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Defining the Position of [177Lu]Lu-PSMA Radioligand Therapy in the Treatment Landscape of Metastatic Castration-Resistant Prostate Cancer: A Meta-analysis of Clinical Trials. 确定[177Lu]Lu-PSMA放射配体治疗在转移性去势抵抗性前列腺癌治疗中的地位:临床试验的荟萃分析。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI: 10.1007/s11523-024-01117-1
Chiara Ciccarese, Matteo Bauckneht, Luca Zagaria, Giuseppe Fornarini, Viria Beccia, Francesco Lanfranchi, Germano Perotti, Giada Pinterpe, Fortuna Migliaccio, Giampaolo Tortora, Lucia Leccisotti, Gianmario Sambuceti, Alessandro Giordano, Orazio Caffo, Roberto Iacovelli
{"title":"Defining the Position of [<sup>177</sup>Lu]Lu-PSMA Radioligand Therapy in the Treatment Landscape of Metastatic Castration-Resistant Prostate Cancer: A Meta-analysis of Clinical Trials.","authors":"Chiara Ciccarese, Matteo Bauckneht, Luca Zagaria, Giuseppe Fornarini, Viria Beccia, Francesco Lanfranchi, Germano Perotti, Giada Pinterpe, Fortuna Migliaccio, Giampaolo Tortora, Lucia Leccisotti, Gianmario Sambuceti, Alessandro Giordano, Orazio Caffo, Roberto Iacovelli","doi":"10.1007/s11523-024-01117-1","DOIUrl":"10.1007/s11523-024-01117-1","url":null,"abstract":"<p><strong>Background: </strong>In recent years, theranostics has become a promising approach for treating metastatic castration-resistant prostate cancer (mCRPC), with trials investigating targeted radioligand therapy, particularly using prostate-specific membrane antigen labeled with lutetium-177 ([<sup>177</sup>Lu]Lu-PSMA). The proper position of [<sup>177</sup>Lu]Lu-PSMA in the therapeutic algorithm of mCRPC is yet to be identified.</p><p><strong>Design, setting, and participants: </strong>We conducted a systematic review and meta-analysis of phase II/III randomized controlled trials to assess the efficacy of [<sup>177</sup>Lu]Lu-PSMA in treating mCRPC. Study endpoints included radiographic progression-free survival (rPFS), prostate-specific antigen-PFS, objective response rate, and overall survival.</p><p><strong>Outcome measurements and statistical analysis: </strong>Data were extracted according to the PRISMA statement. Summary hazard ratios (HRs) were calculated using random- or fixed-effects models. Statistical analyses were performed with RevMan software (v.5.2.3).</p><p><strong>Results: </strong>[<sup>177</sup>Lu]Lu-PSMA reduced the risk of rPFS (HR 0.55; 95% confidence interval [CI] 0.43-0.71; p < 0.00001) and prostate-specific antigen-PFS (HR 0.53; 95% CI 0.41-0.67; p < 0.00001), and improved the objective response rate compared with control therapies (response rate 3.55; 95% CI 1.91-6.60; p < 0.0001), whereas no significant cumulative effect on overall survival was documented (HR 0.92; 95% CI 0.65-1.31; p = 0.63). Notably, in a dedicated subanalysis, comparable effects on rPFS were observed when [<sup>177</sup>Lu]Lu-PSMA was compared with active therapy.</p><p><strong>Conclusion: </strong>[<sup>177</sup>Lu]Lu-PSMA has a favorable impact on the radiographic and biochemical control of mCRPC and represents a potential treatment in a scenario where other valuable options are available. Further efforts are required to identify clinical and molecular markers necessary for proper patient stratification.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"103-112"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755427","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}
引用次数: 0
Efficacy and Safety of Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Real-World Studies. 周期蛋白依赖性激酶4/6抑制剂在乳腺癌患者中的疗效和安全性:随机对照试验和真实世界研究的系统回顾和荟萃分析
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-12-10 DOI: 10.1007/s11523-024-01118-0
Hui-Chen Su, Ho-Wei Lin, Ka-Wai Tam
