Lung Cancer: Targets and Therapy最新文献

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Co-Occurring EGFR S645C and EGFR L858R in a Patient with Lung Adenocarcinoma Induced Primary Resistance to Osimertinib. 在肺腺癌患者中同时发生EGFR S645C和EGFR L858R诱导对奥西美替尼的原发性耐药性。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-10-09 eCollection Date: 2023-01-01 DOI: 10.2147/LCTT.S431252
Li Wang, Fei Quan, Zhen Guo, Zhongyu Lu, Duoxia Yang, Meiqi Shi
{"title":"Co-Occurring EGFR S645C and EGFR L858R in a Patient with Lung Adenocarcinoma Induced Primary Resistance to Osimertinib.","authors":"Li Wang,&nbsp;Fei Quan,&nbsp;Zhen Guo,&nbsp;Zhongyu Lu,&nbsp;Duoxia Yang,&nbsp;Meiqi Shi","doi":"10.2147/LCTT.S431252","DOIUrl":"10.2147/LCTT.S431252","url":null,"abstract":"<p><p>Approximately 10-20% of patients demonstrate primary resistance to EGFR-TKIs, and different EGFR mutations vary in sensitivity to EGFR-TKIs. We report a case of a 78-year-old male with lung adenocarcinoma that EGFR L858R (AF = 1.32%) coexisting with EGFR S645C (AF = 7.13%) in his diagnosed tissues analyzed by NGS. The patient was primarily resistant to first-line osimertinib and rapidly progressed after pembrolizumab in combination with pemetrexed and bevacizumab, as demonstrated by persistently elevated CEA levels during treatment. ctDNA-based NGS analysis revealed loss of EGFR L858R while persistence of highly abundant EGFR S645C in the pleural fluid and plasma after treatment, suggesting that EGFR L858R may be a subclone. We provide the first clinical evidence of the primary resistance of EGFR S645C to osimertinib and emphasize the importance of identifying clones and subclones. Our patient did not respond to immunotherapy either, and preclinical studies have shown that EGFR S645C activates the MEK signaling pathway, the combination of EGFR-TKIs and MEK inhibitors may be effective.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/ba/lctt-14-79.PMC10576154.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236581","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}
引用次数: 0
The Additional Exclusions of ROS1 Fusions (In Addition to EGFR Mutation and ALK Fusions) in the Cemiplimab NSCLC FDA Indication (EMPOWER-Lung 1 and -Lung 3). Catching Up with Current Scientific View of Immunotherapy in Never-Smoker Predominant Actionable Driver Mutation Positive NSCLC? 在 Cemiplimab NSCLC FDA 适应症(EMPOWER-肺 1 和-肺 3)中额外排除 ROS1 融合(除 EGFR 突变和 ALK 融合外)。了解免疫疗法在以不吸烟者为主的可作用驱动基因突变阳性 NSCLC 中的当前科学前景?
IF 5.1
Lung Cancer: Targets and Therapy Pub Date : 2023-06-23 eCollection Date: 2023-01-01 DOI: 10.2147/LCTT.S413611
Danielle Brazel, Saihong Ignatius Ou
{"title":"The Additional Exclusions of <i>ROS1</i> Fusions (In Addition to <i>EGFR</i> Mutation and <i>ALK</i> Fusions) in the Cemiplimab NSCLC FDA Indication (EMPOWER-Lung 1 and -Lung 3). Catching Up with Current Scientific View of Immunotherapy in Never-Smoker Predominant Actionable Driver Mutation Positive NSCLC?","authors":"Danielle Brazel, Saihong Ignatius Ou","doi":"10.2147/LCTT.S413611","DOIUrl":"10.2147/LCTT.S413611","url":null,"abstract":"<p><p>Cemiplimab is one of seven immune checkpoint inhibitors (ICIs) approved for the first-line (1L) treatment of advanced NSCLC in the US based on EMPOWER-Lung 1 and -Lung 3 trials. In addition to exclusion of NSCLC patients harboring <i>EGFR</i> mutations and <i>ALK</i> fusion from 1L treatment with ICIs, exclusion of <i>ROS1</i> fusion is an additional unique exclusion the use of criterion for cemiplimab in the US FDA indication based on the design of the EMPOWER lung trials. We review the effectiveness of ICIs in never-smoker predominant NSCLC with driver mutations (<i>EGFR, ALK, ROS1, RET, HER2</i>) and question whether exclusion of <i>ROS1</i> fusion would put cemiplimab at a competitive disadvantage given the requirement for insurance to prove <i>ROS1</i> fusion negativity. We further discuss whether the US FDA as a regulatory authority has the right and responsibility to harmonize the use of ICIs in these actionable driver mutations to standardize community practice for the benefit of patients and to advance the development of next-generation treatment for these driver mutations.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/bc/lctt-14-63.PMC10296535.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9734409","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}
引用次数: 0
