Lung Cancer: Targets and Therapy最新文献

{"title":"Evaluation of the Effectiveness and Safety Profile of First-Line Immune Checkpoint Inhibitors Combined with Chemotherapy in Pulmonary Sarcomatoid Carcinoma.","authors":"He Du, Xinyu Song, Fengying Wu","doi":"10.2147/LCTT.S494990","DOIUrl":"10.2147/LCTT.S494990","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary sarcomatoid carcinoma (PSC) represents a rare subtype of non-small cell lung cancer (NSCLC), and it has poor pathologic differentiation, aggressive progression, and early metastasis. Conventional antitumor therapies demonstrate limited efficacy against PSC, which is frequently associated with unfavorable clinical outcomes.</p><p><strong>Methods: </strong>We conducted an open-label, single-arm Phase II trial. This study has been registered with Clinical Trials (ChiCTR2000031478). Patients received immune checkpoint inhibitor (ICI) combination with chemotherapy, the treatment continued until disease progression, unacceptable toxicity, patient withdrawal, or death. The primary endpoint was objective response rate (ORR), with secondary endpoints comprising progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and treatment-emergent adverse events.</p><p><strong>Results: </strong>From March 2021 through August 2023, a total of 38 patients were enrolled. The study comprised predominantly male participants (91%, n=34) with a median age of 65.4 years. Notably, 86.8% (n=33) had smoking histories. The ORR and DCR were 73.7% and 94.7%, respectively. The median PFS was 13.3 months (95% CI, 10.2-15.7) and median OS was not reached. The most common immune-related adverse events were pneumonitis, the incidence of which was 13.2%. The majority of observed AEs were grades 1 or 2 and all AEs were manageable. Only two patients discontinued treatment due to grade 3 immune-related pneumonitis during the study.</p><p><strong>Conclusion: </strong>In our trial, we found that ICI combination with chemotherapy showed robust efficacy alongside acceptable toxicity in advanced-stage PSC. Taken together, ICI combination with chemotherapy could be a better option for PSC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"73-83"},"PeriodicalIF":5.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302431","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":"Elucidating the Role of FASN in Lung Cancer Stem Cells in Sensitive and Resistant EGFR-Mutated Non-Small Cell Lung Cancer Cells.","authors":"Emma Polonio-Alcalá, Sira Ausellé-Bosch, Gerard Riesco-Llach, Pablo Novales, Lidia Feliu, Marta Planas, Joaquim Ciurana, Teresa Puig","doi":"10.2147/LCTT.S512936","DOIUrl":"10.2147/LCTT.S512936","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer stem cells (CSCs) drive tumor initiation, relapse, and metastasis. Our research team developed polycaprolactone electrospun (PCL-ES) scaffolds for enriching lung CSCs (LCSCs) since monolayer culture do not allow the study of this malignant population. The upregulation of fatty acid synthase (FASN) correlates with resistance to tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR), and its inhibition induces cytotoxicity in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) cells. Therefore, this study aims to elucidate the role of FASN and related signaling pathways in LCSCs cultured in PCL-ES scaffolds and to evaluate the effectiveness of FASN inhibitor G28, a synthetic derivative of (-)-epigallocatechin-3-gallate (EGCG), against this population.</p><p><strong>Methods: </strong>EGFR-TKI-sensitive and -resistant cell modes were used. FASN expression and function were studied by RT-qPCR, Western blotting, and free fatty acid quantification, while related signaling pathways (EGFR, MAPK, AKT, and STAT3) were examined by Western blotting. The effects of G28 on LCSCs -including its impact on FASN and related signaling-were evaluated using the MTT assay and Western blotting.</p><p><strong>Results: </strong>LCSCs cultured in PCL-ES scaffolds showed a significant FASN upregulation, supporting their proliferation and maintenance. Despite reduced EGFR activation in 3D-cultured cells, downstream signaling responses differed: PC9 cells exhibited higher levels of p-AKT, p-MAPK, and p-STAT3, while PC9-GR3 cells showed reduced p-MAPK and p-AKT, with no changes in p-STAT3. Regarding G28 treatment, it exhibited cytotoxic effects in both 2D- and 3D-cultured cells, suggesting potential efficacy in targeting both non-LCSCs and LCSCs. Furthermore, the treatment downregulated FASN and AKT, reducing or avoiding the proliferation of this malignant population.