Targeted Oncology最新文献

{"title":"Evaluation of Drug–Drug Interaction Potential of Talquetamab, a T-Cell-Redirecting GPRC5D × CD3 Bispecific Antibody, as a Result of Cytokine Release Syndrome in Patients with Relapsed/Refractory Multiple Myeloma in MonumenTAL-1, Using a Physiologically Based Pharmacokinetic Model","authors":"Marie-Emilie Willemin, Jue Gong, Brandi W. Hilder, Tara Masterson, Jaszianne Tolbert, Thomas Renaud, Christoph Heuck, Colleen Kane, Loeckie De Zwart, Suzette Girgis, Xuewen Ma, Daniele Ouellet","doi":"10.1007/s11523-024-01093-6","DOIUrl":"https://doi.org/10.1007/s11523-024-01093-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Cytokine release syndrome, commonly associated with T-cell immunotherapies, was observed with talquetamab, a T-cell-redirecting bispecific antibody, in the phase I/II MonumenTAL-1 study, leading to elevated interleukin (IL)-6, which can suppress cytochrome P450 (CYP) enzyme activity.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>We aimed to evaluate the potential impact of elevated IL-6 on the exposure of co-administered CYP450 substrates for two scenarios: (1) the observed median IL-6 profile and (2) a profile with the highest IL-6 maximum concentration following talquetamab treatment.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A physiologically based pharmacokinetic model was developed based on the literature and simulations performed using observed IL-6 profiles from patients in MonumenTAL-1 who received the subcutaneous recommended phase 2 doses (RP2Ds) of talquetamab: 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Median IL-6 maximum concentration was 18.4 and 7.1 pg/mL, and maximum IL-6 maximum concentration was 213 and 3503 pg/mL for talquetamab QW and Q2W RP2Ds, respectively. For the median IL-6 profile, no interaction between IL-6 and studied CYP substrates was predicted at either RP2D. The maximum IL-6 profile predicted weak-to-moderate impact on exposure of CYP2C19, CYP3A4, and CYP3A5 substrates and minimal impact on exposure of CYP1A2 substrates at both RP2Ds. Impact on exposure of CYP2C9 substrates was predicted as minimal at QW and minimal-to-weak at Q2W RP2Ds. Time to return to 20% difference from baseline enzymatic activity was predicted as 7 and 9 days after start of cycle 1 for QW and Q2W RP2Ds, respectively.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These modeling results suggest that IL-6 release due to talquetamab-induced cytokine release syndrome has limited impact on potential drug–drug interactions, with the highest likelihood of impact occurring from initiation of talquetamab step-up dosing up to 7 (QW) or 9 (Q2W) days after first treatment dose in cycle 1 and during and after cytokine release syndrome.</p><h3 data-test=\"abstract-sub-heading\">Plain Language Summary</h3><p>Multiple myeloma can be treated with immunotherapies such as the bispecific antibody, talquetamab, which binds the novel antigen G protein-coupled receptor family C group 5 member D on multiple myeloma cells and CD3 on T cells and induces T-cell-mediated lysis of multiple myeloma cells. Following talquetamab treatment, many patients experience cytokine release syndrome, an inflammatory immune response where levels of proinflammatory cytokines, including interleukin (IL)-6, are increased. Interleukin-6 can suppress the activity of important enzymes in the body (cytochrome [CYP] P450s) that are involved in drug clearance. This study used a physiologically based pharmacokinetic computer model to i","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffuse Gastric Cancer: A Comprehensive Review of Molecular Features and Emerging Therapeutics","authors":"Lawrence W. Wu, Sung Joo Jang, Cameron Shapiro, Ladan Fazlollahi, Timothy C. Wang, Sandra W. Ryeom, Ryan H. Moy","doi":"10.1007/s11523-024-01097-2","DOIUrl":"https://doi.org/10.1007/s11523-024-01097-2","url":null,"abstract":"<p>Diffuse-type gastric cancer (DGC) accounts for approximately one-third of gastric cancer diagnoses but is a more clinically aggressive disease with peritoneal metastases and inferior survival compared with intestinal-type gastric cancer (IGC). The understanding of the pathogenesis of DGC has been relatively limited until recently. Multiomic studies, particularly by The Cancer Genome Atlas, have better characterized gastric adenocarcinoma into molecular subtypes. DGC has unique molecular features, including alterations in <i>CDH1</i>, <i>RHOA</i>, and <i>CLDN18-ARHGAP26</i> fusions. Preclinical models of DGC characterized by these molecular alterations have generated insight into mechanisms of pathogenesis and signaling pathway abnormalities. The currently approved therapies for treatment of gastric cancer generally provide less clinical benefit in patients with DGC. Based on recent phase II/III clinical trials, there is excitement surrounding