CodeBreak 200: Sotorasib Has Not Broken the KRASG12C Enigma Code. 密码破解200:Sotorasib没有破解KRASG12C谜码。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/LCTT.S403461
Shannon S Zhang, Alexandria Lee, Misako Nagasaka
{"title":"CodeBreak 200: Sotorasib Has Not Broken the KRAS<sup>G12C</sup> Enigma Code.","authors":"Shannon S Zhang,&nbsp;Alexandria Lee,&nbsp;Misako Nagasaka","doi":"10.2147/LCTT.S403461","DOIUrl":"https://doi.org/10.2147/LCTT.S403461","url":null,"abstract":"<p><p>Thirteen percent of non-small cell lung cancer (NSCLC) patients are estimated to have the KRAS G12C mutation. Sotorasib is a novel KRAS G12C inhibitor that has shown promising results in preclinical and clinical studies, granting its conditional approval by the FDA in May 2021. The phase I clinical trial resulted in a confirmed response of 32% and progression free survival (PFS) of 6.3 months while the phase II trial resulted in a confirmed response of 37.1% and a PFS of 6.8 months. It was also shown to be tolerable with most subjects experiencing grade one or two adverse events, most commonly diarrhea and nausea. The CodeBreaK 200 phase III trial data have recently resulted and showed an improved PFS with the use of sotorasib at 5.6 months compared to that of standard docetaxel of 4.5 months in locally advanced or unresectable metastatic KRAS G12C NSCLC previously treated with at least one platinum-based chemotherapy and checkpoint inhibitor. The lower than expected PFS of sotorasib from the phase III trial opens up opportunities for other G12C inhibitors to join the field. Indeed, adagrasib, another G12C inhibitor just recently gained FDA accelerated approval in NSCLC patients based on the KRYSTAL-1 study where the response rate was 43% with a median duration of response of 8.5 months. With novel agents and combinations, the field of KRAS G12C is quickly evolving. While sotorasib was an exciting start, there is more to do to break the KRAS G12C Enigma code.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/77/lctt-14-27.PMC10123019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9356679","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}
引用次数: 0
Tiragolumab (Anti-TIGIT) in SCLC: Skyscraper-02, a Towering Inferno. Tiragolumab (Anti-TIGIT)用于SCLC: Skyscraper-02,一个高耸的地狱。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/LCTT.S379389
Danielle Brazel, Sai-Hong Ignatius Ou, Misako Nagasaka
{"title":"Tiragolumab (Anti-TIGIT) in SCLC: Skyscraper-02, a Towering Inferno.","authors":"Danielle Brazel,&nbsp;Sai-Hong Ignatius Ou,&nbsp;Misako Nagasaka","doi":"10.2147/LCTT.S379389","DOIUrl":"https://doi.org/10.2147/LCTT.S379389","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is characterized by rapid progression and poor prognosis. Although the phase II CITYSCAPE-02 trial found objective response rate (ORR) and progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients improved when tiragolumab was added to atezolizumab and chemotherapy, the phase III SKYSCRAPER-02 failed to find PFS or OS benefit in patients with SCLC. Atezolizumab was the first immunotherapy to show survival benefit in extensive SCLC based on the phase III IMpower133 study. Given that immunotherapy has become the standard of care for SCLC patients, further research is needed into ways to augment the immune system to better treat these patients.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/bc/lctt-14-1.PMC9831070.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10527555","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}
引用次数: 7
Effect of Lymphopenia on Tumor Response and Clinical Outcomes Following Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer. 淋巴细胞减少对III期非小细胞肺癌放化疗后肿瘤反应和临床结果的影响。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/LCTT.S386344
Jared Deck, Marissa Hartley, Mohammad Akhter, Dongliang Wang, Jeffrey A Bogart, Michael D Mix
