Lung Cancer最新文献

{"title":"Entrectinib versus crizotinib in Asian patients with ROS1-positive non-small cell lung cancer: A matching-adjusted indirect comparison","authors":"Yongfeng Yu ,&nbsp;Yun Fan ,&nbsp;Xiaorong Dong ,&nbsp;Juan Li ,&nbsp;Yan Yu ,&nbsp;Jun Zhao ,&nbsp;Sha Tao ,&nbsp;Yujun Chen ,&nbsp;Mo Chen ,&nbsp;Yueming Liu ,&nbsp;Jiahui Xu ,&nbsp;Qiaonan Zhu ,&nbsp;Xichun Hu ,&nbsp;Shun Lu","doi":"10.1016/j.lungcan.2024.108018","DOIUrl":"10.1016/j.lungcan.2024.108018","url":null,"abstract":"<div><h3>Objectives</h3><div>Entrectinib and crizotinib are the only <em>ROS</em> proto-oncogene 1 receptor (ROS1) tyrosine kinase inhibitors available for most Asian patients. Their efficacy has neither been compared directly in clinical trials in patients with <em>ROS1</em>-positive non-small cell lung cancer (NSCLC), nor indirectly in Asian populations. Thus, we aimed to provide comparative evidence of the efficacy and safety of entrectinib and crizotinib for Asian patients with advanced or metastatic <em>ROS1</em>-positive NSCLC.</div></div><div><h3>Materials and Methods</h3><div>Efficacy, including overall survival (OS) and progression-free survival (PFS), and safety were evaluated using an unanchored matching-adjusted indirect comparison (MAIC). Individual patient data (IPD) from entrectinib trials (ALKA-372–001/EudraCT 2012–000148-88, STARTRK-1/NCT02097810, and STARTRK-2/NCT02568267; dosage, ≥600 mg once daily; enrollment cutoff, 02 July 2020; data cutoff, 02 August 2021) and aggregate data with simulated pseudo-IPD from a crizotinib trial (OxOnc/NCT01945021; dosage, 250 mg twice daily) were analyzed. Key eligibility criteria from the crizotinib trial were applied to IPD from the entrectinib trials. Baseline characteristics were match-adjusted between arms using propensity score weighting.</div></div><div><h3>Results</h3><div>Fifty-two and 127 patients from the entrectinib and crizotinib trials, respectively, were available for evaluation. Median OS was not reached (NR; weighted; 95 % confidence interval [CI] 28.3–NR) in the entrectinib arm and 44.2 months (95 % CI 32.0–NR) in the crizotinib arm (hazard ratio [HR], 0.662; 95 % CI 0.32–1.37). The respective median PFS was 39.4 months (weighted; 95 % CI 10.4–46.8) and 15.9 months (95 % CI 12.9–24.0) (HR, 0.688; 95 % CI 0.37–1.27). Most AEs were Grade 1–2; both drugs were generally well tolerated. Neutropenia was the most common Grade 3 or 4 treatment-related adverse event for both entrectinib and crizotinib.</div></div><div><h3>Conclusions</h3><div>The outcomes in this MAIC study including Asian patients with <em>ROS1</em>-positive NSCLC showed a trend for greater clinical benefit with entrectinib versus crizotinib. These findings may contribute to better-informed treatment decisions.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108018"},"PeriodicalIF":4.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter regarding “The significance of inflammatory markers in prognosticating the effectiveness and safety of immunotherapy in conjunction with chemotherapy during the primary intervention of advanced non-small cell lung carcinoma”","authors":"Nanami Kosaka,&nbsp;Yuki Kataoka","doi":"10.1016/j.lungcan.2024.108020","DOIUrl":"10.1016/j.lungcan.2024.108020","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108020"},"PeriodicalIF":4.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive serum biomarker analysis reveals IL-8 changes as the only predictor of the effectiveness of immune checkpoint inhibitors for patients with advanced non-small cell lung cancer","authors":"Hiroaki Akamatsu ,&nbsp;Yasuhiro Koh ,&nbsp;Makoto Nishio ,&nbsp;Yasushi Goto ,&nbsp;Hidetoshi Hayashi ,&nbsp;Satoru Miura ,&nbsp;Koji Tamada ,&nbsp;Hiroshi Kagamu ,&nbsp;Akihiko Gemma ,&nbsp;Ichiro Yoshino ,&nbsp;Toshihiro Misumi ,&nbsp;Atsuto Mouri ,&nbsp;Ryota Saito ,&nbsp;Naoto Takase ,&nbsp;Noriko Yanagitani ,&nbsp;Hiroshi Nokihara ,&nbsp;Masahiro Seike ,&nbsp;Kei Takamura ,&nbsp;Masahide Mori ,&nbsp;Shunichiro Iwasawa ,&nbsp;Tetsuya Mitsudomi","doi":"10.1016/j.lungcan.2024.108017","DOIUrl":"10.1016/j.lungcan.2024.108017","url":null,"abstract":"<div><h3>Objectives</h3><div>Programmed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting.