Pub Date : 2024-10-15DOI: 10.1007/s11523-024-01101-9
Robert I Haddad, Kevin Harrington
For the past two decades, cisplatin-based adjuvant chemoradiotherapy (CRT) has remained the standard of care for patients with resected, locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) who are at high risk of disease recurrence. However, many patients are deemed ineligible for cisplatin-based CRT because of poor performance status, advanced age, poor renal function, or hearing loss. Outcomes with radiotherapy alone remain poor, so patients at high risk of disease recurrence who are ineligible to receive cisplatin represent a population with a significant unmet medical need. Although clinical guidelines and consensus documents have provided definitions for cisplatin ineligibility, there are still areas of debate, including thresholds for age and renal impairment as well as criteria for hearing loss. Treatment selection for patients with resected, high-risk LA SCCHN who are deemed ineligible to receive cisplatin is often based on clinical judgment, as treatment options are not clearly specified in international guidelines. Therefore, there is an urgent need to develop alternative systemic treatments to be used in combination with radiotherapy. In this podcast, we share our clinical experience and provide our perspectives related to cisplatin ineligibility in patients with LA SCCHN, discuss the limited clinical evidence for adjuvant treatment of patients with resected, high-risk disease, and highlight ongoing clinical trials that have the potential to provide new treatment options in this setting.
过去二十年来,顺铂辅助化放疗(CRT)一直是治疗切除的局部晚期头颈部鳞状细胞癌(LA SCCHN)高复发风险患者的标准疗法。然而,许多患者由于表现不佳、年事已高、肾功能不佳或听力丧失,被认为不符合接受顺铂为基础的 CRT 治疗的条件。单纯放疗的疗效仍然不佳,因此,不符合接受顺铂治疗条件的高复发风险患者代表着有大量医疗需求未得到满足的人群。尽管临床指南和共识文件已经提供了不符合顺铂治疗条件的定义,但仍存在争议,包括年龄和肾功能损害的阈值以及听力损失的标准。对于被认为不符合顺铂治疗条件的切除性高风险 LA SCCHN 患者,其治疗选择往往基于临床判断,因为国际指南中并未明确规定治疗方案。因此,迫切需要开发与放疗联合使用的替代性全身治疗方法。在本期播客中,我们将分享我们的临床经验,并就LA SCCHN患者不符合顺铂治疗条件的问题提出我们的观点,讨论切除的高风险疾病患者辅助治疗的有限临床证据,并重点介绍正在进行的有可能为这种情况提供新治疗方案的临床试验。
{"title":"Physician Perspectives on the Management of Patients with Resected High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck Who Are Ineligible to Receive Cisplatin: A Podcast.","authors":"Robert I Haddad, Kevin Harrington","doi":"10.1007/s11523-024-01101-9","DOIUrl":"https://doi.org/10.1007/s11523-024-01101-9","url":null,"abstract":"<p><p>For the past two decades, cisplatin-based adjuvant chemoradiotherapy (CRT) has remained the standard of care for patients with resected, locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) who are at high risk of disease recurrence. However, many patients are deemed ineligible for cisplatin-based CRT because of poor performance status, advanced age, poor renal function, or hearing loss. Outcomes with radiotherapy alone remain poor, so patients at high risk of disease recurrence who are ineligible to receive cisplatin represent a population with a significant unmet medical need. Although clinical guidelines and consensus documents have provided definitions for cisplatin ineligibility, there are still areas of debate, including thresholds for age and renal impairment as well as criteria for hearing loss. Treatment selection for patients with resected, high-risk LA SCCHN who are deemed ineligible to receive cisplatin is often based on clinical judgment, as treatment options are not clearly specified in international guidelines. Therefore, there is an urgent need to develop alternative systemic treatments to be used in combination with radiotherapy. In this podcast, we share our clinical experience and provide our perspectives related to cisplatin ineligibility in patients with LA SCCHN, discuss the limited clinical evidence for adjuvant treatment of patients with resected, high-risk disease, and highlight ongoing clinical trials that have the potential to provide new treatment options in this setting.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475321","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}
Background: The clinical outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced lung adenocarcinoma vary according to real-world data.
Objective: In this study, we aimed to investigate the treatment discontinuation (TTD) and overall survival (OS) of patients with ALK+ advanced lung adenocarcinoma treated with first-line ALK-TKIs in Taiwan.
Patients and methods: This retrospective study evaluated all advanced lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2020 who had ALK rearrangement and received ALK-TKI treatment, using data from Taiwan's National Health Insurance Research Database (NHIRD). The TKI treatment sequences were classified into first generation (G1: crizotinib), second generation (G2: ceritinib, alectinib, brigatinib), and third generation (G3: lorlatinib).
Results: A total of 587 patients were analyzed, with a median age of 60.0 years, 91 (15.5%) aged ≥ 74 years, 293 (49.9%) female, 397 (67.6%) never smoked, and 534 (91.0%) with stage IV disease. Patients who received next-generation ALK-TKIs during the treatment course had longer median time to ALK-TKI TTD and OS. The TTD of the G1, G1+2, G1+2+3, G2, and G2+3 groups was 7.5 (5.4-11.1), 40.6 (29.4-not calculated (NC)), 50.3 (41.3-NC), 34.3 (29.2-43.0), and 36.3 (22.4-NC) months, respectively (p < 0.001). The median OS of the patients in the G1, G1+2, G1+2+3, G2, and G2+3 groups was 10.6 (7.5-14.6), not reached (NR) (NC-NC), NR (NC-NC), 43.0 (36.3-NC), and NR (30.3-NC) months, respectively (p < 0.001). Compared with treatment with crizotinib alone, the multivariate analysis revealed that treatment with next-generation TKIs was independently associated with longer TTD (G1+2 (hazard ratio (HR), 0.24; 95% CI 0.17-0.33; p < 0.001), G1+2+3 or G1+3 (HR, 0.17; 95% confidence interval (CI), 0.10-0.28; p < 0.001), G2 (HR, 0.26; 95% CI 0.19-0.36; p < 0.001), and G2+3 (HR, 0.25; 95% CI 0.14-0.44; p < 0.001)) and median OS (G12 (HR, 0.24; 95% CI 0.17-0.35; p < 0.001), G1+2+3 or G1+3 (HR, 0.09; 95% CI 0.04-0.21; p < 0.001), G2 (HR, 0.22; 95% CI 0.15-0.31; p < 0.001), and G2+3 (HR, 0.20; 95% CI 0.10-0.42; p < 0.001)).