{"title":"Effect of Lymphopenia on Tumor Response and Clinical Outcomes Following Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer.","authors":"Jared Deck,&nbsp;Marissa Hartley,&nbsp;Mohammad Akhter,&nbsp;Dongliang Wang,&nbsp;Jeffrey A Bogart,&nbsp;Michael D Mix","doi":"10.2147/LCTT.S386344","DOIUrl":"https://doi.org/10.2147/LCTT.S386344","url":null,"abstract":"<p><strong>Background: </strong>Prior studies suggest lymphopenia, systemic immune-inflammatory index, and tumor response all impact clinical outcomes in Stage III NSCLC. We hypothesized that tumor response after CRT would be associated with hematologic metrics and might predict clinical outcomes.</p><p><strong>Materials and methods: </strong>Patients with stage III NSCLC treated at a single institution between 2011 and 2018 were retrospectively reviewed. Pre-treatment gross tumor volume (GTV) was recorded then reassessed at 1-4 months post-CRT. Complete blood counts before, during and after treatment were recorded. Systemic immune-inflammation index (SII) was defined as neutrophil × platelet/lymphocyte. Overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier estimates, and compared with Wilcoxon tests. A multivariate analysis of hematologic factors impacting restricted mean survival was then performed using pseudovalue regression, accounting for other baseline factors.</p><p><strong>Results: </strong>106 patients were included. After median follow-up of 24 months, median PFS and OS were 16 and 40 months, respectively. Within the multivariate model, baseline SII was associated with OS (p = 0.046) but not PFS (p = 0.09), and baseline ALC correlated with both PFS and OS (p = 0.03 and p = 0.02, respectively). Nadir ALC, nadir SII, and recovery SII were not associated with PFS or OS.</p><p><strong>Conclusion: </strong>In this cohort of patients with stage III NSCLC, baseline hematologic factors were associated with clinical outcomes including baseline ALC, baseline SII and recovery ALC. Disease response was not well correlated with hematologic factors or clinical outcomes.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0b/79/lctt-14-47.PMC10204762.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9526461","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}
引用次数: 0
Clinical Utility and Application of Liquid Biopsy Genotyping in Lung Cancer: A Comprehensive Review. 肺癌液体活检基因分型的临床应用综述
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/LCTT.S388047
Maria Concetta Nigro, Paola Valeria Marchese, Chiara Deiana, Chiara Casadio, Linda Galvani, Alessandro Di Federico, Andrea De Giglio
{"title":"Clinical Utility and Application of Liquid Biopsy Genotyping in Lung Cancer: A Comprehensive Review.","authors":"Maria Concetta Nigro,&nbsp;Paola Valeria Marchese,&nbsp;Chiara Deiana,&nbsp;Chiara Casadio,&nbsp;Linda Galvani,&nbsp;Alessandro Di Federico,&nbsp;Andrea De Giglio","doi":"10.2147/LCTT.S388047","DOIUrl":"https://doi.org/10.2147/LCTT.S388047","url":null,"abstract":"<p><p>Precision medicine has revolutionized the therapeutic management of cancer patients with a major impact on non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma, where advances have been remarkable. Tissue biopsy, required for tumor molecular testing, has significant limitations due to the difficulty of the biopsy site or the inadequacy of the histological specimen. In this context, liquid biopsy, consisting of the analysis of tumor-released materials circulating in body fluids, such as blood, is increasingly emerging as a valuable and non-invasive biomarker for detecting circulating tumor DNA (ctDNA) carrying molecular tumor signatures. In advanced/metastatic NSCLC, liquid biopsy drives target therapy by monitoring response to treatment and identifying eventual genomic mechanisms of resistance. In addition, recent data have shown a significant ability to detect minimal residual disease in early-stage lung cancer, underlying the potential application of liquid biopsy in the adjuvant setting, in early detection of recurrence, and also in the screening field. In this article, we present a review of the currently available data about the utility and application of liquid biopsy in lung cancer, with a particular focus on the approach to different techniques of analysis for liquid biopsy and a comparison with tissue samples as well as the potential practical uses in early and advanced/metastatic NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/8b/lctt-14-11.PMC9904307.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242032","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}
引用次数: 2
From ASCEND-5 to ALUR to ALTA-3, an Anti-Climactic End to the Era of Randomized Phase 3 Trials of Next-Generation ALK TKIs in the Crizotinib-Refractory Setting. 从ASCEND-5到ALUR再到ALTA-3,新一代ALK TKIs在克唑替尼难治性环境中随机iii期试验时代的反高潮结束
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/LCTT.S413091
Alexandria T M Lee, Saihong Ignatius Ou