</p><p><strong>Conclusion: </strong>Our results highlight the potential of G28 as a therapeutic option for targeting LCSCs in both sensitive and resistant EGFRm NSCLC cells, though additional studies are required to validate these results and assess their clinical applicability.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"57-72"},"PeriodicalIF":5.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199469","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":"LAURA Completes the Osimertinib Treatment Jigsaw Puzzle of <i>EGFR</i>+ NSCLC from Stage IB to IV: Adjuvant Osimertinib Significantly Improves PFS and CNS Progression in Unresectable Stage III <i>EGFR</i>-Mutated NSCLC Compared to Placebo (LAURA, NCT03521154).","authors":"Faustine X Luo, Zhaohui Arter, Sai-Hong Ignatius Ou, Misako Nagasaka","doi":"10.2147/LCTT.S520833","DOIUrl":"https://doi.org/10.2147/LCTT.S520833","url":null,"abstract":"<p><p>The current standard of care for unresectable stage III non-small cell lung cancer (NSCLC) involves a concurrent platinum-based doublet chemotherapy and chest radiotherapy, followed by consolidative therapy with durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, based on the PACIFIC trial (NCT02125461). However, the utility of durvalumab in <i>EGFR</i>-mutated lung cancer patients is questionable based on post-hoc analysis and multi-institutional retrospective analysis. Osimertinib is a third-generation <i>EGFR</i>-tyrosine kinase inhibitor (TKI) with proven clinical efficacy in NSCLC. Given that durvalumab showed no benefit in unresectable Stage III <i>EGFR</i>-mutated NSCLC, it is exciting that most recently, the LAURA trial has demonstrated promising outcomes with adjuvant osimertinib in unresectable, stage III <i>EGFR</i>-mutated NSCLC after definitive chemoradiotherapy with significant improvement in PFS compared to placebo. Furthermore, the LAURA trial demonstrates that osimertinib has a protective effect against distant metastases and CNS progression in this patient population. Here, we explore the results of the LAURA trial and how it transforms the standard-of-care treatment for patients with unresectable, stage III <i>EGFR</i>-mutated NSCLC moving forward.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"51-55"},"PeriodicalIF":5.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024412","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":"Prevalence of <i>EGFR</i> Mutations in Vietnamese Patients with Resected Early Stage Non-Small Cell Lung Cancer: EARLY-EGFR Study.","authors":"Tu Van Dao, Van Luong Dinh, Thanh Vinh Doan, Tri Le Phuong","doi":"10.2147/LCTT.S494554","DOIUrl":"https://doi.org/10.2147/LCTT.S494554","url":null,"abstract":"<p><strong>Introduction: </strong>Comprehensive profiling of mutations in the <i>EGFR</i> gene is vital for selecting patients eligible for <i>EGFR</i> targeted therapies.</p><p><strong>Methods: </strong>We investigated the prevalence of <i>EGFR</i> mutations and treatment patterns in patients with early stage non-small cell lung cancer (NSCLC) in Vietnam as a part of EARLY-EGFR (Clinical Trial Identifier: NCT04742192), a global, real-world study. Consecutive patients with surgically resected stage IA-IIIB, non-squamous NSCLC were diagnosed from August 2021 to June 2022 and were prospectively enrolled from November 2021 to July 2022.</p><p><strong>Results: </strong>A total 200 patients (age: median [range], 60.0 [30.0-80.0] years) were enrolled from 3 centers; 56.0% were males and 64.0% never smoked. The prevalence of <i>EGFR</i> mutations was 51.0% (102/200) including deletions in <i>exon-19</i> (49.0%) and <i>exon-21 L858R</i> mutations (33.3%). Females (73.9%, 65/88), patients aged ≥60 years (52.5%, 53/101), nonsmokers (61.2%, 63/103) and those with stage I (55.8%, 67/120) had higher prevalence of <i>EGFR</i> mutations. Multivariate analysis (adjusted odds ratio [aOR]) showed <i>EGFR</i> mutations to be significantly associated (p < 0.05) with female gender (aOR = 5.90), age ≥60 years (aOR = 1.05), and stage III disease (vs stage I) (aOR = 0.30).</p><p><strong>Conclusion: </strong>These results underscore the need for <i>EGFR</i> testing early in management algorithm of NSCLC in Vietnam to identify patients eligible for targeted therapy in concordance with international guidelines.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"39-49"},"PeriodicalIF":5.