Conclusions: For patients with ALK+ NSCLC, treatments including next-generation ALK-TKIs were independently associated with longer survival outcomes.
背景:根据实际数据,无性淋巴瘤激酶阳性(ALK+)晚期肺腺癌患者的临床结局各不相同:在这项研究中,我们旨在调查在台湾接受一线ALK-TKIs治疗的ALK+晚期肺腺癌患者的治疗中断(TTD)和总生存期(OS):这项回顾性研究利用台湾国民健康保险研究数据库(NHIRD)的数据,评估了2017年至2020年期间在国立台湾癌症登记中心登记的所有晚期肺腺癌患者,这些患者均有ALK重排并接受了ALK-TKI治疗。TKI治疗序列分为第一代(G1:克唑替尼)、第二代(G2:色瑞替尼、阿来替尼、布瑞加替尼)和第三代(G3:洛拉替尼):共分析了 587 名患者,中位年龄为 60.0 岁,91 人(15.5%)年龄≥ 74 岁,293 人(49.9%)为女性,397 人(67.6%)从不吸烟,534 人(91.0%)为 IV 期患者。在治疗过程中接受新一代ALK-TKIs的患者的ALK-TKI TTD和OS中位时间更长。G1、G1+2、G1+2+3、G2和G2+3组的TTD分别为7.5(5.4-11.1)、40.6(29.4-未计算(NC))、50.3(41.3-NC)、34.3(29.2-43.0)和36.3(22.4-NC)个月(P<0.001)。G1、G1+2、G1+2+3、G2和G2+3组患者的中位OS分别为10.6(7.5-14.6)个月、未达到(NR)(NC-NC)个月、NR(NC-NC)个月、43.0(36.3-NC)个月和NR(30.3-NC)个月(P < 0.001)。与单独使用克唑替尼治疗相比,多变量分析显示,使用新一代 TKIs 治疗与更长的 TTD(G1+2(危险比(HR),0.24;95% CI 0.17-0.33;p <0.001)、G1+2+3 或 G1+3(HR,0.17;95% 置信区间(CI),0.10-0.28;p <0.001)、G2(HR,0.26;95% CI 0.19-0.36;P < 0.001)和 G2+3 (HR,0.25;95% CI 0.14-0.44;P < 0.001))和中位 OS(G12(HR,0.24;95% CI 0.17-0.35;P < 0.001)、G1+2+3 或 G1+3 (HR,0.09;95% CI 0.04-0.21;P<0.001)、G2(HR,0.22;95% CI 0.15-0.31;P<0.001)和G2+3(HR,0.20;95% CI 0.10-0.42;P<0.001)).结论:结论:对于ALK+ NSCLC患者,包括新一代ALK-TKIs在内的治疗方法与更长的生存期结局密切相关。
{"title":"Taiwan Nationwide Study of First-Line ALK-TKI Therapy in ALK-Positive Lung Adenocarcinoma.","authors":"Zhe-Rong Zheng, Jia-Jun Wu, Chun-Ju Chiang, Tzu-I Chen, Kun-Chieh Chen, Cheng-Hsiang Chu, Sheng-Yi Lin, Sung-Liang Yu, Wen-Chung Lee, Tsang-Wu Liu, Gee-Chen Chang","doi":"10.1007/s11523-024-01104-6","DOIUrl":"https://doi.org/10.1007/s11523-024-01104-6","url":null,"abstract":"<p><strong>Background: </strong>The clinical outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced lung adenocarcinoma vary according to real-world data.</p><p><strong>Objective: </strong>In this study, we aimed to investigate the treatment discontinuation (TTD) and overall survival (OS) of patients with ALK+ advanced lung adenocarcinoma treated with first-line ALK-TKIs in Taiwan.</p><p><strong>Patients and methods: </strong>This retrospective study evaluated all advanced lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2020 who had ALK rearrangement and received ALK-TKI treatment, using data from Taiwan's National Health Insurance Research Database (NHIRD). The TKI treatment sequences were classified into first generation (G1: crizotinib), second generation (G2: ceritinib, alectinib, brigatinib), and third generation (G3: lorlatinib).</p><p><strong>Results: </strong>A total of 587 patients were analyzed, with a median age of 60.0 years, 91 (15.5%) aged ≥ 74 years, 293 (49.9%) female, 397 (67.6%) never smoked, and 534 (91.0%) with stage IV disease. Patients who received next-generation ALK-TKIs during the treatment course had longer median time to ALK-TKI TTD and OS. The TTD of the G1, G1+2, G1+2+3, G2, and G2+3 groups was 7.5 (5.4-11.1), 40.6 (29.4-not calculated (NC)), 50.3 (41.3-NC), 34.3 (29.2-43.0), and 36.3 (22.4-NC) months, respectively (p < 0.001). The median OS of the patients in the G1, G1+2, G1+2+3, G2, and G2+3 groups was 10.6 (7.5-14.6), not reached (NR) (NC-NC), NR (NC-NC), 43.0 (36.3-NC), and NR (30.3-NC) months, respectively (p < 0.001). Compared with treatment with crizotinib alone, the multivariate analysis revealed that treatment with next-generation TKIs was independently associated with longer TTD (G1+2 (hazard ratio (HR), 0.24; 95% CI 0.17-0.33; p < 0.001), G1+2+3 or G1+3 (HR, 0.17; 95% confidence interval (CI), 0.10-0.28; p < 0.001), G2 (HR, 0.26; 95% CI 0.19-0.36; p < 0.001), and G2+3 (HR, 0.25; 95% CI 0.14-0.44; p < 0.001)) and median OS (G12 (HR, 0.24; 95% CI 0.17-0.35; p < 0.001), G1+2+3 or G1+3 (HR, 0.09; 95% CI 0.04-0.21; p < 0.001), G2 (HR, 0.22; 95% CI 0.15-0.31; p < 0.001), and G2+3 (HR, 0.20; 95% CI 0.10-0.42; p < 0.001)).</p><p><strong>Conclusions: </strong>For patients with ALK+ NSCLC, treatments including next-generation ALK-TKIs were independently associated with longer survival outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401405","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}
Background: Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (AEs), which pose challenges to the continuation of treatment. Although ICIs are widely used in patients with cancer, studies reporting immune-mediated pancreatitis remain scarce.
