Lung Cancer: Targets and Therapy最新文献

{"title":"Differential response to a combination of full-dose osimertinib and crizotinib in a patient with <i>EGFR</i>-mutant non-small cell lung cancer and emergent <i>MET</i> amplification.","authors":"Viola W Zhu,&nbsp;Alexa B Schrock,&nbsp;Siraj M Ali,&nbsp;Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S190403","DOIUrl":"https://doi.org/10.2147/LCTT.S190403","url":null,"abstract":"<p><p>Exploring resistance mechanisms in patients with <i>EGFR</i>-mutant non-small-cell lung cancer (NSCLC) upon disease progression on EGFR tyrosine kinase inhibitors (TKIs) has been an area of great interest as it may lead to effective next-line treatment strategies. Here we report a case of emergent <i>MET</i> amplification detected in a tumor sample from a patient with NSCLC harboring EGFR L858R mutation after disease progression on erlotinib. The patient subsequently had a sustained partial response to a combination of full-dose osimertinib and crizotinib with excellent tolerance but eventually had central nervous system (CNS) progression. Comprehensive genomic profiling performed on the resected brain sample continued to demonstrate <i>MET</i> amplification as an acquired resistance mechanism. A review of literature shows several groups have utilized similar combination regimens (erlotinib or osimertinib + crizotinib or cabozantinib), albeit with various dosing to target <i>MET</i> alterations in patients with <i>EGFR</i>-mutant NSCLC. As more actionable resistance mechanisms are identified, we envision combination TKI therapy will be readily adopted in clinical practice. Our case report adds to a growing body of evidence that combination osimertinib and crizotinib should be recommended to <i>EGFR</i>-mutant NSCLC patients with emergent <i>MET</i> amplification as acquired resistance. More importantly, as crizotinib has limited brain penetration, developing next-generation MET inhibitors with better CNS activity is urgently needed.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"10 ","pages":"21-26"},"PeriodicalIF":3.6,"publicationDate":"2019-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S190403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37064771","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":"Outcome of uncommon EGFR mutation positive newly diagnosed advanced non-small cell lung cancer patients: a single center retrospective analysis.","authors":"Shruti Kate,&nbsp;Anuradha Chougule,&nbsp;Amit Joshi,&nbsp;Vanita Noronha,&nbsp;Vijay Patil,&nbsp;Rohit Dusane,&nbsp;Leena Solanki,&nbsp;Priyanka Tiwrekar,&nbsp;Vaishakhi Trivedi,&nbsp;Kumar Prabhash","doi":"10.2147/LCTT.S181406","DOIUrl":"https://doi.org/10.2147/LCTT.S181406","url":null,"abstract":"<p><strong>Background: </strong>The significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients.</p><p><strong>Patients and methods: </strong>We retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records. Survival plot was calculated using Kaplan-Meier method and compared between groups using log-rank test.</p><p><strong>Results: </strong>Out of 1,260 EGFR mutation-positive patients, 83 (6.58%) had uncommon mutations in isolation or in various combinations. Uncommon mutations were more frequent in men, never-smokers, and adenocarcinomas. Overall, exon 18 G719X, exon 20 insertion, exon 20 T790M, exon 20 S768I, and exon 21 (L858R/L861Q) were present in 9.6%, 19.3%, 12%, 3.6%, and 3.6% patients, respectively. Dual mutation positivity was found in 50.6% patients. On classifying patients as per tyrosine kinase inhibitor (TKI) sensitivity, it was found that majority of the patients had a combination TKI sensitive and insensitive mutations. The median duration of follow-up was 13 months. Five patients were lost to follow-up. Median progression-free survival on first line therapy was 6.7 months (95% CI: 4.8-8.5). Median overall survival (OS) of patients who received TKI during the course of their disease was 20.2 months (95% CI: 11.4-28.9). Median overall survival (mOS) of the entire cohort was 15.8 months (95% CI: 10.1-21.5). Among all uncommon mutations, patients with dual mutations did better, with an mOS time of 22.6 months (95% CI: 8.2-37.0, <i>P</i>=0.005). It was observed that TKI sensitive/TKI insensitive dual mutations had a superior OS of 28.2 months (95% CI: 15.2-41.2, <i>P</i>=0.039) as compared to TKI sensitive and TKI insensitive EGFR mutations.</p><p><strong>Conclusion: </strong>Uncommon EGFR mutations constitute a heterogeneous group, hence, it is imperative to understand each subgroup more to define optimal treatment.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"10 ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2019-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S181406","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36975570","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":"Clinical outcomes following advanced respiratory motion management (respiratory gating or dynamic tumor tracking) with stereotactic body radiation therapy for stage I non-small-cell lung cancer.","authors":"Paul Aridgides,&nbsp;Tamara Nsouli,&nbsp;Rishabh Chaudhari,&nbsp;Russell Kincaid,&nbsp;Paula F Rosenbaum,&nbsp;Sean Tanny,&nbsp;Michael Mix,&nbsp;Jeffrey Bogart","doi":"10.2147/LCTT.S175168","DOIUrl":"https://doi.org/10.2147/LCTT.S175168","url":null,"abstract":"<p><strong>Purpose: </strong>To report the outcomes of stereotactic body radiation therapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) according to respiratory motion management method.