</div></div><div><h3>Materials and Methods</h3><div>This was a sub-study of J-TAIL, a prospective observational study of atezolizumab monotherapy in pre-treated patients with advanced NSCLC. From April to October 2019, 262 patients were enrolled from 73 sites in Japan. Serum samples were collected at baseline and at the second dose of atezolizumab. Quantification of the 51 serum cytokines, chemokines, growth factors, and vascular endothelial growth factors was performed using the Luminex platform. Baseline values and fold changes of the time of the second dose to the baseline were examined in association with the effectiveness of atezolizumab.</div></div><div><h3>Results</h3><div>Among the 51 proteins assessed, a higher baseline interleukin (IL)-12 level, a higher soluble CD40 ligand fold change, a lower IL-8 fold change were associated with higher objective response rate (ORR). Of these, only the lower IL-8 fold change was associated with better progression-free survival (PFS) (adjusted hazard ratio, 1.98; 95 % confidence interval, 1.45–2.70; <em>P</em> &lt; 0.01). Multivariate analysis demonstrated that the lower IL-8 fold change was an independent factor for both the ORR and PFS. The IL-8 fold change was independent of the neutrophil/lymphocyte ratio, and durable PFS was observed in patients with both low.</div></div><div><h3>Conclusion</h3><div>Comprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108017"},"PeriodicalIF":4.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective treatment strategies and key factors influencing therapeutic efficacy in advanced SMARCA4-deficient non-small cell lung cancer","authors":"Hui Liu ,&nbsp;Qiyuan Hong ,&nbsp;Shuohan Zheng ,&nbsp;Meifang Zhang ,&nbsp;Ling Cai","doi":"10.1016/j.lungcan.2024.108022","DOIUrl":"10.1016/j.lungcan.2024.108022","url":null,"abstract":"<div><h3>Introduction</h3><div>SMARCA4/BRG1-deficient non-small cell lung cancer (SD-NSCLC) with high invasiveness and poor prognosis is associated with primary resistance to standard treatment, especially in late-stage patients. This study aimed to explore effective treatments and identify critical factors impacting therapeutic efficacy to enhance outcomes for SD-NSCLC patients.</div></div><div><h3>Methods</h3><div>103 SD-NSCLC patients in stage III/IV diagnosed by immunohistochemistry from May 2019 to March 2024 were included in this study. We assessed the patients’ clinical and genetic features, analyzed the clinical outcomes of local treatment and immunotherapy according to the TNM stage, and further evaluated the factors impacting therapeutic efficacy.</div></div><div><h3>Results</h3><div>In stage III patients, no significant differences in the median progression-free survival (mPFS) and median overall survival (mOS) were observed between patients receiving local treatment at the primary site and those who did not (p &gt; 0.05), while adding ICIs (immune checkpoint inhibitors) to local treatment significantly improved mPFS compared with non-ICIs (15.0 vs. 7.7 months, p = 0.033), though not mOS (p &gt; 0.05). For stage IV patients, ICIs significantly improved mPFS (8.9 vs. 4.2 months, p = 0.006) and mOS (19.7 vs. 13.1 months, p = 0.007) compared to non-ICIs treatments. However, among ICIs-treated patients, the addition of local treatment to the primary lesion did not significantly affect mPFS and mOS (p &gt; 0.05). Patients with <em>STK11/KEAP1</em> mutations had significantly shorter mPFS (3.6 vs. 16.2 months, p = 0.001) and mOS (17.7 vs. 31.3 months, p = 0.002), while no significant difference was observed in mPFS and mOS in patients with different tumor mutation burden (TMB) and PD-L1 expression levels.</div></div><div><h3>Conclusion</h3><div>The addition of ICIs to local treatment shows promising results for locally advanced patients with SD-NSCLC, and first-line ICIs are associated with improved survival in metastatic SD-NSCLC. <em>STK11</em>/<em>KEAP1</em> mutations may be linked to reduced efficacy of immunotherapy.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108022"},"PeriodicalIF":4.