{"title":"From ASCEND-5 to ALUR to ALTA-3, an Anti-Climactic End to the Era of Randomized Phase 3 Trials of Next-Generation ALK TKIs in the Crizotinib-Refractory Setting.","authors":"Alexandria T M Lee,&nbsp;Saihong Ignatius Ou","doi":"10.2147/LCTT.S413091","DOIUrl":"https://doi.org/10.2147/LCTT.S413091","url":null,"abstract":"<p><p>The competing roles of various next-generation ALK TKIs in the first and second line treatment setting of advanced <i>ALK+</i> NSCLC were based on many phase 3 clinical trials in both the first-line and crizotinib-refractory settings. The approval of all next-generation ALK TKIs was first in the crizotinib-refractory setting, based on a large-scale Phase 2 trial, and was then followed by at least one global randomized phase 3 trial comparing to platinum-based chemotherapy (ASCEND-4) or to crizotinib (ALEX, ALTA-1L, eXalt3, CROWN). In addition, three randomized phase 3 trials in the crizotinib-refractory setting were also conducted by next-generation ALK TKIs that were developed earlier before the superiority of next-generation ALK TKIs was demonstrated in order to secure the approval of these ALK TKIs in the crizotinib-refractory setting. These three crizotinib-refractory randomized trials were: ASCEND-5 (ceritinib), ALUR (alectinib), and ALTA-3 (brigatinib). The outcome of the ATLA-3 trial was recently presented closing out the chapter where next-generation ALK TKIs were investigated in the crizotinib-refractory setting as they have replaced crizotinib as the standard of care first-line treatment of advanced <i>ALK+</i> NSCLC. This editorial summarizes the results of next-generation ALK TKIs in randomized crizotinib-refractory trials and provides a perspective on how natural history of <i>ALK+</i> NSCLC may potentially be altered with sequential treatment. ALTA-3 compared brigatinib to alectinib, showing that both achieved near identical blinded independent review committee (BIRC)-assessed progression-free survival (PFS) (19.2-19.3 months). Importantly, 4.8% of brigatinib-treated patients developed interstitial lung disease (ILD) while no alectinib-treated patients developed ILD. Dose reduction and discontinuation due to treatment-related adverse events were 21% and 5%, respectively, for brigatinib-treated patients compared to 11% and 2%, respectively, for alectinib-treated patients. Upon analysis of these findings, we speculate that brigatinib may have a diminishing role in the treatment of advanced <i>ALK+</i> NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/e1/lctt-14-57.PMC10292622.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9727116","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}
引用次数: 0
CodeBreaK 200: Sotorasib (AMG510) Has Broken the KRAS G12C+ NSCLC Enigma Code. CodeBreaK 200: Sotorasib (AMG510)破解了KRAS G12C+ NSCLC谜码。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/LCTT.S403614
Danielle Brazel, Jennifer Kim, Sai-Hong Ignatius Ou
{"title":"CodeBreaK 200: Sotorasib (AMG510) Has Broken the <i>KRAS G12C</i>+ NSCLC Enigma Code.","authors":"Danielle Brazel,&nbsp;Jennifer Kim,&nbsp;Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S403614","DOIUrl":"https://doi.org/10.2147/LCTT.S403614","url":null,"abstract":"<p><p>Per the US FDA sotorasib approval summary, <i>KRAS G12C</i> mutation is found in approximately 14% of adenocarcinoma of the lung, primarily in patients with a history of smoking. Until recently, targeted therapies against <i>KRAS G12C</i> have been largely unsuccessful due to the small protein size of <i>KRAS</i> and thus lack of binding pockets in <i>KRAS</i> and rapid hydrolysis of GTP to GDP by <i>KRAS</i> enzymes from abundance of GTP in the cytoplasm. Sotorasib, a first-in-class covalent <i>KRAS G12C</i> inhibitor that binds to the switch pocket II in the <i>KRAS G12C</i>-GDP \"off\" state, received US FDA accelerated approval on May 21, 2021 in the US, based on a Phase II dose expansion cohort of CodeBreaK 100 trial. Sotorasib at 960 mg once daily achieved an ORR of 36% (95% CI: 28%, 45%), with a median response duration of 10 months (range 1.3+, 11.1) in 124 <i>KRAS G12C</i>+ NSCLC. At the European Society of Medical Oncology (ESMO) 2022 annual meeting, sotorasib achieved a statistically significant improved PFS over docetaxel (HR = 0.66; 95% CI: 0. 51-0.86; P = 0.002). The modest magnitude of PFS improvement of 1.1 months (from 4.5 months to 5.6 months) and the ORR of 28% led to a vigorous debate on whether sotorasib was indeed a true breakthrough. In this pros and cons debate, we argue thatsotorasib has achieved a true breakthrough.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/26/lctt-14-31.PMC10124743.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9356681","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}
