Targeted Oncology最新文献

{"title":"Real-World Outcomes of Adjuvant Pembrolizumab for Renal Cell Carcinoma: The Potential Role of PD-L1 as a Prognostic Biomarker.","authors":"Hiroki Ishihara, Takayuki Nakayama, Hironori Fukuda, Nanaka Katsurayama, Yuki Nemoto, Shinsuke Mizoguchi, Hiroaki Shimmura, Yasunobu Hashimoto, Atsuko Seki, Kazuhiko Yoshida, Junpei Iizuka, Tsunenori Kondo, Yoji Nagashima, Toshio Takagi","doi":"10.1007/s11523-026-01226-z","DOIUrl":"10.1007/s11523-026-01226-z","url":null,"abstract":"<p><strong>Background: </strong>Real-world data on adjuvant pembrolizumab after surgery for renal cell carcinoma (RCC) are limited.</p><p><strong>Objective: </strong>To clarify the real-world outcomes of adjuvant pembrolizumab for patients with RCC with a high risk of recurrence.</p><p><strong>Patients and methods: </strong>We retrospectively evaluated the clinicopathological data of 53 patients who received pembrolizumab as an adjuvant therapy after curative surgery for RCC on the basis of the criteria of the KEYNOTE-564 trial. The efficacy and safety profiles were assessed. The potential of PD-L1 expression as a biomarker of recurrence was evaluated in 35 RCC samples using the combined positive score (CPS).</p><p><strong>Results: </strong>The median follow-up period was 18.9 months. On the basis of the KEYNOTE-564 criteria, 45 patients (85%) were categorized into the intermediate-to-high-risk group. A total of 11 patients (21%) experienced recurrence, with a 12-month disease-free survival (DFS) rate of 90.5%. Patients with high PD-L1 CPS (≥ 10) had a higher recurrence rate than those with low PD-L1 CPS (< 10) (44% versus 5%, p = 0.0130). DFS was shorter in patients with high PD-L1 expression than in those with low PD-L1 expression (median: 24.0 months versus not reached, p = 0.0116). Grade ≥ 3 adverse events occurred in 13 patients (25%), and treatment discontinuation was required in 11 patients (21%).</p><p><strong>Conclusions: </strong>Adjuvant pembrolizumab exhibited feasible efficacy and manageable safety profiles for high-risk RCC in a real-world population. Further studies with longer follow-up periods and larger sample sizes are needed to confirm overall survival benefit, long-term toxicity, and the potential role of PD-L1 as a prognostic biomarker.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"559-567"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158192","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":"Plasma Biomarkers Associated with Clinical Outcomes of FOLFIRI Plus Ramucirumab in RAS Wild-Type Metastatic Colorectal Cancer: The JACCRO CC-16AR Trial.","authors":"Yu Sunakawa, Hisateru Yasui, Manabu Shiozawa, Hiroyuki Takeda, Naoya Akazawa, Tamotsu Sagawa, Kazuhiro Shiraishi, Takahisa Kyogoku, Takashi Mine, Yasuhiro Yuasa, Takanori Watanabe, Tatsuya Kinjo, Yoshihiro Okita, Hiroyuki Okuyama, Satoshi Yuki, Koki Miyakawa, Ayana Kobara, Shoko Yanaka, Yukiko Abe, Wataru Ichikawa, Masashi Fujii, Akihito Tsuji","doi":"10.1007/s11523-026-01223-2","DOIUrl":"10.1007/s11523-026-01223-2","url":null,"abstract":"<p><strong>Background: </strong>Second-line FOLFIRI plus ramucirumab (RAM) is one of standard treatments for metastatic colorectal cancer (mCRC) following progression on anti-EGFR therapy in RAS wild-type tumors. However, biomarkers for RAM efficacy remain unclear.</p><p><strong>Objective: </strong>We conducted a translational analysis to evaluate the association of plasma biomarkers, including angiogenesis-related factors (AFs) and RAS mutations in circulating tumor DNA (ctDNA), with clinical outcomes.</p><p><strong>Methods: </strong>This biomarker study was embedded within the JACCRO CC-16 trial, which enrolled patients with mCRC with RAS wild-type tumors receiving FOLFIRI plus RAM after anti-EGFR therapy. Plasma samples were collected at baseline, day 15, and post-treatment. RAS status in ctDNA was analyzed using BEAMing digital PCR; AFs were assessed using Luminex multiplex assay. Associations with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were analyzed.</p><p><strong>Results: </strong>Among 41 evaluable patients with RAS wild-type tumors, RAS mutations were detected in ctDNA at pretreatment in 44%. Patients without RAS mutations had significantly longer OS (28.1 versus 14.8 months; HR 0.30, p = 0.0008) and higher ORR (14.3% versus 5.6%). Elevated baseline interleukin-8 (IL-8) was associated with poorer OS (16.5 versus 32.2 months; HR 1.99, p = 0.049). IL-8 levels were significantly higher in patients with RAS mutations.</p><p><strong>Conclusion: </strong>RAS mutations in ctDNA and elevated IL-8 levels prior to second-line FOLFIRI plus RAM were associated with worse prognosis in mCRC. Moreover, our study demonstrated a significant association between RAS mutations and high IL-8 levels in this setting, suggesting a potential molecular-inflammatory interplay that contributes to resistance to VEGFR2 blockade.