{"title":"Efficacy and Safety of Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Real-World Studies.","authors":"Hui-Chen Su, Ho-Wei Lin, Ka-Wai Tam","doi":"10.1007/s11523-024-01118-0","DOIUrl":"10.1007/s11523-024-01118-0","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of cyclin-dependent kinase (CDK)4/6 inhibitors in patients with breast cancer have been investigated by large-scale trials sponsored by drug companies. A lack of real-world evidence may lead to biases.</p><p><strong>Objective: </strong>We systematically reviewed the large-scale clinical trials and real-world data to investigate the efficacy and safety of CDK4/6 inhibitors in patients with breast cancer.</p><p><strong>Patients and methods: </strong>We searched PubMed, Embase, and Cochrane Library from the inception of each database to January 2024. We included both prospective and retrospective studies reporting the survival outcomes or adverse effects of CDK4/6 inhibitors in patients with breast cancer.</p><p><strong>Results: </strong>We included 41 prospective trials and 80 retrospective studies involving a total of 69,535 patients. Our meta-analysis of double-arm studies revealed that all types of CDK4/6 inhibitors significantly improved overall survival and progression-free survival. The pooled estimates of the 1-year overall survival (OS) rates and 1-year progression-free survival (PFS) rates in single-arm real-world studies were 74.8% and 49.4% for abemaciclib, 84.1% and 55.7% for palbociclib, and 93.4% and 62.2% for ribobiclib, respectively. In terms of adverse effects, Asian patients were significantly more likely to experience neutropenia and increased alanine aminotransferase, whereas Western patients were significantly more likely to have grade 3 or 4 adverse effects and constipation.</p><p><strong>Conclusions: </strong>CDK4/6 inhibitors can improve OS and PFS in patients with advanced breast cancer. The incidence of adverse effects may differ with drugs and with ethnicity. On the basis of our findings, clinicians can select suitable CDK4/6 inhibitors for patients by conducting thorough clinical evaluations.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"71-88"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802118","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}
引用次数: 0
IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma. 癌症中的 IDH1/2 基因突变:统一认识,挖掘软骨肉瘤的治疗潜力。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-11-15 DOI: 10.1007/s11523-024-01115-3
Shriya Deshmukh, Ciara Kelly, Gabriel Tinoco
{"title":"IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma.","authors":"Shriya Deshmukh, Ciara Kelly, Gabriel Tinoco","doi":"10.1007/s11523-024-01115-3","DOIUrl":"10.1007/s11523-024-01115-3","url":null,"abstract":"<p><p>Chondrosarcomas, a rare form of bone sarcomas with multiple subtypes, pose a pressing clinical challenge for patients with advanced or metastatic disease. The lack of US Food and Drug Administration (FDA)-approved medications underscores the urgent need for further research and development in this area. Patients and their families face challenges as there are no systemic therapeutic options available with substantial effectiveness. A significant number (50-80%) of chondrosarcomas have a mutation in the isocitrate dehydrogenase (IDH) genes. This review focuses on IDH-mediated pathogenesis and recent pharmacological advances with novel IDH inhibitors, explores their potential therapeutic value, and proposes potential future avenues for clinical trials combining IDH inhibitors with other systemic agents for chondrosarcomas.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"13-25"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639812","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}
引用次数: 0
Risk and Benefit for Basket Trials in Oncology: A Systematic Review and Meta-Analysis. 肿瘤学篮式试验的风险与收益:系统回顾与元分析》。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-10-26 DOI: 10.1007/s11523-024-01107-3
Katarzyna Klas, Karolina Strzebonska, Lucja Zaborowska, Tomasz Krawczyk, Alicja Włodarczyk, Urszula Bąk-Kuchejda, Maciej Polak, Simon Van Wambeke, Marcin Waligora
{"title":"Risk and Benefit for Basket Trials in Oncology: A Systematic Review and Meta-Analysis.","authors":"Katarzyna Klas, Karolina Strzebonska, Lucja Zaborowska, Tomasz Krawczyk, Alicja Włodarczyk, Urszula Bąk-Kuchejda, Maciej Polak, Simon Van Wambeke, Marcin Waligora","doi":"10.1007/s11523-024-01107-3","DOIUrl":"10.1007/s11523-024-01107-3","url":null,"abstract":"<p><strong>Background: </strong>Oncology research is increasingly adopting new clinical trial models that implement the concept of precision medicine. One of these is the basket clinical trial design. Basket clinical trials allow new treatments to be evaluated across multiple tumor types. Patients recruited to basket clinical trials share certain molecular characteristics of their cancer that are predictive of clinical benefit from the experimental treatment.