Claudin 18.2-based and FGFR2b-directed therapies, which capitalize on unique biomarkers that are enriched in the DGC populations. There are numerous therapies targeting Claudin 18.2 and FGFR2b in various stages of preclinical and clinical development. Additionally, there have been preclinical advancements in exploiting unique therapeutic vulnerabilities in several models of DGC through targeting of the focal adhesion kinase (FAK) and Hippo pathways. These preclinical and clinical advancements represent a promising future for the treatment of DGC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan.","authors":"Dirk J A R Moes, Jeroen J M A Hendrikx, Henk-Jan Guchelaar, Ron H J Mathijssen, J L Bakker, Vincent O Dezentjé, Nikki de Rouw, Nielka P van Erp, Egbert F Smit, Michel M van den Heuvel, Thijs H Oude Munnink, Maartje van Kats, Sander Croes, Judith R Kroep, Juliette Zwaveling, Rob Ter Heine","doi":"10.1007/s11523-024-01075-8","DOIUrl":"10.1007/s11523-024-01075-8","url":null,"abstract":"<p><strong>Background: </strong>The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality.</p><p><strong>Objective: </strong>The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access.</p><p><strong>Patients and methods: </strong>Exposure equivalent dosing strategies were developed based on pharmacokinetic modeling and simulation by using the published pharmacokinetic model developed by the license holder. The alternative dose was based on the principle of using complete vials to prevent spillage and on the established non-linear relationship between body weight and systemic exposure. Equivalent exposure compared to the approved dosing regimen of 10 mg/kg was aimed for. Equivalent exposure was conservatively defined as calculated geometric mean ratios within the 0.9-1.11 boundaries for area under the concentration-time curve (AUC), trough concentration (C_trough) and maximum concentration (C_max) of the alternative dosing regimen compared to the approved dosing regimen. Since different vial sizes are available for the European Union (EU) and United States (US) market, because body weight distributions differ between these populations, we performed our analysis for both scenarios.</p><p><strong>Results: </strong>Dosing regimens of sacituzumab govitecan for the EU (< 50 kg: 400 mg, 50-80 kg: 600 mg, and > 80 kg: 800 mg) and US population (< 40 kg: 360 mg, 40-65 kg: 540 mg, 65-90 kg: 720 mg, and > 90 kg: 900 mg) were developed, based on weight bands. The geometric mean ratios for all pharmacokinetic outcomes were within the predefined equivalence boundaries, while the quantity of drug used was 21.5% and 19.0% lower for the EU and US scenarios, respectively.</p><p><strong>Conclusions: </strong>With the alternative dosing proposal, an approximately 20% reduction in drug expenses for sacituzumab govitecan can be realized while maintaining an equivalent and more evenly distributed exposure throughout the body weight range, without notable increases in pharmacokinetic variability.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Moving T‑Cell Therapies into the Standard of Care for Patients with Relapsed or Refractory Follicular Lymphoma: A Review.","authors":"Nathan Hale Fowler, Julio C Chavez, Peter A Riedell","doi":"10.1007/s11523-024-01085-6","DOIUrl":"10.1007/s11523-024-01085-6","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.","authors":"Mart P Kicken, Maarten J Deenen, Dirk J A R Moes, Jeroen J M A Hendrikx, Ben E E M van den Borne, Daphne W Dumoulin, Anthonie J van der Wekken, Michiel M van den Heuvel, Rob Ter Heine","doi":"10.1007/s11523-024-01087-4","DOIUrl":"10.1007/s11523-024-01087-4","url":null,"abstract":"<p><strong>Background: </strong>Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase.</p><p><strong>Objective: </strong>We propose two alternative dosing regimens for subcutaneous atezolizumab to reduce drug expenses while ensuring effective exposure; one may be directly implemented in the clinic.</p><p><strong>Patients and methods: </strong>We developed two alternative dose interval prolongation strategies based on pharmacokinetic modeling and simulation. The first dosing regimen was based on patients' weight while maintaining equivalent systemic drug exposure by adhering to Food and Drug Administration (FDA) guidelines for in silico dose adjustments. The second dosing regimen aimed to have a minimum atezolizumab concentration above the 6 µg/mL threshold, associated with 95% intratumoral PD-L1 receptor saturation for at least 95% of all patients.</p><p><strong>Results: </strong>We found that, for the weight-based dosing regimen, the approved 3-week dosing interval could be extended to 5 weeks for patients < 50 kg and 4 weeks for patients weighing 50-65 kg. Besides improving patient convenience, these alternative dosing intervals led to a predicted 7% and 12% cost reduction for either the USA or European population. For the second dosing regimen, we predicted that a 6-week dosing interval would result in 95% of the patients above the 6 µg/mL threshold while reducing costs by 50%.