patients with PSC consists of elderly, smoking men with a large, peripheral mass characterized by well-defined margins. However, presentation with a central, polypoid endobronchial lesion is well-documented, particularly in pleomorphic carcinoma and carcinosarcoma showing a squamous cell carcinoma component. As expected, PSC may pose diagnostic problems and immunohistochemistry is largely used when pathologists deal these tumors in routine practice. Indeed, PSC tends to overexpress molecules associated with the epithelial-to-mesenchymal transition, such as vimentin, but the panel of immunostains also includes epithelial markers (cytokeratins, EMA), TTF-1, p40 and negative markers (e.g., melanocytic, mesothelial and sarcoma-related primary antibodies). Although rare, PSC has increased their interest among oncologist community for different reasons: a. identification of the epithelial-to-mesenchymal phenomenon as a major mechanism of secondary resistance to tyrosine kinase inhibitors; b. over-expression of PD-L1 and effective treatment with immunotherapy; c. identification of <i>c-MET</i> exon 14 skipping mutation representing an effective target to crizotinib and other specific inhibitors. In this review, the feasibility of the diagnosis of PSC, its differential diagnosis and novel molecular findings characterizing this group of lung tumor are discussed.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S186779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37446465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time To Response In Patients With Advanced Anaplastic Lymphoma Kinase (<i>ALK</i>)-Positive Non-Small-Cell Lung Cancer (NSCLC) Receiving Alectinib In The Phase II NP28673 And NP28761 Studies.","authors":"Shirish Gadgeel, Alice T Shaw, Fabrice Barlesi, Lucio Crino, James Ch Yang, Anne-Marie Dingemans, Dong-Wan Kim, Filippo de Marinis, Mathias Schulz, Shiyao Liu, Ravindra Gupta, Vlatka Smoljanovic, Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S209231","DOIUrl":"10.2147/LCTT.S209231","url":null,"abstract":"<p><strong>Introduction: </strong>Alectinib is a highly selective and potent ALK inhibitor, approved for the treatment of patients with metastatic <i>ALK</i>+ NSCLC based on results from the Phase II global NP28673 (NCT01801111) and North American NP28761 (NCT01871805) studies.</p><p><strong>Methods: </strong>This exploratory analysis of two Phase II studies of alectinib (NP28673/NP28761) investigated time to systemic response (TTR) and time to central nervous system (CNS) response (TTCR) in patients with previously treated advanced anaplastic lymphoma kinase fusion gene-positive (<i>ALK</i>+) non-small-cell lung cancer. Patients (n=225) received 600 mg oral alectinib twice daily and had scans every 6/8 weeks (NP28673/NP28761).</p><p><strong>Results: </strong>For NP28673 and NP28761, respectively: median follow-up was 21.3 months/17.0 months; most responders (72.6%/82.9%) responded by the first disease assessment; median TTR was 8 weeks (95% confidence interval [CI]: 8.00-8.14)/6 weeks (95% CI: 5.86-6.14); median TTCR in responders with measurable baseline CNS disease was 8 weeks (95% CI: 7.86-10.29)/6 weeks (95% CI: 5.71-not evaluable). Similar results were observed regardless of measurable/non-measurable disease.</p><p><strong>Discussion: </strong>These data suggest that alectinib achieves a rapid response in patients, both systemically and in the CNS.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/2a/lctt-10-125.PMC6859466.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37602775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Landscape on CT screening for lung cancer in Asia.","authors":"Natthaya Triphuridet,&nbsp;Claudia Henschke","doi":"10.2147/LCTT.S192643","DOIUrl":"https://doi.org/10.2147/LCTT.S192643","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer incidence and mortality worldwide. Approximately 60% of the world's new cases of lung cancer and deaths from it are expected in Asia in 2018. Currently, lung cancer screening using low-dose computed tomography (LDCT) is recommended for heavy smokers in North America, Europe and some countries in Asia. Tobacco smoking being the major risk factor for lung cancer, but in