Objectives: We performed a systematic review and meta-analysis to address current knowledge gaps and provide clinical guidance for ICI-associated pancreatitis and lipase elevation.
Patients and methods: We searched PubMed/Medline, Embase, and Web of Science for phase 3 randomized controlled trials (RCTs) evaluating ICIs. The incidence of any-grade and grade 3-5 pancreatitis/lipase elevation was calculated. Then, we performed a random-effect model meta-analysis to pool the odds ratios (ORs) of these outcomes using RCTs evaluating the addition of an ICI to systemic therapy to assess the effect of ICIs on pancreatic AEs. A systematic review of the treatment of ICI-related pancreatitis was also conducted.
Results: The incidence analysis included 81 articles (79 RCTs) comprising 36,871 patients. The incidence of treatment-related pancreatitis was 0.68% (any-grade) and 0.32% (grade 3-5). Meta-analysis revealed that the addition of ICI therapy significantly increased any-grade (OR 2.12, 95% confidence interval [CI] 1.45-3.11, p < 0.001) and grade 3-5 pancreatitis (OR 1.76, 95% CI 1.01-3.08, p < 0.05) with low heterogeneity among ICI subtype subgroups (any-grade: I2 = 0%, p = 0.99; grade 3-5: I2 = 0%, p = 0.63). In analysis of treatment outcome among 146 patients from 53 articles, glucocorticoids were used in 80.6% (n = 108/134) and ICIs were discontinued in 76.5% (n = 101/132; permanent discontinuation: 62.5% [n = 35/56]).
Conclusions: The overall rate of pancreatitis appears low, but the addition of ICI therapy significantly increased the incidence of pancreatitis. These findings provide insight into the incidence and treatment of pancreatitis associated with ICIs.
{"title":"Pancreatitis in Patients with Cancer Receiving Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.","authors":"Mako Koseki, Yoshito Nishimura, Evelyn Elias, Jonathan Estaris, Fnu Chesta, Kensuke Takaoka, Theresa Shao, Nobuyuki Horita, Yu Fujiwara","doi":"10.1007/s11523-024-01098-1","DOIUrl":"https://doi.org/10.1007/s11523-024-01098-1","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (AEs), which pose challenges to the continuation of treatment. Although ICIs are widely used in patients with cancer, studies reporting immune-mediated pancreatitis remain scarce.</p><p><strong>Objectives: </strong>We performed a systematic review and meta-analysis to address current knowledge gaps and provide clinical guidance for ICI-associated pancreatitis and lipase elevation.</p><p><strong>Patients and methods: </strong>We searched PubMed/Medline, Embase, and Web of Science for phase 3 randomized controlled trials (RCTs) evaluating ICIs. The incidence of any-grade and grade 3-5 pancreatitis/lipase elevation was calculated. Then, we performed a random-effect model meta-analysis to pool the odds ratios (ORs) of these outcomes using RCTs evaluating the addition of an ICI to systemic therapy to assess the effect of ICIs on pancreatic AEs. A systematic review of the treatment of ICI-related pancreatitis was also conducted.</p><p><strong>Results: </strong>The incidence analysis included 81 articles (79 RCTs) comprising 36,871 patients. The incidence of treatment-related pancreatitis was 0.68% (any-grade) and 0.32% (grade 3-5). Meta-analysis revealed that the addition of ICI therapy significantly increased any-grade (OR 2.12, 95% confidence interval [CI] 1.45-3.11, p < 0.001) and grade 3-5 pancreatitis (OR 1.76, 95% CI 1.01-3.08, p < 0.05) with low heterogeneity among ICI subtype subgroups (any-grade: I<sup>2</sup> = 0%, p = 0.99; grade 3-5: I<sup>2</sup> = 0%, p = 0.63). In analysis of treatment outcome among 146 patients from 53 articles, glucocorticoids were used in 80.6% (n = 108/134) and ICIs were discontinued in 76.5% (n = 101/132; permanent discontinuation: 62.5% [n = 35/56]).</p><p><strong>Conclusions: </strong>The overall rate of pancreatitis appears low, but the addition of ICI therapy significantly increased the incidence of pancreatitis. These findings provide insight into the incidence and treatment of pancreatitis associated with ICIs.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401404","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}
Pub Date : 2024-10-05DOI: 10.1007/s11523-024-01100-w
Michael F Basin, Carla M Miguel, Joseph M Jacob, Hanan Goldberg, Petros Grivas, Philippe E Spiess, Andrea Necchi, Ashish M Kamat, Dean C Pavlick, Richard S P Huang, Douglas I Lin, Natalie Danziger, Ethan S Sokol, Smruthy Sivakumar, Ryon Graf, Liang Cheng, Neil Vasan, Jeffrey Ross, Alina Basnet, Gennady Bratslavsky
Background: Tumors harboring two or more PIK3CA short variant (SV) ("multi-hit") mutations have been linked to improved outcomes with anti-PIK3CA-targeted therapies in breast cancer. The landscape and clinical implications of multi-hit PIK3CA alterations in clinically advanced prostate cancer (CAPC) remains elusive.
