Targeted Oncology最新文献

{"title":"Trastuzumab-Deruxtecan: Redefining HER2 as a Tumor Agnostic Biomarker.","authors":"Joseph Zouein, Elias Karam, John H Strickler, Hampig Raphael Kourie","doi":"10.1007/s11523-024-01079-4","DOIUrl":"10.1007/s11523-024-01079-4","url":null,"abstract":"<p><p>Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) targeting HER2-positive malignancies across various tumor types. Through its unique composition, T-DXd achieves selective payload delivery, inducing cell death and halting tumor progression. Clinical trials initially investigated T-DXd's efficacy in HER2-positive advanced or metastatic breast, gastric, lung, and colorectal cancers; however, recent results from the DESTINY-PanTumor02 trial further underscore T-DXd's versatility, prompting T-DXd's US FDA approval for HER2-positive (immunohistochemistry [IHC] 3+) solid tumors. Moreover, in addition to T-DXd's efficacy against brain metastasis, T-DXd is showing promising results in HER2-low and HER2-ultra-low metastatic breast cancer, indicating a broader population of patients who may benefit.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"705-710"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499057","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":"Author's Reply to Ma et al.: \"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":"Brigida Anna Maiorano, Andrea Necchi, Massimo Di Maio","doi":"10.1007/s11523-024-01083-8","DOIUrl":"10.1007/s11523-024-01083-8","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"813-815"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724566","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":"Patient Enrollment per Month (Accrual) in Clinical Trials Leading to the FDA Approval of New Cancer Drugs.","authors":"Daniel Tobias Michaeli, Thomas Michaeli, Sebastian Albers, Julia Caroline Michaeli","doi":"10.1007/s11523-024-01081-w","DOIUrl":"10.1007/s11523-024-01081-w","url":null,"abstract":"<p><strong>Background: </strong>Insufficient patient enrollment per month (=accrual) is the leading cause of cancer trial termination.</p><p><strong>Objective: </strong>To identify and quantify factors associated with patient accrual in trials leading to the US Food and Drug Administration (FDA) approval of new cancer drugs.</p><p><strong>Data: </strong>All anti-cancer drugs with FDA approval were identified in the Drugs@FDA database (2000-2022). Data on drug indication's background-, treatment-, disease-, and trial-related factors were collected from FDA labels, clinicaltrials.gov, and the Global Burden of Disease study. The association between patient accrual and collected variables was assessed in Poisson regression models reporting adjusted rate ratios (aRR).</p><p><strong>Results: </strong>We identified 170 drugs with approval in 455 cancer indications on the basis of 292 randomized and 163 single-arm trials. Among randomized trials, median enrollment per month was 38 patients (interquartile range [IQR]: 26-54) for non-orphan, 21 (IQR: 15-38, aRR 0.88, p = 0.361) for common orphan, 20 (IQR: 10-35, aRR 0.73, p <0.001) for rare orphan, and 8 (IQR 6-12, aRR 0.30, p < 0.001) for ultra-rare orphan indications. Patient enrollment was positively associated with disease burden [aRR: 1.0003 per disability-adjusted life year (DALY), p < 0.001), trial sites (aRR: 1.001 per site, p < 0.001), participating countries (aRR: 1.02 per country, p < 0.001), and phase 3 vs. 1/2 trials (aRR: 1.64, p = 0.037). Enrollment was negatively associated with advanced-line vs. first-line treatments (aRR: 0.81, p = 0.010) and monotherapy vs. combination treatments (aRR: 0.80, p = 0.007). Patient enrollment per month was similar between indications with and without a biomarker (median: 27 vs. 32, aRR 0.80, p = 0.117). Patient enrollment per month was substantially lower in government-sponsored than industry-sponsored trials (median: 14 vs. 32, aRR 0.80, p = 0.209). Enrollment was not associated with randomization ratios, crossover, and study blinding.</p><p><strong>Conclusions: </strong>Disease incidence and disease burden alongside the number of study sites and participating countries are the main drivers of patient enrollment in clinical trials. For rare disease trials, greater financial incentives could help expedite patient enrollment. Novel trial design features, including skewed randomization, crossover, or open-label masking, did not entice patient enrollment.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"797-809"},"PeriodicalIF":4.