Lung Cancer: Targets and Therapy最新文献

{"title":"MARIPOSA: Can Amivantamab and Lazertinib Replace Osimertinib in the Front-Line Setting?","authors":"D. Brazel, M. Nagasaka","doi":"10.2147/LCTT.S453974","DOIUrl":"https://doi.org/10.2147/LCTT.S453974","url":null,"abstract":"Abstract Osimertinib is the current first-line treatment for EGFR-mutated NSCLC, however, patients frequently relapse due to acquired resistance mutations. Amivantamab is a bispecific antibody against EGFR and MET alterations. Lazertinib is a tyrosine kinase inhibitor active against EGFR mutations including common resistance mutations. The MARIPOSA trial was designed to study if the combination of amivantamab plus lazertinib in untreated epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients would provide improved progression-free survival. Here, we discuss the rationale for the study and the early results of MARIPOSA.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760651","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":"Effectiveness and Safety of Anlotinib Combined with PD-1 Blockades in Patients with Previously Immunotherapy Treated Advanced Non-Small Cell Lung Cancer: A Retrospective Exploratory Study.","authors":"Xue-Jun Dou, Run-Yang Ma, De-Wang Ren, Qiang Liu, Peng Yan","doi":"10.2147/LCTT.S444884","DOIUrl":"10.2147/LCTT.S444884","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored.</p><p><strong>Results: </strong>The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3-35.9%) and a disease control rate of 85.1% (95% CI: 74.3-92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37-9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73-22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, <i>P</i>=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity.</p><p><strong>Conclusion: </strong>Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10979677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336193","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":"Overcoming Central β-Sheet #6 (Cβ6) <i>ALK</i> Mutation (L1256F), <i>TP53</i> Mutations and Short Forms of <i>EML4-ALK v3/b</i> and <i>v5a/b</i> Splice Variants are the Unmet Need That a Re-Imagined 5th-Generation (5G) ALK TKI Must Deliver.","authors":"Alexandria T M Lee, Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S446878","DOIUrl":"10.2147/LCTT.S446878","url":null,"abstract":"<p><p>Despite the development and approval of seven anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) spanning over three \"generations\" since the discovery of <i>ALK</i> fusion positive (<i>ALK+</i>) non-small cell lung cancer (NSCLC), there remains intrinsic and acquired resistances to these approved TKIs. Currently, a fourth-generation (4G) ALK TKI, NVL-655, is being developed to attack some of the unmet needs such as compound resistance mutations <i>in cis</i>. However, <i>EML4-ALK variant 3</i> and <i>TP53</i> mutations are intrinsic genomic alterations that negatively modulate efficacy of ALK TKIs. Potentially, in the shifting landscape where lorlatinib should be the first-line ALK TKI of choice based on the CROWN trial, the central β-sheet #6 (Cβ6) mutation <i>ALK L1256F</i> will be the potential acquired resistance mutation to lorlatinib which may be resistant to current ALK TKIs. Here we opine on what additional capacities a putative fifth-generation (5G) ALK TKI will need to possess if it can be achieved in one single molecule. We propose randomized trial schemas targeting some of the intrinsic resistance mechanisms that will lead to approval of a prototypic fifth-generation (5G) ALK TKI and actually be beneficial to <i>ALK+</i> NSCLC patients rather than just design a positive pivotal superiority trial for the sole purpose of drug approval.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10908247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022184","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":"Innovative Techniques in Video-Assisted Thoracoscopic Surgery: Lu's Approach.","authors":"Baofeng Wang, Jiang Wang, Tongyu Sun, Yilin Ding, Shasha Li, Hengxiao Lu","doi":"10.2147/LCTT.S446418","DOIUrl":"10.2147/LCTT.S446418","url":null,"abstract":"<p><strong>Purpose: </strong>Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from Uniportal Video-Assisted Thoracoscopic Surgery(UVATS), is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach.</p><p><strong>Patients and methods: </strong>The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected and analyzed. Patients were divided into the LVATS group and the UVATS group. Propensity score matching (PSM) was used to reduce selection bias and create two comparable groups. Perioperative variables were compared, and a p-value < 0.05 was deemed statistically significant.</p><p><strong>Results: </strong>A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144) min, P <0.001), less intraoperative blood loss (20 (20, 30) VS 25 (20, 50) mL, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50) cm, P <0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600) mL, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected (5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4) days, P =0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6) days, P = 0.608), VAS on the POD1 (4 (4, 4) VS 4 (4, 4), P=0.058) and POD3 (3 (3, 4) VS 4 (3, 4), P=0.219), and incidence of postoperative complications (P=0.521) between the two groups.</p><p><strong>Conclusion: </strong>Lu's approach for video-assisted thoracoscopic lobectomy is safe and feasible, potentially reducing surgery time, incision length, and intraoperative blood loss.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702880","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 Nail in the Coffin?: Examining the KEYNOTE-789 Clinical Trial’s Impact","authors":"Z. Arter, M. Nagasaka","doi":"10.2147/lctt.s443099","DOIUrl":"https://doi.org/10.2147/lctt.s443099","url":null,"abstract":"","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139633400","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":"Stage as the Sole \"Biomarker\" for Adjuvant Pembrolizumab in Resected Stage IB to IIIA NSCLC without Considerations for PD-L1 Expression Level, ALK/EGFR Mutational Status, and Prior Adjuvant Chemotherapy per FDA Approval Indications of PEARLS/Keynote-091?","authors":"Misako Nagasaka, Saihong Ignatius Ou","doi":"10.2147/LCTT.S433195","DOIUrl":"https://doi.org/10.2147/LCTT.S433195","url":null,"abstract":"<p><p>One of the most recent advancements in NSCLC was the approval of immunotherapy in the adjuvant setting. Both atezolizumab and pembrolizumab have been approved for the use in early stage NSCLC patients post resection. As it broadens the options for our patients, multiple approvals in the same setting are generally welcomed. However, there were important differences in the two studies that led to the approvals and the data could be confusing. Here we review IMpower010, the study that led to the first approval of atezolizumab in the adjuvant setting with comparison to the Keynote-091 study evaluating pembrolizumab in the adjuvant setting, gaining the most recent FDA approval for adjuvant use in early stage NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138796896","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":"Single-Cell Profiling of Tumor-Associated Neutrophils in Advanced Non-Small Cell Lung Cancer.","authors":"Jinpeng Shi, Jiayu Li, Haowei Wang, Xuefei Li, Qi Wang, Chao Zhao, Lei Cheng, Ruoshuang Han, Peixin Chen, Haoyue Guo, Zhuoran Tang, Caicun Zhou, Zhemin Zhang, Fengying Wu","doi":"10.2147/LCTT.S430967","DOIUrl":"https://doi.org/10.2147/LCTT.S430967","url":null,"abstract":"<p><strong>Purpose: </strong>Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.</p><p><strong>Materials and methods: </strong>We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.</p><p><strong>Results: </strong>Seven distinct TAN subtypes were defined, of which, the N₃ cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N₃ might be a pro-tumorigenic TAN subtype. N₁ and N₅ clusters were considered to be well differentiated and mature neutrophils based on <i>CXCR2</i> expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.</p><p><strong>Conclusion: </strong>Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460706","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":"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}

{"title":"CodeBreak 200: Sotorasib Has Not Broken the KRAS^G12C 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}

{"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,&nbsp;Saihong Ignatius Ou","doi":"10.2147/LCTT.S413611","DOIUrl":"https://doi.org/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":3.6,"publicationDate":"2023-01-01","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}