</p><p><strong>Methods: </strong>Patients with stage I NSCLC who received SBRT from 2007 to 2015 were reviewed. Computed tomography (CT) simulation with four-dimensional CT was performed for respiratory motion assessment. Tumor motion >1 cm in the craniocaudal direction was selectively treated with advanced respiratory management: either respiratory gating to a pre-specified portion of the respiratory cycle or dynamic tracking of an implanted fiducial marker. Comparisons were made with internal target volume approach, which treated all phases of respiratory motion.</p><p><strong>Results: </strong>Of 297 patients treated with SBRT at our institution, 51 underwent advanced respiratory management (48 with respiratory gating and three with tumor tracking) and 246 underwent all-phase treatment. Groups were similarly balanced with regard to mean age (<i>P</i>=0.242), tumor size (<i>P</i>=0.315), and histology (<i>P</i>=0.715). Tumor location in the lower lung lobes, as compared to middle or upper lobes, was more common in those treated with advanced respiratory management (78.4%) compared to all-phase treatment (25.6%, <i>P</i><.0001). There were 17 local recurrences in the treated lesions. Kaplan-Meier analyses showed that there were no differences with regard to mean time to local failure (91.5 vs 98.8 months, <i>P</i>=0.56), mean time to any failure (73.2 vs 78.7 months, <i>P</i>=0.73), or median overall survival (43.3 vs 45.5 months, <i>P</i>=0.56) between patients who underwent advanced respiratory motion management and all-phase treatment.</p><p><strong>Conclusion: </strong>SBRT with advanced respiratory management (the majority with respiratory gating) showed similar efficacy to all-phase treatment approach for stage I NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"103-110"},"PeriodicalIF":3.6,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S175168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36707193","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":"Silicosis and lung cancer: current perspectives.","authors":"Takashi Sato,&nbsp;Takeshi Shimosato,&nbsp;Dennis M Klinman","doi":"10.2147/LCTT.S156376","DOIUrl":"https://doi.org/10.2147/LCTT.S156376","url":null,"abstract":"<p><p>\"Silica\" refers to crystalline particles formed by the combination of silicon with oxygen. Inhalation of silica particles promotes the development of pulmonary fibrosis that over prolonged periods increases the risk of lung cancer. The International Agency for Research on Cancer (IARC) classified crystalline silica as a human carcinogen in 1997. This categorization was questioned due to 1) the absence of dose-response findings, 2) the presence of confounding variables that complicated interpretation of the data and 3) potential selection bias for compensated silicosis. Yet, recent epidemiologic studies strongly support the conclusion that silica exposure increases the risk of lung cancer in humans independent of confounding factors including cigarette smoke. Based on this evidence, the US Occupational Safety and Health Administration (OSHA) lowered the occupational exposure limit for crystalline silica from 0.1 to 0.05 mg/m³ in 2013. Further supporting the human epidemiologic data, murine models show that chronic silicosis is associated with an increased risk of lung cancer. In animals, the initial inflammation induced by silica exposure is followed by the development of an immunosuppressive microenvironment that supports the growth of lung tumors. This work will review our current knowledge of silica-associated lung cancers, highlighting how recent mechanistic insights support the use of cutting-edge approaches to diagnose and treat silica-related lung cancer.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"91-101"},"PeriodicalIF":3.6,"publicationDate":"2018-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S156376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36737239","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":"Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation.","authors":"Nadine Abdallah,&nbsp;Misako Nagasaka,&nbsp;Eman Abdulfatah,&nbsp;Dongping Shi,&nbsp;Antoinette J Wozniak,&nbsp;Ammar Sukari","doi":"10.2147/LCTT.S173724","DOIUrl":"https://doi.org/10.2147/LCTT.S173724","url":null,"abstract":"<p><strong>Introduction: </strong>Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a well-recognized mechanism of resistance in <i>EGFR</i>-mutant adenocarcinoma upon treatment with TKIs, but rarely reported with programmed death1 (PD-1) inhibitors. We report two cases of potential transformation during treatment with PD-1 inhibitors.