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861029","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":"Survival Impact of Glucocorticoid Administration for Adverse Events During Immune Checkpoint Inhibitor Combination Therapy in Patients with Previously Untreated Advanced Renal Cell Carcinoma.","authors":"Maki Yoshino, Hiroki Ishihara, Yuki Nemoto, Shinsuke Mizoguchi, Takashi Ikeda, Takayuki Nakayama, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka, Hiroaki Shimmura, Yasunobu Hashimoto, Tsunenori Kondo, Toshio Takagi","doi":"10.1007/s11523-024-01069-6","DOIUrl":"10.1007/s11523-024-01069-6","url":null,"abstract":"<p><strong>Background: </strong>The impact of glucocorticoid administration for adverse events (AEs), including immune-related AEs, on the effectiveness of immune checkpoint inhibitor (ICI) combination therapy for advanced renal cell carcinoma (RCC) remains unknown.</p><p><strong>Objectives: </strong>To clarify the prognostic impact of glucocorticoid use for AEs during first-line ICI combination therapy for advanced RCC.</p><p><strong>Patients and methods: </strong>We retrospectively evaluated data from 194 patients who received dual ICI combination therapy [i.e., immunotherapy (IO)-IO] or combinations of ICIs with tyrosine kinase inhibitors (TKIs) as first-line therapy. The patients were divided into two groups according to the history of glucocorticoid administration in each treatment group. Survival based on glucocorticoid administration was assessed.</p><p><strong>Results: </strong>A total of 101 (52.0%) and 93 (48.0%) patients received IO-IO and IO-TKI combination therapy, respectively. Glucocorticoids were administered to 46 (46%) and 22 (24%) patients in the IO-IO and IO-TKI groups, respectively. In the IO-IO group, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with glucocorticoid administration than in those without administration (median PFS: 14.4 versus 3.45 months, p = 0.0005; median OS: 77.6 versus 33.9 months, p = 0.0025). Multivariable analysis showed that glucocorticoid administration was an independent predictor of longer PFS (hazard ratio: 0.43, p = 0.0005) and OS (hazard ratio: 0.35, p = 0.0067) after adjustment for covariates. In the IO-TKI group, neither PFS nor OS significantly differed between patients treated with and without glucocorticoid administration (PFS: p = 0.0872, OS: p = 0.216).</p><p><strong>Conclusions: </strong>Glucocorticoid administration did not negatively impact the effectiveness of ICI combination therapy for RCC, prompting glucocorticoid treatment use when AEs develop.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"623-633"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180658","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":"Impact of PD-L1 Expression on the Overall Survival of Caucasian Patients with Advanced EGFR-Mutant NSCLC Treated with Frontline Osimertinib.","authors":"Thomas Papazyan, Marc G Denis, Christine Sagan, Judith Raimbourg, Guillaume Herbreteau, Elvire Pons-Tostivint","doi":"10.1007/s11523-024-01072-x","DOIUrl":"10.1007/s11523-024-01072-x","url":null,"abstract":"<p><strong>Background: </strong>The treatment of advanced non-small cell lung cancer (NSCLC) harboring an oncogenic epidermal growth factor receptor mutation (EGFRm) is currently based on osimertinib, a third-generation tyrosine kinase inhibitor (TKI). High Programmed death ligand 1 (PD-L1) expression ≥ 50% demonstrated to be a negative prognostic factor, mostly among Asian populations treated with 1st/2nd generation TKI.</p><p><strong>Objective: </strong>We investigated the impact of PD-L1 expression on the progression free survival (PFS) and overall survival (OS) within a cohort of patients receiving osimertinib as first-line treatment.</p><p><strong>Methods: </strong>Our bi-centre French retrospective study included all newly diagnosed patients with an advanced EGFRm (common and uncommon) NSCLC, between May 2018 and November 2022, treated with osimertinib. The primary endpoint was OS according to tumor proportion score PD-L1 expression (low/intermediate < 50% vs high ≥ 50%). Survival analyses were performed using Kaplan-Meier method and Cox model for adjusted multivariate analysis.</p><p><strong>Results: </strong>Of 96 patients, median age was 71 (IQR 62-76), 70 were women (72.9%), 81 had a performance status (PS) 0-1 (84.3%). Median follow-up was 22.6 months (95% CI 20.5-24.7). Twenty patients (20.8%) had high PD-L1 expression ≥ 50%. No significant differences in baseline characteristics were observed based on PD-L1 status. Patients with PD-L1 ≥ 50% had significant shorter PFS and OS than those with PD-L1 < 50%, respectively 9.3 vs 17.5 months (p = 0.044 months) and 14.3 vs 26.0 months (p = 0.025). Multivariable adjustment for baseline characteristics found that PS ≥ 2 (HR 2.79, 95% CI 1.12-6.93, p = 0.027), PD-L1 ≥ 50% (HR 2.61, 95% CI 1.31 to 5.22, p = 0.007) and uncommon EGFR mutation (HR 4.59, 95% CI 1.95-10.80, p = <0.001) were associated with a shorter OS. Brain metastases at diagnosis and age ≥ 65 were not, respectively HR 1.66 (95% CI 0.90-3.06, p = 0.11) and HR 0.95 (95% CI 0.50-1.80, p=0.9).