</p><p><strong>Objective: </strong>Our aim was to describe the risks and benefits of basket clinical trials in oncology.</p><p><strong>Methods: </strong>Our study was prospectively registered in PROSPERO (CRD42023406401). We systematically searched PubMed, Embase, and ClinicalTrials.gov for reports of basket clinical trials in oncology published between 1 January, 2001, and 14 June, 2023. We measured the risk by treatment-related adverse events (grades 3, 4, and 5), and the benefit by objective response rate. We also extracted and analyzed data on progression-free survival and overall survival. When possible, data were meta-analyzed.</p><p><strong>Results: </strong>We included 126 arms of 75 basket clinical trials accounting for 7659 patients. The pooled objective response rate was 18.0% (95% confidence interval [CI] 14.8-21.1). The rate of treatment-related death was 0.7% (95% CI 0.4-1.0), while 30.4% (95% CI 24.2-36.7) of patients experienced grade 3/4 drug-related toxicity. The median progression-free survival was 3.1 months (95% CI 2.6-3.9), and the median overall survival was 8.9 months (95% CI 6.7-10.2).</p><p><strong>Conclusions: </strong>Our results provide an empirical basis for communicating about the risks and benefits of basket clinical trials and for refining new models of clinical trials applied in precision medicine.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"89-101"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508407","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}
引用次数: 0
Post-Metastasis Survival of Patients with High-Risk Localized and Locally Advanced Prostate Cancer Undergoing Primary Treatment in the United States: A Retrospective Study. 美国接受初治的高危局部和局部晚期前列腺癌患者转移后的生存率:回顾性研究。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-11-10 DOI: 10.1007/s11523-024-01113-5
Stephen J Freedland, Luis Fernandes, Francesco De Solda, Nasuh Buyukkaramikli, Suneel D Mundle, Sharon A McCarthy, Daniel Labson, Lingfeng Yang, Feng Pan, Carmen Mir
{"title":"Post-Metastasis Survival of Patients with High-Risk Localized and Locally Advanced Prostate Cancer Undergoing Primary Treatment in the United States: A Retrospective Study.","authors":"Stephen J Freedland, Luis Fernandes, Francesco De Solda, Nasuh Buyukkaramikli, Suneel D Mundle, Sharon A McCarthy, Daniel Labson, Lingfeng Yang, Feng Pan, Carmen Mir","doi":"10.1007/s11523-024-01113-5","DOIUrl":"10.1007/s11523-024-01113-5","url":null,"abstract":"<p><strong>Background: </strong>Patients with high-risk localized and locally advanced prostate cancer (HR-LPC/LAPC) have increased risk of metastasis, leading to reduced survival rates. Segmenting the disease course [time to recurrence, recurrence to metastasis, and post-metastasis survival (PMS)] may identify disease states for which the greatest impacts can be made to ultimately improve survival.</p><p><strong>Objective: </strong>Evaluate real-world PMS of patients with HR-LPC/LAPC who received primary radical prostatectomy (RP) or radiotherapy (RT) with or without androgen deprivation therapy (ADT).</p><p><strong>Patients and methods: </strong>Electronic health records from an oncology database were used to assess PMS. Risk of death was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were used to analyze the impact of treatment and time to metastasis (TTM) on PMS. Standardized mortality ratios (SMRs) were calculated for patients with HR-LPC/LAPC versus the US general male population.</p><p><strong>Results: </strong>Overall, 5008 patients with HR-LPC/LAPC were identified, and 1231 developed metastases after primary treatment (RP, n = 885; RT only, n = 262; RT+ADT, n = 84). Age-adjusted PMS HR between the RP and RT only cohorts was 1.19 (p = 0.077) and between RP and RT+ADT cohorts was 1.32 (p = 0.078). TTM was unrelated to PMS in unadjusted (HR 1.01, p = 0.2) and age-adjusted models (HR 0.99, p = 0.3). Relative to pre-metastasis SMRs, post-metastasis SMRs increased eightfold and fivefold in patients treated with RP and RT±ADT, respectively.</p><p><strong>Conclusions: </strong>PMS was unrelated to TTM in patients with HR-LPC/LAPC, suggesting PMS may be independent of the trajectory to development of metastases. Given PMS may be a fixed length of time, delaying the development of metastasis may improve survival in patients with HR-LPC/LAPC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"139-148"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628722","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}