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064143","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":"Impact of Subsequent Treatment on Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Transformed to Small-Cell Lung Cancer.","authors":"Ching-Yi Chen, How-Wen Ko, Po-Wei Hu, Cheng-Yu Chang, Chung-Yu Chen, Shih-Chieh Chang, Yu-Chi Chiu, Yu-Feng Wei","doi":"10.2147/LCTT.S516527","DOIUrl":"https://doi.org/10.2147/LCTT.S516527","url":null,"abstract":"<p><strong>Purpose: </strong>In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs), transformation to small-cell lung cancer (SCLC) is associated with poor outcomes, and the optimal treatment strategy is unclear. This study aimed to investigate the clinical factors and treatments associated with outcomes in this group.</p><p><strong>Patients and methods: </strong>This retrospective multicenter study enrolled patients with SCLC transformed from advanced NSCLC after progression on EGFR-TKI treatment. We analyzed clinical and demographic characteristics, first-line EGFR-TKI treatments, and subsequent regimens to identify factors associated with clinical outcomes.</p><p><strong>Results: </strong>Twenty-seven patients diagnosed with SCLC transformation after EGFR-TKI therapy between 2018 and 2023 were enrolled, most of whom had an EGFR exon 19 deletion (67%). The subsequent treatment regimens included traditional chemotherapy (CT) in 12 patients (44%), combined CT/EGFR-TKI in 10 patients (37%), and combined CT/immunotherapy in 5 patients (19%). The median progression-free survival (PFS) with first-line EGFR-TKI treatment, subsequent SCLC treatment, and overall survival (OS) were 16.1 months, 6.4 months, and 39.5 months, respectively. The overall response rate (ORR), disease control rate (DCR), and median PFS for subsequent treatments were 38.5%, 69.2%, and 6.4 months, respectively. The DCRs for subsequent CT, CT/TKI, and CT/immunotherapy were 41.7%, 88.9%, and 100%, respectively. ORR and PFS were higher in the CT/TKI (44.4% and 7.2 months) and CT/immunotherapy (80.0% and 11.3 months) groups compared to CT (16.7% and 3.7 months), but these differences were not statistically significant. Univariate and multivariate analyses showed no significant differences in PFS and OS among treatments.</p><p><strong>Conclusion: </strong>In patients with SCLC transformed from advanced NSCLC after EGFR-TKI treatment, adding immunotherapy and EGFR-TKI to CT improved DCR and showed trends in ORR and PFS, but did not provide an OS benefit. More prospective studies with varied therapeutic approaches are needed to confirm these findings.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"25-37"},"PeriodicalIF":5.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064138","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":"Genomic Profiling of Extensive Stage Small-Cell Lung Cancer Patients Identifies Molecular Factors Associated with Survival.","authors":"Matteo Canale, Milena Urbini, Elisabetta Petracci, Davide Angeli, Gianluca Tedaldi, Ilaria Priano, Paola Cravero, Michele Flospergher, Kalliopi Andrikou, Chiara Bennati, Davide Tassinari, Alessandra Dubini, Giulio Rossi, Riccardo Panzacchi, Mirca Valli, Giuseppe Bronte, Lucio Crinò, Angelo Delmonte, Paola Ulivi","doi":"10.2147/LCTT.S492825","DOIUrl":"10.2147/LCTT.S492825","url":null,"abstract":"<p><strong>Objective: </strong>Extensive stage Small-Cell Lung Cancer (ES-SCLC) is the most lethal lung cancer, and the addition of immunotherapy conferred a slight survival benefit for patients. Extensive molecular profiling of patients treated with chemotherapy (CT) or chemotherapy plus immunotherapy (CT+IO) would be able to identify molecular factors associated with patients' survival.</p><p><strong>Material and methods: </strong>In this retrospective study, 99 ES-SCLC patients were considered. Of the 79 includible patients, 42 received CT (median age 71 y/o, I-IIIQ: 65-76), and 37 received CT+IO (median age 71 y/o, I-IIIQ 66-75). The FoundationOne CDx assay was performed on patients' tumor tissues.</p><p><strong>Results: </strong>The most mutated genes were <i>TP53</i> (99%), <i>RB1</i> (78%), <i>PTEN</i> (23%) and <i>MLL2</i> (20%), with no significant differences between the treatment groups. As a continuous variable, Tumor Mutation Burden (TMB) had an effect on patients' progression-free survival (PFS) by type of treatment (HR 1.81 (95%, CI: 0.99-3.31) and HR 0.84 (95%, CI: 0.56-1.26) for patients treated with CT and CT+IO, respectively). TMB was also computed and dichotomized using two different cut-offs: considering cut-offs of 10 mut/Mb and >16 mut/Mb, 45 patients (57%) and 68 patients (86.1%) had a low TMB, respectively. A high TMB (cut-off 10 mut/Mb) predicted worse PFS in patients treated with CT (<i>p</i>=0.046); even though not statistically significant, a high TMB (cut-off 16 mut/Mb) predicted a better survival in patients treated with CT+IO. Moreover, at univariate analysis, <i>MLL2</i> mutations were associated with better prognosis in the overall case series (HR_PFS = 0.51, 95% CI: 0.28-0.94), and overall survival (HR_OS = 0.52, 95% CI: 0.28-0.97).