引用次数: 1
ALESIA 5-Year Update: Alectinib at 600 mg Twice Daily Gives Lorlatinib a Run for Its Money in Asia. ALESIA 5年更新:Alectinib 600毫克,每日两次,在亚洲与Lorlatinib竞争。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/LCTT.S419395
Alexandria T M Lee, Saihong Ignatius Ou
{"title":"ALESIA 5-Year Update: Alectinib at 600 mg Twice Daily Gives Lorlatinib a Run for Its Money in Asia.","authors":"Alexandria T M Lee,&nbsp;Saihong Ignatius Ou","doi":"10.2147/LCTT.S419395","DOIUrl":"https://doi.org/10.2147/LCTT.S419395","url":null,"abstract":"<p><p>Alectinib, a next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), has demonstrated superior progression-free survival over crizotinib with both 300 mg twice daily (J-ALEX) or 600 mg twice daily (ALEX, ALESIA) dosing in three pivotal clinical trials. Given the similar median PFS achieved in the J-ALEX trial and the Asian subgroup of the ALEX trial, there remains debate about the optimal alectinib dose for Asians. The third pivotal alectinib trial, ALESIA, which was conducted exclusively in Asia to support the registration of alectinib in China, utilized 600 mg alectinib twice daily. The mature PFS was not reached at the initial publication of ALESIA. At ESMO Asia 2022, the 5-year update of ALESIA was presented with an impressive mature investigator-assessed PFS of 41.6 months (95% CI 33.1-58.9), which is numerically longer than the mature PFS of 34.1 months achieved by alectinib at 300 mg twice daily in the J-ALEX trial. Based on these results, as well as retrospective pharmacokinetic and responses and PFS data, Alectinib at 600 mg twice daily is the optimal dose for Asians. This has been based on the ALESIA trial and on the retrospective pharmacokinetic and responses and PFS data and has set the benchmark for ALK TKI as the first-line treatment for advanced <i>ALK+</i> NSCLC in Asia. Importantly, lorlatinib, another next generation ALK TKI, also achieved an impressive hazard ratio with a still immature PFS in all patients, including Asian patients, in a recent subgroup analysis after a median follow-up time of 36.7 months. We await the final mature PFS of lorlatinib overall and for Asian patients in the CROWN trial to see if lorlatinib will set a new standard.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/56/lctt-14-71.PMC10335304.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10174331","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}
引用次数: 0
CheckMate-722: The Rise and Fall of Nivolumab with Chemotherapy in TKI-Refractory EGFR-Mutant NSCLC. checkate -722:纳武单抗联合化疗治疗tki难治性egfr突变NSCLC的兴衰
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2023-01-01 DOI: 10.2147/LCTT.S408886
Alexandria T M Lee, Misako Nagasaka
{"title":"CheckMate-722: The Rise and Fall of Nivolumab with Chemotherapy in TKI-Refractory EGFR-Mutant NSCLC.","authors":"Alexandria T M Lee,&nbsp;Misako Nagasaka","doi":"10.2147/LCTT.S408886","DOIUrl":"https://doi.org/10.2147/LCTT.S408886","url":null,"abstract":"<p><p>The treatment of non-small cell lung cancer (NSCLC) has increasingly been driven by the presence of targetable driver mutations, including epidermal growth factor receptor (EGFR) mutations. Tyrosine receptor inhibitors (TKIs) have subsequently emerged as the standard-of-care treatment for EGFR-mutant NSCLC. However, there are currently limited treatment options for TKI-refractory EGFR-mutant NSCLC. It is in this context that immunotherapy has arisen as a particularly promising player, especially in the context of favorable results from the ORIENT-31 and IMpower150 trials. Thus, the results of the CheckMate-722 trial were highly anticipated, as it was the first global trial to evaluate the efficacy of immunotherapy in addition to standard platinum-based chemotherapy, specifically in the treatment of EGFR-mutant NSCLC post-progression on TKIs.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/99/lctt-14-41.PMC10150033.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9762995","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}
引用次数: 0
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