引用次数: 0
Optimal Duration of Consolidation Durvalumab Following Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer: A Multi-institutional Retrospective Study. III 期非小细胞肺癌化疗后 Durvalumab 巩固治疗的最佳持续时间:一项多机构回顾性研究。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-11-07 DOI: 10.1007/s11523-024-01105-5
Hiroshi Doi, Yukinori Matsuo, Noriko Kishi, Masakazu Ogura, Takamasa Mitsuyoshi, Nami Ueki, Kazuhito Ueki, Kota Fujii, Masato Sakamoto, Tomoko Atsuta, Tomohiro Katagiri, Takashi Sakamoto, Masaru Narabayashi, Shuji Ohtsu, Satsuki Fujishiro, Takahiro Kishi, Takashi Mizowaki
{"title":"Optimal Duration of Consolidation Durvalumab Following Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer: A Multi-institutional Retrospective Study.","authors":"Hiroshi Doi, Yukinori Matsuo, Noriko Kishi, Masakazu Ogura, Takamasa Mitsuyoshi, Nami Ueki, Kazuhito Ueki, Kota Fujii, Masato Sakamoto, Tomoko Atsuta, Tomohiro Katagiri, Takashi Sakamoto, Masaru Narabayashi, Shuji Ohtsu, Satsuki Fujishiro, Takahiro Kishi, Takashi Mizowaki","doi":"10.1007/s11523-024-01105-5","DOIUrl":"10.1007/s11523-024-01105-5","url":null,"abstract":"<p><strong>Background: </strong>Although durvalumab has shown promise in improving survival rates in patients with locally advanced non-small cell lung cancer (NSCLC), the ideal duration of treatment has yet to be established.</p><p><strong>Objective: </strong>The primary objective of this study was to determine the optimal number of durvalumab cycles following definitive chemoradiotherapy for locally advanced NSCLC.</p><p><strong>Patients and methods: </strong>A total of 178 patients who received chemoradiotherapy for stage III NSCLC at 15 institutions were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were assessed according to the number of consolidation durvalumab cycles by landmark analysis. Landmark analyses were performed at 3-month intervals from the start of durvalumab treatment to 9 months.</p><p><strong>Results: </strong>The median number of durvalumab cycles was 16 (range 1-27). PFS and OS were significantly better in patients who received ≥20 cycles of durvalumab than in those who did not (p < 0.001 and p < 0.001, respectively). In landmark analysis, significant differences were observed in PFS from 0 to 6 months and OS from 3 to 6 months between patients who continued durvalumab after the time point and those who did not. However, there were no significant differences in PFS or OS between patients who received 13-19 or ≥20 cycles of durvalumab at 9 months.</p><p><strong>Conclusions: </strong>Durvalumab should be administered for more than 6 months to contribute to the main benefits of consolidation therapy following chemoradiotherapy.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"161-169"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604615","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}
引用次数: 0
Unveiling the Digital Evolution of Molecular Tumor Boards. 揭示分子肿瘤板的数字进化。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1007/s11523-024-01109-1
Sebastian Lutz, Alicia D'Angelo, Sonja Hammerl, Maximilian Schmutz, Rainer Claus, Nina M Fischer, Frank Kramer, Zaynab Hammoud
{"title":"Unveiling the Digital Evolution of Molecular Tumor Boards.","authors":"Sebastian Lutz, Alicia D'Angelo, Sonja Hammerl, Maximilian Schmutz, Rainer Claus, Nina M Fischer, Frank Kramer, Zaynab Hammoud","doi":"10.1007/s11523-024-01109-1","DOIUrl":"10.1007/s11523-024-01109-1","url":null,"abstract":"<p><p>Molecular tumor boards (MTB) are interdisciplinary conferences involving various experts discussing patients with advanced tumors, to derive individualized treatment suggestions based on molecular variants. These discussions involve using heterogeneous internal data, such as patient clinical data, but also external resources such as knowledge databases for annotations and search for relevant clinical studies. This