Objective: To evaluate the genomic landscape of single-hit and multi-hit PIK3CA genomic alterations in CAPC.
Patients and methods: The Foundation Medicine FoundationCore database was used to identify 19,978 CAPC tumors that underwent hybrid capture-based comprehensive genomic profiling to evaluate all classes of genomic alterations (GA) and determine tumor mutational burden (TMB), microsatellite instability (MSI), genomic ancestry, single-base substitution mutational signatures, and homologous recombination deficiency signature (HRDsig). Tumor cell PD-L1 expression was determined by IHC (Dako 22C3).
Results: 18,741 (93.8%) tumors were PIK3CA wild type (WT), 1155 (5.8%) featured single PIK3CA SV, and 82 (0.4%) featured multi-hit PIK3CA SVs. Single-hit (6.6 versus 3.8; p < 0.0001) and multi-hit (12.8 versus 3.8; p < 0.0001) featured more driver GA per tumor than PIK3CA WT CAPC, as well as higher prevalence of MMR mutational signature, MSI high status, and TMB levels versus PIK3CA WT (p < 0.0001). Other differences in GA included higher frequencies of GA in BRCA2 in multi-hit versus WT (18.3% versus 8.5%; p = 0.0191), ATM in multi-hit versus WT (13.4% versus 5.6%; p = 0.02) and PTEN in single-hit versus WT (40.2% versus 30.1%; p < 0.0001). Homologous recombination deficiency signatures were higher in PIK3CA WT versus single-hit (11.2% versus 7.6%; p = 0.0002). There were no significant differences in PD-L1 expression among the three groups.
Conclusions: Identification of multi-hit PIK3CA GA in CAPC highlights a potentially unique phenotype that may be associated with response to anti-PIK3CA targeted therapy and checkpoint inhibition, supporting relevant clinical trial designs.
{"title":"Single-Hit and Multi-hit PIK3CA Short Variant Genomic Alterations in Clinically Advanced Prostate Cancer: A Genomic Landscape Study.","authors":"Michael F Basin, Carla M Miguel, Joseph M Jacob, Hanan Goldberg, Petros Grivas, Philippe E Spiess, Andrea Necchi, Ashish M Kamat, Dean C Pavlick, Richard S P Huang, Douglas I Lin, Natalie Danziger, Ethan S Sokol, Smruthy Sivakumar, Ryon Graf, Liang Cheng, Neil Vasan, Jeffrey Ross, Alina Basnet, Gennady Bratslavsky","doi":"10.1007/s11523-024-01100-w","DOIUrl":"https://doi.org/10.1007/s11523-024-01100-w","url":null,"abstract":"<p><strong>Background: </strong>Tumors harboring two or more PIK3CA short variant (SV) (\"multi-hit\") mutations have been linked to improved outcomes with anti-PIK3CA-targeted therapies in breast cancer. The landscape and clinical implications of multi-hit PIK3CA alterations in clinically advanced prostate cancer (CAPC) remains elusive.</p><p><strong>Objective: </strong>To evaluate the genomic landscape of single-hit and multi-hit PIK3CA genomic alterations in CAPC.</p><p><strong>Patients and methods: </strong>The Foundation Medicine FoundationCore database was used to identify 19,978 CAPC tumors that underwent hybrid capture-based comprehensive genomic profiling to evaluate all classes of genomic alterations (GA) and determine tumor mutational burden (TMB), microsatellite instability (MSI), genomic ancestry, single-base substitution mutational signatures, and homologous recombination deficiency signature (HRDsig). Tumor cell PD-L1 expression was determined by IHC (Dako 22C3).</p><p><strong>Results: </strong>18,741 (93.8%) tumors were PIK3CA wild type (WT), 1155 (5.8%) featured single PIK3CA SV, and 82 (0.4%) featured multi-hit PIK3CA SVs. Single-hit (6.6 versus 3.8; p < 0.0001) and multi-hit (12.8 versus 3.8; p < 0.0001) featured more driver GA per tumor than PIK3CA WT CAPC, as well as higher prevalence of MMR mutational signature, MSI high status, and TMB levels versus PIK3CA WT (p < 0.0001). Other differences in GA included higher frequencies of GA in BRCA2 in multi-hit versus WT (18.3% versus 8.5%; p = 0.0191), ATM in multi-hit versus WT (13.4% versus 5.6%; p = 0.02) and PTEN in single-hit versus WT (40.2% versus 30.1%; p < 0.0001). Homologous recombination deficiency signatures were higher in PIK3CA WT versus single-hit (11.2% versus 7.6%; p = 0.0002). There were no significant differences in PD-L1 expression among the three groups.</p><p><strong>Conclusions: </strong>Identification of multi-hit PIK3CA GA in CAPC highlights a potentially unique phenotype that may be associated with response to anti-PIK3CA targeted therapy and checkpoint inhibition, supporting relevant clinical trial designs.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378331","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}
Pub Date : 2024-10-03DOI: 10.1007/s11523-024-01103-7
Sejin Kim, Suat Ying Lee, Jaekyung Cheon, Hyung-Don Kim, Young Gyu Park, Joycelyn Jie Xin Lee, Min-Hee Ryu, Baek-Yeol Ryoo, David Tai, Changhoon Yoo
Background: Atezolizumab-bevacizumab is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). Given the diversity in HCC etiology and its potential impact on the tumor microenvironment, understanding how different liver disease etiologies affect treatment efficacy is important.
