Targeted Oncology最新文献

{"title":"Durvalumab Following Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Differences in Survival Based on Age and Post-Progression Systemic Therapy.","authors":"Doran Ksienski, Pauline T Truong, Jeffrey N Bone, Sarah Egli, Melissa Clarkson, Tiffany Patterson, Mary Lesperance, Suganija Lakkunarajah","doi":"10.1007/s11523-024-01111-7","DOIUrl":"10.1007/s11523-024-01111-7","url":null,"abstract":"<p><strong>Background: </strong>Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC).</p><p><strong>Objectives: </strong>The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy.</p><p><strong>Patients and methods: </strong>Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively. Progression-free survival (PFS) and overall survival (OS) from ICI start were analyzed in three cohorts aged < 65, 65-74, and ≥ 75 years. Multivariable Cox proportional hazard regression modelling of factors associated with OS was undertaken. Logistic regression analysis identified risk factors of early durvalumab discontinuation for toxicity. Time from first salvage drug treatment to death (OS-2) was described.</p><p><strong>Results: </strong>A total of 472 patients were analyzed: the proportions aged < 65, 65-74, and ≥ 75 years were 34.3%, 42.8%, and 22.9%, respectively. Odds of early durvalumab discontinuation was 2.2-fold greater in the oldest (versus youngest) cohort. Age associated differences in median PFS (26.7 months, 20.3 months, and 14.2 months; p < 0.001) and OS (60.8 months, 44.4 months, and 27.6 months; p < 0.001) were observed. On multivariable analysis, factors associated with shorter OS were age ≥ 75 years (versus < 65), performance status 2/3 (versus 0/1), stage IIIC (versus IIIA), neutrophil to lymphocyte ratio (per 7.43 unit increase), Charlson comorbidity index (per 1 unit increase), tumoral PD-L1 expression < 1% (versus ≥ 50%, 1-49%, or unknown), and squamous histology (versus non-squamous). Of 264 patients with disease progression, 48.5% received subsequent drug therapy. Median OS-2 was longer with ICI alone (9.9 months) or ICI-chemotherapy (11.8 months) than platinum doublet chemotherapy (6.7 months.) For recurrences < 6 months from the last durvalumab infusion, OS-2 were similar across treatment groups.</p><p><strong>Conclusions: </strong>In the studied cohort, OS was significantly shorter for patients ≥ 75 years of age treated with cCRT followed by durvalumab compared to those < 65 years. Post-progression systemic therapy was associated with modest efficacy, underscoring the need for new therapies.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"149-160"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569684","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":"Delayed Separation of Kaplan-Meier Curves is Commonly Observed in Studies of Advanced/Metastatic Solid Tumors Treated with Anti-PD-(L)1 Therapy: Systematic Review and Meta-Analysis.","authors":"Do-Youn Oh, Nana Rokutanda, Magdalena Żotkiewicz, Philip He, Jennifer Stocks, Melissa L Johnson","doi":"10.1007/s11523-024-01108-2","DOIUrl":"10.1007/s11523-024-01108-2","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI) Kaplan-Meier (KM) curves often show delayed survival benefit followed by long-term survival in a subgroup of patients. Such outcomes can violate the proportional hazards assumption, leading to a loss of statistical power.</p><p><strong>Objective: </strong>We aimed to determine common trends in delayed separation to inform future ICI clinical trials.</p><p><strong>Patients and methods: </strong>A literature search was performed using Trialtrove^® to identify phase III trials of antiprogrammed cell death (ligand)-1 (anti-PD-[L]1) agents in locally advanced/metastatic solid tumors published between January 2010 and September 2021. The frequency of delayed separation of overall survival (OS) and progression-free survival (PFS) KM curves, correlation between duration of delayed separation in OS/PFS KM curves, and correlation between duration of delayed separation in OS/PFS KM curves with corresponding hazard ratios (HRs) were assessed in all-comer and PD-L1 enriched populations.</p><p><strong>Results: </strong>Eighty-five studies with OS/PFS KM curves were identified. Most studies showed delayed separation of OS (> 67.9%) and PFS (> 54.5%) KM curves. The correlation between the duration of delayed separation in OS/PFS KM curves was strongest in the PD-L1 enriched population (adjusted R² = 0.66). No correlation was seen between the duration of delayed separation of OS KM curves and OS HR. A modest correlation was seen between the duration of delayed separation of PFS KM curves and PFS HR in all-comer and PD-L1 enriched populations (adjusted R² = 0.24 and 0.31, respectively).</p><p><strong>Conclusions: </strong>Delayed separation of KM curves was common in clinical trials of anti-PD-(L)1 agents. Understanding delayed separation is key to clinical study designs and assessing outcomes with ICIs.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"45-56"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628716","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":"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":"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":" ","pages":"925-939"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557658/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"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":" ","pages":"981-990"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557715/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"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":" ","pages":"823-832"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557660/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enfortumab Vedotin Following Platinum Chemotherapy and Avelumab Maintenance in Patients with Metastatic Urothelial Carcinoma: A Retrospective Data from the ARON-2^EV 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":"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^EV 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":" ","pages":"905-915"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557677/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s11523-024-01112-6","DOIUrl":"10.1007/s11523-024-01112-6","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"819-822"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591141","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 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":"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":" ","pages":"917-923"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","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}

{"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":"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":" ","pages":"957-964"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","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}

{"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":"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":" ","pages":"941-955"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","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}