imposes a certain level of complexity that requires huge effort to homogenize the data and use it in a speedy manner to reach the needed treatment. For this purpose, most institutions involving an MTB are heading toward automation and digitalization of the process, hence reducing manual work requiring human intervention and subsequently time in deriving personalized treatment suggestions. The tools are also used to better visualize the patient's data, which allows a refined overview for the board members. In this paper, we present the results of our thorough literature research about MTBs, their process, the most common knowledge bases, and tools used to support this decision-making process.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"27-43"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751444","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}
引用次数: 0
Open-Label, Multicenter, Phase I Study to Assess Safety and Tolerability of Adavosertib Plus Durvalumab in Patients with Advanced Solid Tumors. 评估 Adavosertib 加 Durvalumab 对晚期实体瘤患者安全性和耐受性的开放标签、多中心 I 期研究。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-11-19 DOI: 10.1007/s11523-024-01110-8
Manish R Patel, Gerald S Falchook, Judy S Wang, Esteban Rodrigo Imedio, Sanjeev Kumar, Kowser Miah, Ganesh M Mugundu, Suzanne F Jones, David R Spigel, Erika P Hamilton
{"title":"Open-Label, Multicenter, Phase I Study to Assess Safety and Tolerability of Adavosertib Plus Durvalumab in Patients with Advanced Solid Tumors.","authors":"Manish R Patel, Gerald S Falchook, Judy S Wang, Esteban Rodrigo Imedio, Sanjeev Kumar, Kowser Miah, Ganesh M Mugundu, Suzanne F Jones, David R Spigel, Erika P Hamilton","doi":"10.1007/s11523-024-01110-8","DOIUrl":"10.1007/s11523-024-01110-8","url":null,"abstract":"<p><strong>Background: </strong>Adavosertib (AZD1775) is a small-molecule Wee1 inhibitor. Durvalumab is a PD-L1 inhibitor.</p><p><strong>Objective: </strong>The safety, tolerability, pharmacokinetics, and preliminary antitumor activity of adavosertib plus durvalumab were evaluated in patients with refractory solid tumors to define the maximum tolerated dose (MTD) and recommended phase II dose (RP2D).</p><p><strong>Patients and methods: </strong>This phase 1, non-randomized, open-label study determined MTD/RP2D using dose-escalation cohorts. Eligible patients had histologically confirmed tumors refractory to standard therapy or for which no standard of care existed.</p><p><strong>Results: </strong>A total of 55 patients received adavosertib with durvalumab. Overall, 3/52 evaluable patients experienced dose-limiting toxicities (DLTs; two grade 3 nausea, one grade 3 diarrhea that did not respond to care within 48 h). The most frequent (in > 5% of patients) treatment-emergent grade ≥ 3 toxicities were fatigue, diarrhea, nausea, anemia, and abdominal pain. MTD for twice-daily (bid) adavosertib dosing was oral adavosertib 150 mg bid (3 days on/4 days off; treatment days 15-17 and 22-24 of a 28-day cycle) with intravenous durvalumab 1500 mg four times a week (Q4W), which was also the RP2D. MTD for once-daily (qd) adavosertib dosing was oral adavosertib 300 mg qd (5 days on/2 days off; treatment days 15-19 and 22-26 of a 28-day cycle) with intravenous durvalumab 1500 mg Q4W.</p><p><strong>Conclusions: </strong>This study defined the MTD/RP2D of adavosertib plus durvalumab in patients with advanced solid tumors. The safety profile of adavosertib with durvalumab was consistent with the known safety data of each agent. Findings provide preliminary evidence of limited antitumor activity of adavosertib plus durvalumab.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT02617277 (registration: 30 November 2015).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"127-138"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669283","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}
引用次数: 0
Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis. 肌肉浸润性尿路上皮癌的辅助免疫检查点抑制剂:最新系统综述、Meta 分析和网络 Meta 分析。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-11-13 DOI: 10.1007/s11523-024-01114-4