Objective: We assessed the influence of liver disease etiology on the efficacy of atezolizumab-bevacizumab and evaluated changes in liver function during treatment with atezolizumab-bevacizumab.
Patients and methods: This study included 390 patients with uHCC treated with first-line atezolizumab-bevacizumab from Asan Medical Center, South Korea, and National Cancer Centre Singapore, Singapore from July 2016 to March 2023. Patients were classified to viral, metabolic dysfunction-associated liver disease (MASLD) and nonviral/non-MASLD groups. Albumin-bilirubin (ALBI) scores were recorded at baseline and every two cycles up to cycle six and at the time of disease progression.
Results: The majority of patients presented with viral etiologies (74.1%), and 17.2% had MASLD. Across etiological groups (viral versus MASLD versus nonviral/non-MASLD) no significant differences in objective response rate (23.2% versus 29.9% versus 23.5%, respectively; p = 0.515), progression-free survival (median 5.4 versus 7.7 versus 6.0 months; p = 0.320), and overall survival (18.1 versus 18.9 versus 14.4 months; p = 0.400) were observed. Among the patients with disease progression, ALBI scores at the time of progression were significantly higher than at baseline. Subsequent therapy was administered significantly less often to patients with ALBI grade 3 at disease progression compared with those with ALBI grades 1 or 2 (48.4% versus 78.8%, p = 0.002) CONCLUSIONS: Atezolizumab-bevacizumab demonstrates consistent efficacy regardless of HCC etiology, supporting its use as a first-line treatment across diverse patient populations. Liver function assessments remain crucial for managing therapy and predicting outcomes.
{"title":"Impact of Etiology on Efficacy Outcomes with Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Retrospective Analysis in Asia-Pacific.","authors":"Sejin Kim, Suat Ying Lee, Jaekyung Cheon, Hyung-Don Kim, Young Gyu Park, Joycelyn Jie Xin Lee, Min-Hee Ryu, Baek-Yeol Ryoo, David Tai, Changhoon Yoo","doi":"10.1007/s11523-024-01103-7","DOIUrl":"https://doi.org/10.1007/s11523-024-01103-7","url":null,"abstract":"<p><strong>Background: </strong>Atezolizumab-bevacizumab is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). Given the diversity in HCC etiology and its potential impact on the tumor microenvironment, understanding how different liver disease etiologies affect treatment efficacy is important.</p><p><strong>Objective: </strong>We assessed the influence of liver disease etiology on the efficacy of atezolizumab-bevacizumab and evaluated changes in liver function during treatment with atezolizumab-bevacizumab.</p><p><strong>Patients and methods: </strong>This study included 390 patients with uHCC treated with first-line atezolizumab-bevacizumab from Asan Medical Center, South Korea, and National Cancer Centre Singapore, Singapore from July 2016 to March 2023. Patients were classified to viral, metabolic dysfunction-associated liver disease (MASLD) and nonviral/non-MASLD groups. Albumin-bilirubin (ALBI) scores were recorded at baseline and every two cycles up to cycle six and at the time of disease progression.</p><p><strong>Results: </strong>The majority of patients presented with viral etiologies (74.1%), and 17.2% had MASLD. Across etiological groups (viral versus MASLD versus nonviral/non-MASLD) no significant differences in objective response rate (23.2% versus 29.9% versus 23.5%, respectively; p = 0.515), progression-free survival (median 5.4 versus 7.7 versus 6.0 months; p = 0.320), and overall survival (18.1 versus 18.9 versus 14.4 months; p = 0.400) were observed. Among the patients with disease progression, ALBI scores at the time of progression were significantly higher than at baseline. Subsequent therapy was administered significantly less often to patients with ALBI grade 3 at disease progression compared with those with ALBI grades 1 or 2 (48.4% versus 78.8%, p = 0.002) CONCLUSIONS: Atezolizumab-bevacizumab demonstrates consistent efficacy regardless of HCC etiology, supporting its use as a first-line treatment across diverse patient populations. Liver function assessments remain crucial for managing therapy and predicting outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366624","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}
Pub Date : 2024-10-01DOI: 10.1007/s11523-024-01099-0
Ondřej Fiala, Francesco Massari, Umberto Basso, Patrizia Giannatempo, Enrique Grande, Sebastiano Buti, Zin W Myint, Ugo De Giorgi, Renate Pichler, Francesco Grillone, Yüksel Ürün, Fabio Calabrò, Maria T Bourlon, Luca Galli, Ravindran Kanesvaran, Giandomenico Roviello, Jakub Kucharz, Mimma Rizzo, Se Hoon Park, Linda Cerbone, Emmanuel Seront, Carlo Messina, Javier Molina-Cerrillo, Daniele Santini, Akihiro Yano, Lorena Incorvaia, Martina Catalano, Alvaro Pinto, Luigi Formisano, Andrey Soares, Gaetano Facchini, Giuseppe Fornarini, Alexandr Poprach, Sara Elena Rebuzzi, Cecilia Nasso, Gian Paolo Spinelli, Martin Angel, Marco Stellato, Deniz Tural, Gaetano Aurilio, Ilana Epstein, Francesco Carrozza, Fernando Sabino Marques Monteiro, Giovanni Benedetti, Tomáš Büchler, Cinzia Ortega, Roubini Zakopoulou, Nicola Battelli, Camillo Porta, Joaquin Bellmunt, Shilpa Gupta, Matteo Santoni
Background: Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy.
Objective: The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2EV study.
Patients and methods: The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models.
Results: Median OS and PFS were 12.7 (95% CI 10.2-14.1) and 7.9 (95% CI 6.4-9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1-11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia.