</p><p><strong>Conclusions: </strong>We have developed and evaluated two alternative dosing regimens that resulted in a cost reduction. Our weight-based dosing regimen can be directly implemented and complies with FDA guidelines for alternative dosing regimens of PD-L1 inhibitors. For the more progressive alternative dosing regimen aimed at the intratumoral PD-L1 receptor threshold, further evidence on efficacy and safety is needed before implementation.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"lnsights into Adjuvant Systemic Treatment Selection for Patients with Stage III Melanoma: Data from the Dutch Cancer Registry.","authors":"Loeki Aldenhoven, Merel A Spiekerman van Weezelenburg, Franchette W P J van den Berkmortel, Nick Servaas, Alfred Janssen, Yvonne L J Vissers, Elisabeth R M van Haaren, Geerard L Beets, James van Bastelaar","doi":"10.1007/s11523-024-01090-9","DOIUrl":"10.1007/s11523-024-01090-9","url":null,"abstract":"<p><strong>Background: </strong>Patient demographics and shared decision making might influence the choice of adjuvant therapy for stage III melanoma.</p><p><strong>Objective: </strong>To identify factors for treatment selection of patients diagnosed with stage III melanoma to better understand current treatment decisions and improve further treatment counseling.</p><p><strong>Patients and methods: </strong>Data from 2007 patients diagnosed with stage III melanoma, between December 2018 and 2021, sourced from the Dutch Cancer Registry, were analyzed.</p><p><strong>Results: </strong>Among the cohort, 48.7% received no therapy, 45.8% received checkpoint inhibition, and 5.5% received targeted therapy (TT). Patients foregoing therapy were significantly older [67.0 years (range 53.0-77.0) vs. 62.0 year (range 52.0-72.0)], had poorer performance scores (PS), and higher Charlson Comorbidity Index scores compared to those receiving therapy (p < 0.001). Patients undergoing therapy had significantly higher median Breslow thickness (3.3 mm vs. 2.2 mm) and higher prevalence of ulceration (49.9% vs. 38.1%). Those with connective tissue disease and/or congestive heart disease were more likely to receive TT [odds ration (OR) 8.1; 95% confidence interval (CI) 1.7-37.6 and OR 9.3; 95% CI 1.2-72.2, respectively]. Median treatment time among strata for disease recurrence was 4.26 months (3.69-4.82) for immunotherapy and 3.1 months (0.85-5.36) for TT (p = 0.298). Patients who developed recurrent disease were equal across treatment types (p = 0.656). The number of patients with grade 3 complications was different for each treatment type [immunotherapy: 17.8% vs. TT: 37.3% (p < 0.001)].</p><p><strong>Conclusions: </strong>Age, PS, and Breslow thickness seem to influence adjuvant treatment decisions. Clinicians' preference for immunotherapy might play a role in counseling BRAF-positive patients for adjuvant therapy, this however, cannot be confirmed in this dataset. Overall, only a small proportion of patients completed adjuvant treatment.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Actionable Alterations in KRAS Wild-Type Pancreatic Cancer.","authors":"Ahmed Elhariri, Jaydeepbhai Patel, Himil Mahadevia, Douaa Albelal, Ahmed K Ahmed, Jeremy C Jones, Mitesh J Borad, Hani Babiker","doi":"10.1007/s11523-024-01088-3","DOIUrl":"10.1007/s11523-024-01088-3","url":null,"abstract":"<p><p>The 5-year relative survival rate for pancreatic cancer is currently the lowest among all cancer types with a dismal 13%. A Kirsten rat sarcoma virus (KRAS) gene mutation is present in approximately 90% of patients with pancreatic cancer; however, KRAS-specific drugs are not yet widely used in clinical practice for pancreatic cancer, specifically the KRAS^G12D variant. Advances in genomic testing revealed an opportunity to detect genetic alterations in a subset of patients with no KRAS mutation termed KRAS wild-type. Patients with KRAS wild-type tumors have a propensity to express driver alterations, hence paving the way for utilizing a targeted therapy approach either via clinical trials or standard-of-care drugs. These alterations include fusions, amplifications, translocations, rearrangements and microsatellite instability-high tumors and can be as high as 11% in some studies. Here, we discuss some of the most notable alterations in KRAS wild-type and highlight promising clinical trials.