</p><p><strong>Case presentations: </strong>Case 1, a 65-year-old man was diagnosed with stage IVa lung adenocarcinoma on pleural fluid cytology. He received six cycles of carboplatin and pemetrexed, then maintained on pemetrexed. He had disease progression after nine cycles of pemetrexed and was switched to nivolumab. He progressed after five cycles of nivolumab. Core biopsy of the lung mass revealed SCLC. Case 2, a 68-year-old man was diagnosed with two primary NSCLCs and underwent resection. He had recurrence after several months and was treated with four cycles of carboplatin, paclitaxel, and pembrolizumab on clinical trial, with partial response. He was continued on pembrolizumab and had disease progression after 30 cycles. Biopsy of the new lesions showed SCLC.</p><p><strong>Discussion: </strong>Histologic transformation from NSCLC to SCLC can be explained by the presence of a common cell precursor. Proposed molecular mechanisms include loss of <i>RB1</i>, <i>TP53</i> mutations, and <i>MYC</i> amplification. The distinction between transformation and mixed histology tumors is challenging, especially when pathologic material used for the initial diagnosis is limited. The possibility of a second metachronous primary lung cancer cannot be excluded in our cases.</p><p><strong>Conclusion: </strong>Histologic transformation with PD-1 inhibitors could be under-recognized. Disease progression should prompt re-biopsy to uncover new histology and change in treatment. Future studies are needed to elucidate mechanisms and predictors of transformation.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"85-90"},"PeriodicalIF":3.6,"publicationDate":"2018-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S173724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36737238","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":"Amifostine- and chemoradiotherapy-related esophagitis in small cell lung cancer: a single institutional series and literature update.","authors":"Ariel E Pollock,&nbsp;Lowell Shinn,&nbsp;Richard Anderson,&nbsp;Sarah Butler,&nbsp;Jondavid Pollock","doi":"10.2147/LCTT.S155315","DOIUrl":"https://doi.org/10.2147/LCTT.S155315","url":null,"abstract":"<p><strong>Objectives: </strong>Concurrent chemoradiotherapy is considered a standard option for patients with stage 3 small cell lung carcinoma. A 25% risk of acute esophagitis is experienced by patients as a result of the volume of esophagus encompassed within a conformal radiotherapy technique. We reviewed our institutional experience administering the radioprotectant amifostine prior to daily radiotherapy to determine its effects on the onset of esophagitis.</p><p><strong>Materials and methods: </strong>From 2005 to 2016, 49 patients diagnosed with stage 3 small cell lung carcinoma received concurrent chemoradiotherapy. Chemotherapy (CT) consisted of cisplatin and etoposide with radiotherapy (RT) encompassing CT-identified gross tumor volume. In 32 patients (group 1), amifostine was delivered (500 mg subcutaneously divided in two injections) prior to the second daily RT fraction. The remaining 17 patients (group 2) did not receive amifostine due to choice or drug intolerance.</p><p><strong>Results: </strong>Metrics of esophagitis included weight loss and opiate requirement during treatment. About 31% of group 1 required opiates at a median RT dose of 3300 cGy, and 41% of group 2 required opiates at a median dose of 2250 cGy. The dose of radiotherapy delivered to 50% of the esophageal volume for group 1 was significantly greater than that in group 2 (3000 cGy vs 576 cGy).</p><p><strong>Conclusion: </strong>In this modern retrospective series of thoracic chemoradiotherapy in the treatment of stage 3 small cell lung cancer, amifostine that was delivered subcutaneously postponed the onset of esophagitis.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"79-84"},"PeriodicalIF":3.6,"publicationDate":"2018-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S155315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36511861","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":"Hypersensitivity in ALK-positive lung cancers exposed to ALK inhibitors: a case of successful switch to an alternative ALK inhibitor and systematic review of the literature.","authors":"Lei Deng,&nbsp;Janaki Sharma,&nbsp;Elizabeth Ravera,&nbsp;Balazs Halmos,&nbsp;Haiying Cheng","doi":"10.2147/LCTT.S173948","DOIUrl":"https://doi.org/10.2147/LCTT.S173948","url":null,"abstract":"<p><p>Alectinib can cause rare, but severe hypersensitivity. The cross-reactivity between different ALK inhibitors is unknown and desensitization is the only reported management. We hereby report the first case of severe delayed hypersensitivity developed in a lung cancer patient treated by alectinib, who was successfully managed by switching to brigatinib, another ALK inhibitor. The patient achieved excellent anti-tumor response to brigatinib. Our case provides an alternative and safe strategy in patients with alectinib-related hypersensitivity.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"73-77"},"PeriodicalIF":3.6,"publicationDate":"2018-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S173948","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36504509","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":"1-, 3-, and 5-year survival among early-stage lung cancer patients treated with lobectomy vs SBRT.","authors":"Denise Albano,&nbsp;Thomas Bilfinger,&nbsp;Barbara Nemesure","doi":"10.2147/LCTT.S166320","DOIUrl":"https://doi.org/10.2147/LCTT.S166320","url":null,"abstract":"<p><strong>Background: </strong>Lobectomy has traditionally been recommended for fit patients diagnosed with early-stage non-small-cell lung cancer (NSCLC). Recently, however, stereotactic body radiotherapy (SBRT) has been introduced as an alternative treatment option. The purpose of this investigation is to compare survival outcomes for individuals with stage I/II NSCLC treated with lobectomy vs SBRT.