Conclusions: The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab.
背景:恩福单抗韦多汀(EV)已被批准用于治疗既往接受过铂类化疗后又接受过免疫检查点抑制剂治疗的局部晚期/转移性尿路上皮癌(la/mUC)患者。然而,关键临床试验并不包括曾接受过阿维列单抗维持治疗的患者:本回顾性分析旨在评估ARON-2EV研究入组的mUC患者接受阿维列单抗治疗后EV的有效性:研究纳入了182例在阿维鲁单抗维持治疗后接受EV治疗的mUC患者。主要目的是评估临床结果,包括无进展生存期(PFS)、总生存期(OS)、总反应率(ORR)和反应持续时间(DoR)。统计分析包括费舍尔精确检验、卡普兰-梅耶法、对数秩检验和单变量/多变量考克斯比例危险回归模型:中位OS和PFS分别为12.7个月(95% CI 10.2-14.1)和7.9个月(95% CI 6.4-9.9)。5%的患者获得完全应答(CR),34%的患者获得部分应答(PR),ORR为39%。获得 CR/PR 的患者的 DoR 为 10.9 个月(95% CI 8.1-11.4)。≥3级周围神经病变和皮疹的发生率为9%,其次是8%的≥3级腹泻和4%的≥3级高血糖:我们的大型国际回顾性研究结果证实了EV的有效性,并赞同在前线铂类化疗后接受EV治疗并随后接受阿维列单抗维持治疗的mUC患者中使用EV。
{"title":"Enfortumab Vedotin Following Platinum Chemotherapy and Avelumab Maintenance in Patients with Metastatic Urothelial Carcinoma: A Retrospective Data from the ARON-2<sup>EV</sup> Study.","authors":"Ondřej Fiala, Francesco Massari, Umberto Basso, Patrizia Giannatempo, Enrique Grande, Sebastiano Buti, Zin W Myint, Ugo De Giorgi, Renate Pichler, Francesco Grillone, Yüksel Ürün, Fabio Calabrò, Maria T Bourlon, Luca Galli, Ravindran Kanesvaran, Giandomenico Roviello, Jakub Kucharz, Mimma Rizzo, Se Hoon Park, Linda Cerbone, Emmanuel Seront, Carlo Messina, Javier Molina-Cerrillo, Daniele Santini, Akihiro Yano, Lorena Incorvaia, Martina Catalano, Alvaro Pinto, Luigi Formisano, Andrey Soares, Gaetano Facchini, Giuseppe Fornarini, Alexandr Poprach, Sara Elena Rebuzzi, Cecilia Nasso, Gian Paolo Spinelli, Martin Angel, Marco Stellato, Deniz Tural, Gaetano Aurilio, Ilana Epstein, Francesco Carrozza, Fernando Sabino Marques Monteiro, Giovanni Benedetti, Tomáš Büchler, Cinzia Ortega, Roubini Zakopoulou, Nicola Battelli, Camillo Porta, Joaquin Bellmunt, Shilpa Gupta, Matteo Santoni","doi":"10.1007/s11523-024-01099-0","DOIUrl":"https://doi.org/10.1007/s11523-024-01099-0","url":null,"abstract":"<p><strong>Background: </strong>Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy.</p><p><strong>Objective: </strong>The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2<sup>EV</sup> study.</p><p><strong>Patients and methods: </strong>The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models.</p><p><strong>Results: </strong>Median OS and PFS were 12.7 (95% CI 10.2-14.1) and 7.9 (95% CI 6.4-9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1-11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia.</p><p><strong>Conclusions: </strong>The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362122","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}
Background: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce.
Objective: We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey.
Patients and methods: This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024.
Results: The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33-60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n = 8), followed by NTRK3 (n = 7). The median duration of entrectinib usage was 6.9 (IQR 3.1-16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2-62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0-30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0-48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0-13.5) months.
Conclusions: In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.
{"title":"Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial.","authors":"Feride Yılmaz, Serkan Yaşar, Nil Molinas Mandel, Turgut Kaçan, Melek Özdemir, Gamze Gököz Doğu, Nilay Şengül, Nezih Meydan, Fatma Buğdaycı Başal, Pınar Kubilay Tolunay, Melda Berber Hamamcı, Oğuz Salih Dinçer, Aykut Bahçeci, Leyla Özer, Miraç Ajredini, Önder Kırca, Özlem Yersal, Orçun Can, Meral Günaldı, Gökhan Demir, Şuayib Yalçın","doi":"10.1007/s11523-024-01095-4","DOIUrl":"https://doi.org/10.1007/s11523-024-01095-4","url":null,"abstract":"<p><strong>Background: </strong>Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce.</p><p><strong>Objective: </strong>We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey.</p><p><strong>Patients and methods: </strong>This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024.</p><p><strong>Results: </strong>The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33-60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n = 8), followed by NTRK3 (n = 7). The median duration of entrectinib usage was 6.9 (IQR 3.1-16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2-62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0-30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0-48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0-13.5) months.</p><p><strong>Conclusions: </strong>In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354332","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}
Background: Osimertinib shows higher effectiveness than first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the initial treatment of EGFR-mutated non-small cell lung cancer. However, its superiority in terms of overall survival in the Asian population, especially Japanese patients, remains uncertain.
Objective: To evaluate the survival benefit of osimertinib over other EGFR-TKIs in Japanese patients, using real-world data. METHODS : As part of the Tokushukai REAl-world Data project, a retrospective multi-institutional study across 46 hospitals in Japan was conducted to evaluate the overall survival of patients with advanced EGFR-mutated non-small cell lung cancer using propensity score matching. The study involved patients receiving osimertinib as the first-line treatment (1L-Osi), those initially treated with other EGFR-TKIs (1L-non-Osi), and those receiving osimertinib after initial EGFR-TKI treatment (2L/later-Osi) between April 2010 and December 2022 and followed up until April 2023.