</p><p><strong>Conclusions: </strong>Our study found that PD-L1 expression ≥ 50% was associated with a shorter OS in EGFRm NSCLC patients treated with first line osimertinib. Further research is warranted to understand the underlying molecular and cellular mechanisms of this correlation.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"611-621"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200606","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: \"Prognostic and Predictive Value of PIK3CA Mutations in Metastatic Colorectal Cancer\".","authors":"Wei Han, Yong-Wei Hu, Wei-Jie Lu, Hao-Nan Wang","doi":"10.1007/s11523-024-01066-9","DOIUrl":"10.1007/s11523-024-01066-9","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"661-662"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238245","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":"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/s11523-024-01070-z","DOIUrl":"10.1007/s11523-024-01070-z","url":null,"abstract":"<p><p>Patients with follicular lymphoma, an indolent form of non-Hodgkin lymphoma, typically experience multiple relapses over their disease course. Periods of remission become progressively shorter with worse clinical outcomes after each subsequent line of therapy. Currently, no clear standard of care/preferred treatment approach exists for patients with relapsed or refractory follicular lymphoma. As novel agents continue to emerge for treatment in the third-line setting, guidance is needed for selecting the most appropriate therapy for each patient. Several classes of targeted therapeutic agents, including monoclonal antibodies, phosphoinositide 3-kinase inhibitors, enhancer of zeste homolog 2 inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and bispecific antibodies, have been approved by regulatory authorities based on clinical benefit in patients with relapsed or refractory follicular lymphoma. Additionally, antibody-drug conjugates and other immunocellular therapies are being evaluated in this setting. Effective integration of CAR-T cell therapy into the treatment paradigm after two or more prior therapies requires appropriate patient selection based on transformation status following a rebiopsy; a risk evaluation based on age, fitness, and remission length; and eligibility for CAR-T cell therapy. Consideration of important logistical factors (e.g., proximity to the treatment center and caregiver support during key periods of CAR-T cell therapy) is also critical. Overall, an individualized treatment plan that considers patient-related factors (e.g., age, disease status, tumor burden, comorbidities) and prior treatment types is recommended for patients with relapsed or refractory follicular lymphoma. Future analyses of real-world data and a better understanding of mechanisms of relapse are needed to further refine patient selection and identify optimal sequencing of therapies in this setting.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"495-510"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421077","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":"C-Reactive Protein-Albumin Ratio Predicts Objective Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma.","authors":"Taizo Uchimoto, Takuya Matsuda, Kazumasa Komura, Wataru Fukuokaya, Takahiro Adachi, Yosuke Hirasawa, Takeshi Hashimoto, Atsuhiko Yoshizawa, Masanobu Saruta, Mamoru Hashimoto, Takuya Higashio, Shuya Tsuchida, Kazuki Nishimura, Takuya Tsujino, Ko Nakamura, Tatsuo Fukushima, Kyosuke Nishio, Shutaro Yamamoto, Kosuke Iwatani, Fumihiko Urabe, Keiichiro Mori, Takafumi Yanagisawa, Shunsuke Tsuduki, Kiyoshi Takahara, Teruo Inamoto, Jun Miki, Kazutoshi Fujita, Takahiro Kimura, Yoshio Ohno, Ryoichi Shiroki, Hirotsugu Uemura, Haruhito Azuma","doi":"10.1007/s11523-024-01068-7","DOIUrl":"10.1007/s11523-024-01068-7","url":null,"abstract":"<p><strong>Background: </strong>Enfortumab vedotin (EV), an antibody-drug conjugate that targets Nectin-4, is used for patients with metastatic urothelial carcinoma who have experienced progression on platinum-based chemotherapy and checkpoint inhibitors. Despite the widespread use of the drug, evidence remains scarce regarding clinical indicators that can predict the response to EV treatment.</p><p><strong>Objective: </strong>We aimed to explore the predictive value of clinical indicators derived from peripheral blood tests for treatment responses to EV.