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuing immune checkpoint inhibitors after progression: Real-world patterns of care and outcomes in second-line treatment for extensive-stage small-cell lung cancer.","authors":"Baishen Zhang, Hejing Bao, Zhanquan Li, Jing Chen, Hui Yu, Meichen Li, Muyan Cai, Likun Chen","doi":"10.1016/j.lungcan.2024.108021","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108021","url":null,"abstract":"<p><strong>Introduction: </strong>Small cell lung cancer (SCLC) is a highly malignant tumor with an extremely poor prognosis. In the currentera of immunotherapy, the role of immune checkpoint inhibitors (ICIs) in the second-line treatment of patients with extensive-stage SCLC (ES-SCLC) who have progressed to initial chemoimmunotherapy remains unclear.</p><p><strong>Methods: </strong>A multicenter retrospective study were conducted, involving patients with ES-SCLC who received second-line (2L) therapy after progression to first-line chemoimmunotherapy. Patients were divided into 2L-ICIs group and 2L-non-ICIs group according to whether ICIs were added to the 2L treatment. The efficacy and adverse events of the two groups were analyzed and compared.</p><p><strong>Results: </strong>A total of 103 patients were included in this study, with 53 in the 2L-ICIs group and 50 in the 2L-non-ICIs group. The 2L-ICIs group demonstrated a longer median progression-free survival (PFS) compared to the 2L-non-ICIs group (4.4 months vs 3.9 months, HR = 0.45, p = 0.001). Similarly, median overall survival was also prolonged in the 2L-ICIs group (10.0 months vs 6.9 months, HR = 0.56, p = 0.015). Cox regression analysis revealed that the addition of ICIs to 2L treatment was an independent prognostic factor for both PFS and OS in ES-SCLC patients. Subgroup analysis indicated that patients with a first-line PFS of ≥6 months could potentially benefit more from 2L ICIs. Furthermore, the occurrence of adverse events in the two groups exhibited a similar pattern.</p><p><strong>Conclusion: </strong>For ES-SCLC patients who have progressed to first-line chemoimmunotherapy, adding ICIs to second-line treatment may be considered as an option with limited benefit but manageable adverse effects.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108021"},"PeriodicalIF":4.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOTCH and PTP4A3 alterations emerge as novel predictive biomarkers and potential therapeutic targets in pleural mesothelioma","authors":"Mariacarmela Santarpia ,&nbsp;Marta Aliprandi ,&nbsp;Calogera Claudia Spagnolo ,&nbsp;Amir Avan ,&nbsp;Rafael Rosell ,&nbsp;Paolo Andrea Zucali ,&nbsp;Elisa Giovannetti","doi":"10.1016/j.lungcan.2024.108024","DOIUrl":"10.1016/j.lungcan.2024.108024","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies showed opposite effects of NOTCH1 and NOTCH2 on mesothelioma cell survival under hypoxia. Mechanisms underlying these effects are not still clear and this pathway plays a key role in angiogenesis and cancer stem cells (CSCs) self-renewal processes.</div></div><div><h3>Purpose</h3><div>In this study we evaluated whether NOTCH1, NOTCH2 copy number alterations (CNAs) might predict prognosis of patients with pleural mesothelioma (PM) and if the modulation of this pathway might target CSCs, potentiating pemetrexed activity, also in hypoxic conditions.</div></div><div><h3>Methods</h3><div>Recurrent CNAs were determined by high-resolution whole-genome sequencing from paraffin-embedded samples of a “discovery cohort” (26 patients treated with pemetrexed-based chemotherapy). Prognostic CNAs were validated by PCR gene copy-number and expression analyses in the “discovery” and in two independent “validation” cohorts of pemetrexed-treated and untreated patients (N = 45 and N = 40). Functional analyses of emerging genes were performed through siRNA in different subpopulation of PM cells, growing under hypoxia.</div></div><div><h3>Results</h3><div>A copy number gain of NOTCH2 was observed in 50% of patients with progressive disease and its overexpression correlated with a worse prognosis in both pemetrexed-treated and untreated-patients’ cohorts. Conversely, losses of PTP4A3 correlated with clinical benefit, while patients with overexpression of both NOTCH2 and PTP4A3 had the worse prognosis. Moreover, NOTCH2 silencing through siRNA in vitro reduced migration, enhancing apoptosis of PM cells, while the PTP4A3 inhibitor BR-1 overcame pemetrexed resistance in PM cells characterized by high NOTCH2/PTP4A3 expression.</div></div><div><h3>Conclusions</h3><div>NOTCH2 and PTP4A3 alterations are associated with clinical outcomes in pemetrexed-treated PM patients. The inhibition of NOTCH pathway may be exploited to eradicate CSCs and improve patients’ survival.