</p><p><strong>Methods: </strong>This retrospective study included 191 patients (100 surgery, 91 SBRT) identified through the Lung Cancer Evaluation Center, Stony Brook, NY, between 2008 and 2012. Survival and recurrence rates were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models to adjust for possible confounders. A subset of cases was propensity-matched to address potential differences in health status between groups.</p><p><strong>Results: </strong>1-, 3-, and 5-year survival outcomes were significantly better among patients undergoing lobectomy vs SBRT. Survival rates at 3 years were 92.8% and 59.0% (<i>p</i><0.001) in the 2 groups, respectively. Propensity-matched analyses indicated similar findings. Recurrence rates were likewise lower among patients undergoing surgery (7.1% vs 21.0%, <i>p</i><0.01 at 3 years); however, statistical significance was not maintained in the propensity-matched analysis.</p><p><strong>Conclusion: </strong>These findings add to a growing evidence base supporting the use of lobectomy vs SBRT in the treatment of lung cancer among healthy, early-stage NSCLC patients.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"65-71"},"PeriodicalIF":3.6,"publicationDate":"2018-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S166320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36476587","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":"Prophylactic cranial irradiation in small-cell lung cancer: update on patient selection, efficacy and outcomes.","authors":"Farkhad Manapov,&nbsp;Lukas Käsmann,&nbsp;Olarn Roengvoraphoj,&nbsp;Maurice Dantes,&nbsp;Nina-Sophie Schmidt-Hegemann,&nbsp;Claus Belka,&nbsp;Chukwuka Eze","doi":"10.2147/LCTT.S137577","DOIUrl":"https://doi.org/10.2147/LCTT.S137577","url":null,"abstract":"<p><p>Over 10% of small-cell lung cancer (SCLC) patients have brain metastases (BM) at initial diagnosis; more than 50% will develop BM within 2 years. BM are detected in up to 80% of all patients at autopsy. After primary treatment, prophylactic cranial irradiation (PCI) has been established as standard of care in SCLC patients responding to initial therapy. Based on level I evidence, PCI significantly decreases the risk of intracranial relapse and shows a modest survival benefit after 3 years. However, the role of PCI in defined patient subgroups such as resected SCLC, elderly and extensive stage patients with access to magnetic resonance imaging surveillance and stereotactic radiotherapy is yet to be fully clarified. Furthermore, strategies to effective prevention of neurocognitive decline after PCI remain unclear. All these factors significantly impact treatment decision making and should be evaluated in prospective settings. New concepts such as hippocampal avoidance and drug neuroprotection prevent chronic neurocognitive effects reducing treatment-related side effects of PCI. The aim of this review is to present a summary and update of the latest evidence for patient selection, efficacy and outcome of PCI.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"49-55"},"PeriodicalIF":3.6,"publicationDate":"2018-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S137577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36631944","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":"Response to rapamycin analogs but not PD-1 inhibitors in PTEN-mutated metastatic non-small-cell lung cancer with high tumor mutational burden.","authors":"Ankur R Parikh,&nbsp;Siraj M Ali,&nbsp;Alexa B Schrock,&nbsp;Lee A Albacker,&nbsp;Vincent A Miller,&nbsp;Phil J Stephens,&nbsp;Pamela Crilley,&nbsp;Maurie Markman","doi":"10.2147/LCTT.S161738","DOIUrl":"https://doi.org/10.2147/LCTT.S161738","url":null,"abstract":"<p><p>In non-small-cell lung cancer (NSCLC) refractory to standard therapy and which lacks well-known oncogenic drivers, genomic profiling can still identify genomic alterations that may suggest potential sensitivity to targeted therapy. PTEN mutation in NSCLC may be sensitizing to analogs of rapamycin such as everolimus or temsirolimus, but more investigation is needed. We report the case of a patient with metastatic NSCLC harboring a PTEN mutation as well as high tumor mutational burden and PD-L1 positivity with a durable response to temsirolimus, but refractory to a checkpoint inhibitor. Even in the event of failure of treatment with checkpoint inhibitors in the background of a case with a higher tumor mutational burden and PD-L1 positivity, targeting specific genomic alterations may still result in patient benefit.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"45-47"},"PeriodicalIF":3.6,"publicationDate":"2018-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S161738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36174135","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}