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma.","authors":"Jifang Gong, Ye Guo, Yanqiao Zhang, Yi Ba, Tong Chen, Wei Li, Caicun Zhou, Mengzhao Wang, Haiyan Yang, Yuhong Zhou, Qiqing Cai, Ziping Wang, Gang Huang, Wei Zhang, Rila Su, Zhongheng Cai, Zenglian Yue, Jinzhou Dou, Peiqi Li, Rachel Wu, Archie N Tse, Lin Shen","doi":"10.1007/s11523-024-01091-8","DOIUrl":"10.1007/s11523-024-01091-8","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies has demonstrated efficacy in multiple tumor types. Nofazinlimab is a humanized rat antibody targeting PD-1. A first-in-human study of nofazinlimab conducted in Australia found no dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) was not reached in the range of 1-10 mg/kg.</p><p><strong>Objective: </strong>We evaluated nofazinlimab for multiple advanced malignancies in Chinese patients.</p><p><strong>Patients and methods: </strong>This was a phase 1a/1b, open-label, multicenter, dose-escalation/expansion trial. In phase 1a, patients received an abbreviated dose escalation of nofazinlimab at 60 mg and 200 mg every 3 weeks (Q3W) to determine DLTs and the recommended phase 2 dose (RP2D). In phase 1b, patients received the RP2D (monotherapy/combination) in six arms by tumor type; DLTs were evaluated for nofazinlimab plus lenvatinib in the unresectable hepatocellular carcinoma (uHCC) arm. Safety (continuously monitored in patients who received nofazinlimab) and efficacy (patients with measurable baseline disease) were assessed.</p><p><strong>Results: </strong>Overall, 107 patients were eligible and received nofazinlimab. In phase 1a, no DLTs were observed; the RP2D was 200mg Q3W. In phase 1b, no DLTs were observed with nofazinlimab plus lenvatinib. The safety profile was consistent with that observed in the first-in-human study (NCT03475251). In phase 1b, 21/88 (23.9%) patients achieved confirmed objective responses, 26 (29.5%) had stable disease, and 9/20 (45.0%) patients with uHCC achieved confirmed objective responses to nofazinlimab plus lenvatinib.</p><p><strong>Conclusions: </strong>Nofazinlimab was well tolerated in Chinese patients. Preliminary efficacy was encouraging, particularly for nofazinlimab plus lenvatinib in uHCC, which is being studied in an ongoing phase 3 trial.</p><p><strong>Clinical trial registration: </strong>NCT03809767; registered 18 January 2019.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: \"Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta‑analysis\".","authors":"Jun Ma, Wei Han","doi":"10.1007/s11523-024-01082-9","DOIUrl":"10.1007/s11523-024-01082-9","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Stratification According to Baseline and Early Change in Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Treated with Chemoimmunotherapy: A Multicenter Real-World Study.","authors":"Kinnosuke Matsumoto, Yuji Yamamoto, Takayuki Shiroyama, Tomoki Kuge, Masahide Mori, Motohiro Tamiya, Yuhei Kinehara, Akihiro Tamiya, Hidekazu Suzuki, Satoshi Tobita, Kiyonobu Ueno, Toshie Niki, Izumi Nagatomo, Yoshito Takeda, Atsushi Kumanogoh","doi":"10.1007/s11523-024-01084-7","DOIUrl":"10.1007/s11523-024-01084-7","url":null,"abstract":"<p><strong>Background: </strong>Chemoimmunotherapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, data on clinical predictive factors remain scarce.</p><p><strong>Objective: </strong>We aim to identify clinical biomarkers in patients undergoing chemoimmunotherapy.</p><p><strong>Methods: </strong>This multicenter, real-world cohort study included chemonaive patients who underwent chemoimmunotherapy between December 2018 and May 2022. Multivariate analysis was used to determine associations between survival outcomes and patient background, including baseline neutrophil-to-lymphocyte ratio (NLR) and its dynamic change (ΔNLR). To further investigate the clinical significance of NLR, patients were classified based on their peripheral immune status, defined by a combination of NLR and ΔNLR.</p><p><strong>Results: </strong>The study included 280 patients with 30.1 months of median follow-up. Multivariate analysis revealed that older individuals, poor performance status, tumor proportion score < 1%, liver metastasis, baseline NLR ≥ 5, and ΔNLR ≥ 0 independently correlated significantly with shorter progression-free and overall survival (OS). Patients with high peripheral immune status (defined as NLR <5 and ΔNLR < 0) significantly improved long-term survival (2-year OS rate of 58.3%), whereas those with low peripheral immune status (defined as NLR ≥ 5 and ΔNLR ≥ 0) had extremely poor outcomes (2-year OS rate of 5.6%). Safety profiles did not differ significantly in terms of severe adverse events and treatment-related death rates despite the patients' peripheral immune status (P = 0.46 and 0.63, respectively).</p><p><strong>Conclusions: </strong>Our study provides real-world evidence regarding clinical prognostic factors for the efficacy of chemoimmunotherapy. The combined assessment of baseline NLR and ΔNLR could facilitate the identification of patients who are likely to achieve a durable response from chemoimmunotherapy.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}