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108024"},"PeriodicalIF":4.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact of preoperative sarcopenia and immunonutritional impairment on postoperative outcomes in non-small cell lung cancer surgery","authors":"Atsuki Uchibori,&nbsp;Satoru Okada,&nbsp;Masanori Shimomura,&nbsp;Tatsuo Furuya,&nbsp;Chiaki Nakazono,&nbsp;Tomoki Nishimura,&nbsp;Masayoshi Inoue","doi":"10.1016/j.lungcan.2024.108004","DOIUrl":"10.1016/j.lungcan.2024.108004","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to clarify the relationship between preoperative sarcopenia and prognostic nutritional index (PNI) statuses and clinicopathological factors in patients with non-small cell lung cancer (NSCLC) who underwent surgical resection, and to evaluate short- and long-term outcomes by stratifying groups according to sarcopenia and PNI status as prognostic predictors.</div></div><div><h3>Materials and methods</h3><div>This study included 300 patients with p-Stage I-IIIA NSCLC who underwent complete resection with lobectomy. Sarcopenia was assessed using the skeletal muscle index (SMI) and the immunonutritional index was evaluated using the PNI. The first quartile was used as the cutoff for the sarcopenia/non-sarcopenia and low/high-PNI groups.</div></div><div><h3>Results</h3><div>The median patient age was 70 years, and 184 patients (61.3 %) were male individuals. The median PNI was 50.2, and the median SMI was 48.1 and 37.5 for male and female patients, respectively. The median follow-up period was 64 months (60 patients died). Survival analysis showed that overall survival was significantly worse in the sarcopenia and low-PNI groups than in the control group (<em>p</em> = 0.002 and <em>p</em> &lt; 0.001, respectively). When stratified by sarcopenia and PNI status, the sarcopenia with low-PNI group had a particularly poor prognosis (5-year survival rate, 52.8 % [<em>p</em> &lt; 0.001]). Multivariable Cox regression analysis revealed that sarcopenia with low PNI was an independent prognostic factor that indicated a poor outcome. The response to drug treatment for postoperative recurrence was significantly worse in the sarcopenia with low-PNI group than in<!--> <!-->the other group.</div></div><div><h3>Conclusion</h3><div>The combination of preoperative sarcopenia and immunonutritional impairment had a negative clinical impact independent of tumor factors, and patients with these two indications had a particularly poor prognosis. These factors may be associated with poor responses to drug treatment for postoperative recurrence. The evaluation of skeletal muscle mass using preoperative imaging and nutritional assessment using serum markers may be useful for perioperative management and prognosis prediction.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108004"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical benefit evaluation of drug treatment regimens for advanced lung cancer:based on ASCO-VF and ESMO-MCBS","authors":"Jingdan Pang ,&nbsp;Yiruo Zhang ,&nbsp;Xuan Wang ,&nbsp;Wentian Wu ,&nbsp;Chang Wan ,&nbsp;Ziming Li ,&nbsp;Yingying Du","doi":"10.1016/j.lungcan.2024.108001","DOIUrl":"10.1016/j.lungcan.2024.108001","url":null,"abstract":"<div><h3>Background</h3><div>With the increasing use of novel targeted drugs and immune checkpoint inhibitors (ICIs) for lung cancer (LC), the life expectancy of patients with LC has notably increased. In China, many drugs with the same mechanism of action have been approved by the National Medical Products Administration (NMPA) through phase III randomized controlled trials (RCTs). However, differences occur in these drugs’ efficacy and adverse effects, all of which have been compared with standard treatments, and data from head-to-head studies are lacking.</div></div><div><h3>Methods</h3><div>The key RCTs of EGFR tyrosine kinase inhibitors (EGFR-TKIs), ALK-TKIs, and ICIs approved by NMPA in advanced LC in China were searched and divided into five groups. The American Society of Clinical Oncology Value Framework (ASCO-VF v2) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS v1.1) were used to evaluate the net health benefits (NHB) of RCTs, including efficacy, adverse reactions, and patient-reported outcomes (PROs), etc. The consistency of the ASCO-VF and ESMO-MCBS was compared.