</p><p><strong>Conclusion: </strong>In ES-SCLC, TMB is associated with worse survival in patients treated with CT alone, and with better survival in patients treated with CT+IO, whether considered as a continuous or a dichotomized variable, at different cut-offs. Alterations in epigenetic factors are also associated to better patient prognosis.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"11-23"},"PeriodicalIF":5.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492641","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":"Comprehensive Survey of AACR GENIE Database of Tumor Mutation Burden (TMB) Among All Three Classes (I, II, III) of <i>BRAF</i> Mutated (<i>BRAF+</i>) NSCLC.","authors":"Zhaohui Liao Arter, Kevin Shieh, Misako Nagasaka, Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S493835","DOIUrl":"10.2147/LCTT.S493835","url":null,"abstract":"<p><strong>Background: </strong><i>BRAF</i> mutations are generally divided into three classes based on the different altered mechanism of activation.</p><p><strong>Methods: </strong>We queried the public AACR GENIE database (version 13.1), which includes tumor mutation burden (TMB) data, to explore potential molecular differences among the three classes of non-small cell lung cancer (NSCLC).</p><p><strong>Results: </strong>Out of 20,713 unique NSCLC patients, 324 (1.6%) were <i>BRAF</i> mutations positive <i>(BRAF</i>+) class I, 260 (1.3%) class II, and 236 (1.1%) class III. The distribution of patient characteristics, including sex, age, and race, remains uniform across the three classes. The median TMB (mt/MB) was 6.5, 9.5, and 10.3 for class I, II, and III, respectively. The mean TMB was 61.5 ± 366.1 for class I, 40.5 ± 156.2 for class II, and 129.4 ± 914.8 for class III. About 30.5% of <i>BRAF</i> V600E+ patients had TMB ≥ 10; 47.7% of class II had TMB ≥ 10; and 52.5% of class III had TMB ≥ 10. For those patients with TMB ≥ 10, the median TMB was 45, 28.9, 18.4 for class I, II, and III, respectively. For TMB ≥ 10 patients, <i>TP53</i> mutation was the most common co-alterations across all 3 classes.</p><p><strong>Conclusion: </strong>A substantial proportion of <i>BRAF</i>+ NSCLC patients exhibited a TMB ≥ 10, among all three classes of <i>BRAF</i> mutation classification, including <i>BRAF</i> V600E+ NSCLC. Class III mutations appeared to have the highest median TMB, followed by class II, and then class I.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"1-9"},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492654","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":"Adagrasib in KRYSTAL-12 has Not Broken the KRAS G12C Enigma Code of the Unspoken 6-Month PFS Barrier in NSCLC.","authors":"Alexandria T M Lee, Misako Nagasaka","doi":"10.2147/LCTT.S492126","DOIUrl":"10.2147/LCTT.S492126","url":null,"abstract":"<p><p>Mutations in KRAS G12C are among the more common oncogenic driver mutations in non-small cell lung cancer (NSCLC). In December 2022, the US Food and Drug Administration (FDA) granted accelerated approval to adagrasib, a small molecule covalent inhibitor of KRAS G12C, for the treatment of patients with locally advanced or metastatic KRAS G12C mutant NSCLC who received at least one prior systemic therapy based on promising results from phase 1 and 2 trials wherein adagrasib demonstrated a median PFS of 6.5 months. Results from the phase 3 KRYSTAL-12 trial were recently presented, showing benefit with adagrasib compared to docetaxel, with participants in the adagrasib group demonstrating a PFS of 5.5 months compared to 3.8 months in the docetaxel group. However, these results fall short of the 6-month PFS benchmark that had seemed achievable from what had been seen in phase 1 and 2 trials, mirroring similarly disappointing results from the CodeBreaK 200 trial wherein sotorasib, the first-in-class KRAS G12C inhibitor, also failed to meet the 6-month benchmark also thought to be possible when examining earlier trials. These results raise the question of adagrasib's true value in the second-line treatment setting and compel us to explore more potent novel therapies, combination therapies, and more as we seek to break the 6-month PFS barrier in the treatment of KRAS G12C mutant NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"169-176"},"PeriodicalIF":5.