</p><p><strong>Methods: </strong>We utilized records of 109 patients with metastatic urothelial carcinoma treated by EV from our multi-institutional dataset. Receiver operating characteristic curve analyses for predicting objective responses including several indicators from blood examinations, such as C-reactive protein-albumin ratio (CAR), hemoglobin, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and lactate dehydrogenase, were performed. The optimal cutoff points were determined by the Youden index. Logistic regression analyses for achieving objective responses to EV treatment were performed among these indicators.</p><p><strong>Results: </strong>The median age of the cohort was 74 years, and the median follow-up duration was 10 months for the entire group. Median overall survival and progression-free survival from the initiation of EV were 12 and 6 months, respectively. The objective response rate and disease control rate were 48% and 70%, respectively. The receiver operating characteristic curve analysis aimed at predicting the achievement of an objective response to EV showed that the concordant index for the CAR was 0.774, significantly surpassing other indicators such as hemoglobin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and serum lactate dehydrogenase. The Youden index identified an optimal cutoff value of 1 for CAR (mg/L for C-reactive protein and g/dL for serum albumin level) in predicting the objective response to EV treatment. Using the cutoff value for the CAR, the cohort was divided into 32 patients (29%) with lower CAR and 77 patients (71%) with higher CAR. The objective response rate was observed to be 84% in the lower CAR group and 32% in the higher CAR group (p < 0.0001). A logistic regression analysis revealed that an Eastern Cooperative Oncology Group Performance Status ≥1 (p = 0.04) and a CAR ≥1 (p < 0.001) were identified as independent predictors for the objective response to EV.</p><p><strong>Conclusions: </strong>The evaluation of the CAR from a concise blood examination at the initiation of EV could effectively predict the treatment response to EV in patients with metastatic urothelial carcinoma after the progression of platinum-based chemotherapy and checkpoint inhibitors.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"635-644"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161468","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":"Correction to: Efficacy and Safety of Neoadjuvant Subcutaneous Envafolimab in dMMR/MSI-H Locally Advanced Colon Cancer.","authors":"Yuan Li, Weili Zhang, Jie Du, Jinlong Hu, Ruixi Hu, Ziyang Zeng, E-Er-Man-Bie-Ke Jin-Si-Han, Shaopu Lian, Hao Wang, Yunfeng Li, Zhizhong Pan, Cheng Feng, Xuan Zhang, Zhenhai Lu","doi":"10.1007/s11523-024-01077-6","DOIUrl":"10.1007/s11523-024-01077-6","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"663"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238248","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":"Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study).","authors":"Ondřej Fiala, Sebastiano Buti, Aristotelis Bamias, Francesco Massari, Renate Pichler, Marco Maruzzo, Enrique Grande, Ugo De Giorgi, Javier Molina-Cerrillo, Emmanuel Seront, Fabio Calabrò, Zin W Myint, Gaetano Facchini, Ray Manneh Kopp, Rossana Berardi, Jakub Kucharz, Maria Giuseppa Vitale, Alvaro Pinto, Luigi Formisano, Thomas Büttner, Carlo Messina, Fernando Sabino M Monteiro, Nicola Battelli, Ravindran Kanesvaran, Tomáš Büchler, Jindřich Kopecký, Daniele Santini, Giulia Claire Giudice, Camillo Porta, Matteo Santoni","doi":"10.1007/s11523-024-01065-w","DOIUrl":"10.1007/s11523-024-01065-w","url":null,"abstract":"<p><strong>Background: </strong>About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care.</p><p><strong>Objective: </strong>This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy.</p><p><strong>Methods: </strong>The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models.</p><p><strong>Results: </strong>Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9-71.3) versus 20.8 (95% CI 12.6-24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31-0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1-40.5) and 13.0 months (95% CI 6.6-23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3-22.4) and 4.9 months (95% CI 3.0-8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively).</p><p><strong>Conclusions: </strong>Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"587-599"},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864075","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}