Results: Among 1062 Japanese patients with EGFR-mutated non-small cell lung cancer, 416 (39.2%) received 1L-Osi, while 646 (60.8%) received 1L-non-Osi, including 139 (13.1%) who received 2L/later-Osi. Within these groups, 416 (39.2%), 293 (27.6%), and 75 (7.1%) patients received first-line EGFR-TKI treatment post-osimertinib approval as a later-line treatment in Japan (March 2016). After propensity score matching, the overall survival of the 1L-Osi group was comparable to that of the 1L-non-Osi group in the post-March 2016 subset (n = 283, 42.0 vs 42.4 months). Similar trends were observed in the Del19 and L858R subgroups. The median overall survival of the 2L/later-Osi group was notably long: 60.2 months post-March 2016 (n = 75). A subgroup analysis based on initial EGFR-TKI treatment in the 1L-non-Osi and 2L/later-Osi groups revealed no significant differences among the gefitinib, erlotinib, and afatinib groups.
Conclusions: Based on real-world data, osimertinib did not show a significant improvement in overall survival compared to other EGFR-TKIs as a first-line treatment for EGFR-mutated advanced non-small cell lung cancer in the Japanese (Asian) population.
Clinical trial registration: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry on 9 March, 2023 (identification UMIN000050552).
{"title":"Impact of First-Line Osimertinib and Other EGFR-Tyrosine Kinase Inhibitors on Overall Survival in Untreated Advanced EGFR-Mutated Non-small Cell Lung Cancer in Japan: Updated Data from TREAD Project 01.","authors":"Makoto Hibino, Yoshinori Imamura, Rai Shimoyama, Tomoya Fukui, Ryuta Fukai, Akihiko Iwase, Yukihiro Tamura, Yusuke Chihara, Takafumi Okabe, Kiyoaki Uryu, Tadahisa Okuda, Masataka Taguri, Hironobu Minami","doi":"10.1007/s11523-024-01094-5","DOIUrl":"https://doi.org/10.1007/s11523-024-01094-5","url":null,"abstract":"<p><strong>Background: </strong>Osimertinib shows higher effectiveness than first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the initial treatment of EGFR-mutated non-small cell lung cancer. However, its superiority in terms of overall survival in the Asian population, especially Japanese patients, remains uncertain.</p><p><strong>Objective: </strong>To evaluate the survival benefit of osimertinib over other EGFR-TKIs in Japanese patients, using real-world data. METHODS : As part of the Tokushukai REAl-world Data project, a retrospective multi-institutional study across 46 hospitals in Japan was conducted to evaluate the overall survival of patients with advanced EGFR-mutated non-small cell lung cancer using propensity score matching. The study involved patients receiving osimertinib as the first-line treatment (1L-Osi), those initially treated with other EGFR-TKIs (1L-non-Osi), and those receiving osimertinib after initial EGFR-TKI treatment (2L/later-Osi) between April 2010 and December 2022 and followed up until April 2023.</p><p><strong>Results: </strong>Among 1062 Japanese patients with EGFR-mutated non-small cell lung cancer, 416 (39.2%) received 1L-Osi, while 646 (60.8%) received 1L-non-Osi, including 139 (13.1%) who received 2L/later-Osi. Within these groups, 416 (39.2%), 293 (27.6%), and 75 (7.1%) patients received first-line EGFR-TKI treatment post-osimertinib approval as a later-line treatment in Japan (March 2016). After propensity score matching, the overall survival of the 1L-Osi group was comparable to that of the 1L-non-Osi group in the post-March 2016 subset (n = 283, 42.0 vs 42.4 months). Similar trends were observed in the Del19 and L858R subgroups. The median overall survival of the 2L/later-Osi group was notably long: 60.2 months post-March 2016 (n = 75). A subgroup analysis based on initial EGFR-TKI treatment in the 1L-non-Osi and 2L/later-Osi groups revealed no significant differences among the gefitinib, erlotinib, and afatinib groups.</p><p><strong>Conclusions: </strong>Based on real-world data, osimertinib did not show a significant improvement in overall survival compared to other EGFR-TKIs as a first-line treatment for EGFR-mutated advanced non-small cell lung cancer in the Japanese (Asian) population.</p><p><strong>Clinical trial registration: </strong>This study was registered at the University Hospital Medical Information Network Clinical Trials Registry on 9 March, 2023 (identification UMIN000050552).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296035","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}
Pub Date : 2024-09-20DOI: 10.1007/s11523-024-01086-5
Jeremy David Kratz, Alyssa Barchet Klein, Courtney Beth Gray, Angela Märten, Hanna-Liisa Vilu, Jennifer Francesca Knight, Alexandra Kumichel, Makoto Ueno
Biliary tract cancer (BTC) is a rare and aggressive malignancy that is anatomically classified as gallbladder cancer (GBC), extra- and intra-hepatic cholangiocarcinoma (eCCA and iCCA) and ampullary cancer (AC). BTC is often diagnosed at an advanced stage when treatment options are limited and patients have a poor prognosis, so the identification of new drug targets is of critical importance. BTC is molecularly diverse and harbours different therapeutically actionable biomarkers, including mouse double minute 2 homolog (MDM2), which is currently being investigated as a drug target. The aim of this targeted review was to evaluate and synthesise evidence on the epidemiology of BTC and its subtypes in different geographic regions and on the frequency of MDM2 amplifications in BTC tumours. Epidemiological studies (N = 33) consistently demonstrated high incidence rates in South and Central Asia for BTC overall (up to 9.00/100,000) and for all subtypes, with much lower rates in Europe and the US. Among the different types of BTC, the highest global incidence was observed for CCA, mainly driven by iCCA (1.4/100,000), followed by GBC (1.2/100,000) and AC (0.18-0.93 per 100,000). Studies of MDM2 in BTC (N = 19) demonstrated variable frequency of MDM2 amplification according to subtype, with consistently high MDM2 amplification rates in GBC (up to 17.5%), and lower rates in CCA (up to 4.4%). The results from this literature review highlight the geographic heterogeneity of BTC and the need for standardised clinicopathologic assessment and reporting to allow cross-study comparisons.