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882356","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":"Adagrasib in KRYSTAL-12 has Broken the <i>KRAS</i> ^G12C Enigma Code in Non-Small Cell Lung Carcinoma.","authors":"Faustine X Luo, Zhaohui Liao Arter","doi":"10.2147/LCTT.S490942","DOIUrl":"10.2147/LCTT.S490942","url":null,"abstract":"<p><p>Kirsten rat sarcoma viral oncogene homolog <i>(KRAS)</i> ^G12C-mutant non-small cell lung carcinoma (NSCLC) accounts for approximately 10-13% of advanced nonsquamous NSCLC cases in Western populations, presenting a significant therapeutic challenge owing to the difficulty of directly targeting KRAS. Adagrasib, an oral small-molecule covalent inhibitor, irreversibly and selectively targets KRAS^G12C in its inactive state. It received accelerated Food and Drug Administration (FDA) approval on December 12, 2022, following the KRYSTAL-1 Phase II trial. The Phase III KRYSTAL-12 trial demonstrated that adagrasib significantly improved median progression-free survival (mPFS) compared with docetaxel (HR, 0.58; 95% CI: 0.45-0.76; P<0.0001) and increased the intracranial objective response rate (ORR) to 40% in the central nervous system (CNS) evaluable population. This paper evaluates the clinical efficacy of adagrasib in <i>KRAS</i> ^G12C-mutated advanced NSCLC discussing its potential advantages over other inhibitors such as sotorasib. Despite not reaching the 6-month mPFS benchmark, adagrasib offers significant clinical benefits, particularly for the management of CNS metastases. In this pros and cons debate, we argue that adagrasib has broken the <i>KRAS</i> ^G12C enigma code in NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"161-167"},"PeriodicalIF":5.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582857","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":"Real-World Outcomes with Lurbinectedin in Second Line and Beyond for Extensive Stage Small Cell Lung Cancer in Korea.","authors":"Joo Sung Shim, Youhyun Kim, Taeho Yuh, Jii Bum Lee, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim","doi":"10.2147/LCTT.S485320","DOIUrl":"10.2147/LCTT.S485320","url":null,"abstract":"<p><strong>Purpose: </strong>Small-cell lung cancer (SCLC) accounts for approximately 10-15% of all lung cancers and is characterized by a high recurrence rate, early metastasis, and poor prognosis. Before the FDA approved lurbinectedin for SCLC that progressed on or after platinum-based chemotherapy in 2020, topotecan was the sole second-line option associated with hematological toxicities and modest efficacy. Lurbinectedin received conditional approval in Korea in September 2022 for metastatic SCLC progression, with the same indications. Real-world data on its efficacy remains scarce owing to its recent implementation.</p><p><strong>Patients and methods: </strong>Patients with metastatic SCLC who progressed on or after first-line therapy (n = 51) at Yonsei Cancer Center, Seoul, received lurbinectedin at 3.2 mg/m². Efficacy data, including tumor response, progression, survival, and demographics, were recorded.</p><p><strong>Results: </strong>A total of fifty-one patients received lurbinectedin between April 2023 and March 2024, with thirty-four patients being eligible for the assessment. At diagnosis, approximately one-third of the patients were female, 3% had a poor performance status with an Eastern Cooperative Oncology Group Performance Score (ECOG PS ≥ 2), and the median age was 68. Most patients (80%) had extensive disease. Overall objective response rate (ORR) and disease control rate (DCR) were 20% and 47%, respectively. The median progression-free survival (PFS) was 2.8 months, and the median overall survival (OS) was 3.3 months. Never smokers showed prolonged OS compared with current/former smokers (Smokers; 3.0 vs 7.3 months). Common adverse effects were nausea (53%), loss of appetite (24%), general weakness (18%), anemia (29%), neutropenia (12%), dizziness (6%), alopecia (6%), thrombocytopenia (3%), and pneumonia (3%). Overall, 24% of the patients experienced grade ≥3 adverse events (AEs), with the most common being anemia (9%) and neutropenia (9%).</p><p><strong>Conclusion: </strong>Real-world data suggest that lurbinectedin is a viable option for patients with SCLC who have progressed on or after platinum-based chemotherapy.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"149-159"},"PeriodicalIF":5.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567432","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}