</div></div><div><h3>Results</h3><div>As of September 2024, 37 RCTs have been included in the ASCO-VF and ESMO-MCBS. NHB scores ranged from 12.30 to 93.25. Nineteen trials met the ASCO-VF “substantial benefit”, and 28 trials achieved the ESMO-MCBS “substantial benefit”. Except for icotinib, dacomitinib, and befotertinib, all EGFR-TKIs and ALK-TKIs met the threshold of two frameworks. In the ICI regimens, eight regimens met the threshold of “ substantial benefit ” as defined by the two frameworks and nine studies showed conflicting results. The correlation coefficient of the 37 pairs of scores in the advanced LC study was estimated to be 0.473(Spearman), and the consistency analysis showed fair agreement.(κ = 0.265, p = 0.001).</div></div><div><h3>Conclusions</h3><div>ASCO-VF and ESMO-MCBS focus on clinical efficacy and consider the adverse effects of drugs and PROs. We look forward to head-to-head studies on the different treatment options and advocate refining the ESMO-MCBS.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 108001"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alectinib combined with cobimetinib in ALK-Rearranged lung Cancer: A phase IB study","authors":"Ibiayi Dagogo-Jack ,&nbsp;Alissa J. Cooper ,&nbsp;Bruce E. Johnson ,&nbsp;Justin F. Gainor ,&nbsp;Jessica J. Lin ,&nbsp;Lecia V. Sequist ,&nbsp;Zofia Piotrowska ,&nbsp;Subba R. Digumarthy ,&nbsp;Mari Mino-Kenudson ,&nbsp;Alona Muzikansky ,&nbsp;Alice T. Shaw","doi":"10.1016/j.lungcan.2024.108003","DOIUrl":"10.1016/j.lungcan.2024.108003","url":null,"abstract":"<div><h3>Introduction</h3><div>Anaplastic lymphoma kinase rearranged (ALK + ) lung cancers often develop ALK-independent resistance mechanisms that reactivate the mitogen-activated protein kinase pathway signaling pathway. We therefore evaluated alectinib combined with the MEK inhibitor cobimetinib in metastatic ALK + lung cancer.</div></div><div><h3>Materials and Methods</h3><div>This phase Ib study employed a 3 + 3 design. Cohort 1 enrolled patients irrespective of prior alectinib exposure. Cohort 2 only enrolled treatment-naive patients. Patients received alectinib 600 mg twice daily (BID) continuously and cobimetinib at either 20 or 40 mg daily on days 1–21 every 28 days. A 2-week alectinib lead-in was incorporated into cohort 2. The primary objective was to determine the maximum tolerated dose (MTD) for cohort 1.</div></div><div><h3>Results</h3><div>Sixteen patients were enrolled between 9/2017 and 8/2021, ten of whom were in cohort 1. No dose-limiting toxicities (DLTs) were observed with alectinib + cobimetinib 20 mg in cohort 1. On alectinib + cobimetinib 40 mg, DLTs of grade 3–4 creatine phosphokinase elevation and grade 3 rash were observed in 2 of 6 patients, both of whom were alectinib-naïve and required dose reduction. The MTD for cohort 1 was declared as 600 mg alectinib BID + cobimetinib 40 mg. Six alectinib-naïve patients were treated with alectinib + cobimetinib 20 mg in cohort 2. With the lead-in, no patients experienced DLTs. One patient in cohort 2 discontinued cobimetinib for grade 2 pneumonitis. Median progression-free survival was 2.2 months and 49.2 months for alectinib-resistant and alectinib-naïve patients, respectively.</div></div><div><h3>Discussion</h3><div>Alectinib combined with cobimetinib demonstrated limited activity in alectinib-resistant tumors. Despite dose-limiting dermatologic and muscle enzyme toxicities, durable responses were observed in alectinib-naïve patients.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108003"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Real-world treatment sequencing and effectiveness of second- and third-generation ALK tyrosine kinase inhibitors for ALK -positive advanced non-small cell lung cancer” [Lung Cancer 195 (2024) 107919]","authors":"Jessica R. Bauman ,&nbsp;Geoffrey Liu ,&nbsp;Isabel Preeshagul ,&nbsp;Stephen V. Liu ,&nbsp;Barbara Melosky ,&nbsp;Devin Abrahami ,&nbsp;Benjamin Li ,&nbsp;Despina Thomaidou ,&nbsp;Kirsten Duncan ,&nbsp;Stan Krulewicz ,&nbsp;Martin Rupp ,&nbsp;Jessica J. Lin","doi":"10.1016/j.lungcan.2024.108000","DOIUrl":"10.1016/j.lungcan.2024.108000","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 108000"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}