Asia, lung cancer in never-smokers (LCINS) is also a concern. This paper reviews on lung cancer incidence, mortality, etiology, smoking in Asia, and systematic reviews on LDCT lung cancer screening studies, including ongoing projects and recommendation on lung cancer screening in Asia. Some of the earliest studies of LDCT lung cancer screening worldwide were in Asia. Many countries in Asia have developed LDCT screening studies in various high-risk participants. Currently, there are several ongoing large-scale lung cancer screening trials to evaluate the efficacy of LDCT screening for never-smokers and light smokers, as well as heavy smokers, and to evaluate the feasibility of population-based LDCT lung cancer screening.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S192643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective study evaluating the pretreatment tumor volume (PTV) in non-small cell lung cancer (NSCLC) as a predictor of response to program death-1 (PD-1) inhibitors","authors":"M. Nagasaka, Nadine H Abdallah, Marcus Crosby, Nithin Thummala, Dhaval Patel, A. Wozniak, S. Gadgeel, J. Abrams, A. Sukari","doi":"10.2147/LCTT.S219886","DOIUrl":"https://doi.org/10.2147/LCTT.S219886","url":null,"abstract":"Introduction of hypothesis Little information is available regarding the imaging characteristics that assist in differentiating responders from non-responders. We hypothesized that patients with higher pretreatment tumor volume (PTV) would have lower response rates and shorter overall survival (OS). Methods Data from patients who received at least one dose of program death-1 (PD-1) inhibitors before August 31, 2016 were captured from our institution’s pharmacy database. The primary objective was to determine the association of PTV with best response, evaluated utilizing RECIST v1.1 criteria. Secondary objectives were estimation of progression-free survival (PFS) and OS. PTV was measured using the Philips Intellispace Multi-Modality Tumor Tracking application. Results 116 non-small cell lung cancer (NSCLC) patients were evaluated. 66% patients had adenocarcinoma, 28% had squamous cell carcinoma and 5% had poorly differentiated NSCLC. Median PTV was 53.7 cm3 (95% CI: 13.3–107.9). Only one individual had no metastases and the remainder had M1 disease; 38% M1a, 10% M1b, 51% M1c. Most (79%) were previously treated. There were no complete responses; among those followed for at least 6 weeks, 26% had a partial response, 39% stable disease and 34% PD; 4% had no recorded response. There were no strong associations of PTV with any of the demographic or clinical characteristics. There was no association between PTV and OS (HR 1.2, P=0.26) or PFS (HR 1.1, P=0.47). Liver metastasis was associated with shorter survival (HR=2.8, P=0.05). Conclusion PTV in NSCLC did not prove to be a predictor of response to PD-1 inhibitors but having liver metastasis was associated with significantly shorter survival.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87017111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profile of entrectinib and its potential in the treatment of ROS1-positive NSCLC: evidence to date.","authors":"Francesco Facchinetti,&nbsp;Luc Friboulet","doi":"10.2147/LCTT.S190786","DOIUrl":"https://doi.org/10.2147/LCTT.S190786","url":null,"abstract":"<p><p>ROS1 inhibition provides impressive survival benefits in <i>ROS1</i>-rearranged non-small cell lung cancer (NSCLC) patients. Crizotinib is the only tyrosine kinase inhibitor (TKI) approved by both FDA and EMA for the treatment of ROS1-positive lung cancer. In addition, several TKI have been tested with preliminary proofs of success in this oncogene-driven disease, either in the post-crizotinib setting or as first-line targeted agents. Here we present the evidence concerning entrectinib, an ALK/ROS1/NTRK inhibitor developed across different tumor types harboring rearrangements in these genes, in the context of ROS1-driven NSCLC. Of interest, in August 2019 entrectinib was granted by FDA accelerated approval for the treatment of <i>ROS1</i>-rearranged NSCLC, as well as of NTRK-driven solid tumors.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S190786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}