{"title":"The Epidemiology of Biliary Tract Cancer and Associated Prevalence of MDM2 Amplification: A Targeted Literature Review.","authors":"Jeremy David Kratz, Alyssa Barchet Klein, Courtney Beth Gray, Angela Märten, Hanna-Liisa Vilu, Jennifer Francesca Knight, Alexandra Kumichel, Makoto Ueno","doi":"10.1007/s11523-024-01086-5","DOIUrl":"https://doi.org/10.1007/s11523-024-01086-5","url":null,"abstract":"<p><p>Biliary tract cancer (BTC) is a rare and aggressive malignancy that is anatomically classified as gallbladder cancer (GBC), extra- and intra-hepatic cholangiocarcinoma (eCCA and iCCA) and ampullary cancer (AC). BTC is often diagnosed at an advanced stage when treatment options are limited and patients have a poor prognosis, so the identification of new drug targets is of critical importance. BTC is molecularly diverse and harbours different therapeutically actionable biomarkers, including mouse double minute 2 homolog (MDM2), which is currently being investigated as a drug target. The aim of this targeted review was to evaluate and synthesise evidence on the epidemiology of BTC and its subtypes in different geographic regions and on the frequency of MDM2 amplifications in BTC tumours. Epidemiological studies (N = 33) consistently demonstrated high incidence rates in South and Central Asia for BTC overall (up to 9.00/100,000) and for all subtypes, with much lower rates in Europe and the US. Among the different types of BTC, the highest global incidence was observed for CCA, mainly driven by iCCA (1.4/100,000), followed by GBC (1.2/100,000) and AC (0.18-0.93 per 100,000). Studies of MDM2 in BTC (N = 19) demonstrated variable frequency of MDM2 amplification according to subtype, with consistently high MDM2 amplification rates in GBC (up to 17.5%), and lower rates in CCA (up to 4.4%). The results from this literature review highlight the geographic heterogeneity of BTC and the need for standardised clinicopathologic assessment and reporting to allow cross-study comparisons.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296036","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}
Pub Date : 2024-09-17DOI: 10.1007/s11523-024-01096-3
Daniele Santini, Haoran Li, Giandomenico Roviello, Se Hoon Park, Enrique Grande, Jakub Kucharz, Umberto Basso, Ondrej Fiala, Fernando Sabino Marques Monteiro, Alexandr Poprach, Sebastiano Buti, Javier Molina-Cerrillo, Martina Catalano, Tomas Buchler, Emmanuel Seront, Jawaher Ansari, Zin W. Myint, Marwan Ghosn, Fabio Calabrò, Ray Manneh Kopp, Dipen Bhuva, Maria T. Bourlon, Michela Roberto, Mattia Alberto Di Civita, Veronica Mollica, Andrea Marchetti, Andrey Soares, Nicola Battelli, Marco Ricci, Ravindran Kanesvaran, Aristotelis Bamias, Camillo Porta, Francesco Massari, Matteo Santoni
Background
Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, “primary refractory” (Pref), face dismal outcomes.
Objective
Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref patients.
Methods
This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan–Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve.
Results
In our study, the Pref rate was 19%. Nivolumab/ipilimumab showed the highest Pref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-Pref patients (55.7 months), p < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for Pref patients with renal cell carcinoma. Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium risk, and no surgery and an increased risk of Pref. This study presents limitations, mainly because of its retrospective design.
Conclusions
The ARON-1 study provides valuable insights into Pref patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.
{"title":"Real-World Primary Resistance to First-Line Immune-Based Combinations in Patients with Advanced Renal Cell Carcinoma (ARON-1)","authors":"Daniele Santini, Haoran Li, Giandomenico Roviello, Se Hoon Park, Enrique Grande, Jakub Kucharz, Umberto Basso, Ondrej Fiala, Fernando Sabino Marques Monteiro, Alexandr Poprach, Sebastiano Buti, Javier Molina-Cerrillo, Martina Catalano, Tomas Buchler, Emmanuel Seront, Jawaher Ansari, Zin W. Myint, Marwan Ghosn, Fabio Calabrò, Ray Manneh Kopp, Dipen Bhuva, Maria T. Bourlon, Michela Roberto, Mattia Alberto Di Civita, Veronica Mollica, Andrea Marchetti, Andrey Soares, Nicola Battelli, Marco Ricci, Ravindran Kanesvaran, Aristotelis Bamias, Camillo Porta, Francesco Massari, Matteo Santoni","doi":"10.1007/s11523-024-01096-3","DOIUrl":"https://doi.org/10.1007/s11523-024-01096-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, “primary refractory” (<i>P</i><sub>ref</sub>), face dismal outcomes.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of <i>P</i><sub>ref</sub> patients.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan–Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In our study, the <i>P</i><sub>ref</sub> rate was 19%. Nivolumab/ipilimumab showed the highest <i>P</i><sub>ref</sub> rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-<i>P</i><sub>ref</sub> patients (55.7 months), <i>p</i> < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for <i>P</i><sub>ref</sub> patients with renal cell carcinoma. Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium risk, and no surgery and an increased risk of <i>P</i><sub>ref</sub>. This study presents limitations, mainly because of its retrospective design.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The ARON-1 study provides valuable insights into <i>P</i><sub>ref</sub> patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257954","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}