Takafumi Yanagisawa, Keiichiro Mori, Akihiro Matsukawa, Tatsushi Kawada, Satoshi Katayama, Ekaterina Laukhtina, Pawel Rajwa, Fahad Quhal, Benjamin Pradere, Wataru Fukuokaya, Kosuke Iwatani, Luca Afferi, Gautier Marcq, Laura S Mertens, Andrea Gallioli, Karl H Tully, Jorge Caño-Velasco, José Daniel Subiela, Yasmin Abu-Ghanem, Elisabeth Grobet-Jeandin, Francesco Del Giudice, Renate Pichler, Jeremy Yuen-Chun Teoh, Marco Moschini, Wojciech Krajewski, Jun Miki, Shahrokh F Shariat, Takahiro Kimura
{"title":"Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.","authors":"Takafumi Yanagisawa, Keiichiro Mori, Akihiro Matsukawa, Tatsushi Kawada, Satoshi Katayama, Ekaterina Laukhtina, Pawel Rajwa, Fahad Quhal, Benjamin Pradere, Wataru Fukuokaya, Kosuke Iwatani, Luca Afferi, Gautier Marcq, Laura S Mertens, Andrea Gallioli, Karl H Tully, Jorge Caño-Velasco, José Daniel Subiela, Yasmin Abu-Ghanem, Elisabeth Grobet-Jeandin, Francesco Del Giudice, Renate Pichler, Jeremy Yuen-Chun Teoh, Marco Moschini, Wojciech Krajewski, Jun Miki, Shahrokh F Shariat, Takahiro Kimura","doi":"10.1007/s11523-024-01114-4","DOIUrl":"10.1007/s11523-024-01114-4","url":null,"abstract":"<p><strong>Context: </strong>Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens.</p><p><strong>Objective: </strong>To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials.</p><p><strong>Evidence acquisition: </strong>In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features.</p><p><strong>Evidence synthesis: </strong>Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival.</p><p><strong>Conclusions: </strong>Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"57-69"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628698","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}
引用次数: 0
Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial. 对治疗无效和既往接受过治疗的晚期肾细胞癌患者使用 Fruquintinib 加 Sintilimab 的 Ib/II 期临床试验结果:Ib/II期临床试验结果。
IF 4.4 3区 医学
Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2025-01-13 DOI: 10.1007/s11523-024-01120-6
Hua Xu, Xin Yao, Zhisong He, Hong Luo, Guiling Li, Jianming Guo, Lei Diao, Yu Fan, Yuan Li, Jiquan Fan, Xiaoyi Hu, Puhan Lu, Haiyan Shi, Keyan Chen, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su, Dingwei Ye
{"title":"Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.","authors":"Hua Xu, Xin Yao, Zhisong He, Hong Luo, Guiling Li, Jianming Guo, Lei Diao, Yu Fan, Yuan Li, Jiquan Fan, Xiaoyi Hu, Puhan Lu, Haiyan Shi, Keyan Chen, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su, Dingwei Ye","doi":"10.1007/s11523-024-01120-6","DOIUrl":"10.1007/s11523-024-01120-6","url":null,"abstract":"<p><strong>Background: </strong>Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).</p><p><strong>Objective: </strong>We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).</p><p><strong>Patients and methods: </strong>Eligible patients had pathologically confirmed advanced ccRCC. Patients received fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus sintilimab 200 mg every 3 weeks in 3-week cycles. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1.</p><p><strong>Results: </strong>By March 31, 2023, 42 patients (median age 58.9 years; 81.0% male) had been treated in the RCC cohort. Among treatment-naive patients (n = 22), confirmed ORR was 68.2% (95% confidence interval [CI] 45.1-86.1). The median progression-free survival (PFS) was not reached, and 18-month PFS rate was 59.4%. Among previously treated patients (n = 20), the confirmed ORR was 60.0% (95% CI 36.1-80.9), and the median PFS was 15.9 (95% CI 5.4-19.3) months. All patients had adverse events related to study treatment, 52.4% of which were grade ≥ 3 in severity. Treatment-related adverse events with an incidence of ≥ 40% included proteinuria, hypothyroidism, hypercholesterolemia, hypertriglyceridemia, and hypoalbuminemia.</p><p><strong>Conclusions: </strong>Fruquintinib plus sintilimab demonstrated promising efficacy in advanced ccRCC and was well tolerated. A phase III study (FRUSICA-02) using this combination regimen in patients with previously treated advanced ccRCC is ongoing.</p><p><strong>Trial registration number: </strong>The study was registered with ClinicalTrials.gov (NCT03903705).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"113-125"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979272","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}
引用次数: 0
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