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"549-557"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975496","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":"Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.","authors":"Hendrik Schürmann, Wungki Park, Grainne M O'Kane, Carolina Sciortino, Monica Niger, Maximilian Reichert, Kenneth P Olive, Ina Pretzell, C Benedikt Westphalen","doi":"10.1007/s11523-026-01236-x","DOIUrl":"10.1007/s11523-026-01236-x","url":null,"abstract":"<p><p>For the past decades, chemotherapy constituted the therapeutic foundation in advanced or metastatic pancreatic cancer. Despite significant advances in the molecular understanding, translation into tangible patient benefit has remained modest. Until recently, mutant KRAS, the dominant oncogenic driver, was considered undruggable, and only a small subgroup of patients potentially benefited from targeted therapies. With the emergence of KRAS inhibitors, most patients with pancreatic cancer in theory qualify for targeted therapeutics. Final results from the RASolute 302 trial showed clinically meaningful activity of RAS inhibition in patients with metastatic pancreatic cancer and paved the way for approval. Ongoing preclinical and coclinical studies have documented both intrinsic and acquired mechanisms of resistance to KRAS inhibition. Given the cellular plasticity seen in pancreatic cancer, the identification and anticipation of resistance mechanisms will be critical to exploit emerging therapeutic vulnerabilities through novel combination strategies. In view of the increasing number of trials and the growing body of evidence for targeted therapies, pancreatic cancer is entering a transitional phase in which precision oncology strategies must be redefined beyond rare molecular subgroups. In this review, we will briefly revisit targeted therapeutic approaches in pancreatic cancer to then discuss the clinical implications of genomic and transcriptomic heterogeneity in KRAS-mutant and KRAS wild-type disease. We will outline how our expanding biological insights into pancreatic cancer could inform combination and sequential therapeutic approaches.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"521-540"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Epidemiology and Real-World Outcomes in Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Mutant Non-small Cell Lung Cancer by Region: A Targeted Literature Review.","authors":"Koichi Goto, Hidetoshi Hayashi, Sonia S Maruti, Heiko Zettl, Lalith Mittal, Smit Pathak, Xiuning Le","doi":"10.1007/s11523-026-01229-w","DOIUrl":"10.1007/s11523-026-01229-w","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"613-615"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Real-World Outcomes of Sequential Afatinib and Osimertinib Versus Afatinib and Chemotherapy in EGFR-Mutant NSCLC: Taiwan Multicenter GIANT Study.","authors":"How-Wen Ko, Ying-Ting Liao, Sheng-Kai Liang, Yen-Hsiang Huang, Yu-Ching Lin, Ping-Chi Liu, Chin-Chou Wang, Jeng-Shiuan Tsai, Yuh-Min Chen, Jin-Yuan Shih, Tsung-Ying Yang, Cheng-Ta Yang","doi":"10.1007/s11523-026-01216-1","DOIUrl":"10.1007/s11523-026-01216-1","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"609-612"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781796","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":"Efficacy and Safety Differences Between Abiraterone and Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-analysis of Real-World Studies.","authors":"Anikó Katalin Valikovics, Dániel Bacsó, Nadeen Samaien, Isabel Pinto Amorim das Virgens, Boglárka Szentes, Gergely Agócs, Mahmoud Obeidat, Tamás Széll, Boris Hadaschik, Péter Hegyi, Péter Nyirády, Tibor Szarvas","doi":"10.1007/s11523-026-01230-3","DOIUrl":"10.1007/s11523-026-01230-3","url":null,"abstract":"<p><strong>Background: </strong>Abiraterone (ABI) and enzalutamide (ENZA) are standard treatments for metastatic castration-resistant prostate cancer (mCRPC). However, their safety and efficacy have not been directly compared in prospective clinical trials.</p><p><strong>Objective: </strong>To directly compare their safety and efficacy in prospective clinical trials.</p><p><strong>Patients and methods: </strong>A systematic search was performed in PubMed, Embase, and Cochrane Library databases (CRD42024608496) on 24 June 2025. Eligibility criteria included studies on patients with mCRPC treated with ABI or ENZA reporting outcomes such as overall survival (OS), prostate-specific antigen (PSA) response (PSA50/90), progression-free survival (rPFS/bPFS), and rates of grade ≥ 3 adverse events, dose reduction, treatment discontinuation, and major cardiovascular events (MACE). Both first- and second-line mCRPC treatment settings were considered. The inverse variance method was used to calculate pooled hazard ratios (HRs), using the natural logarithm of the HR and its standard error (SE) from the available data.</p><p><strong>Results: </strong>A total of 47 real-world observation studies and data from 71,984 patients were included, with no randomized controlled trials available for direct comparison. ENZA proved more effective in terms of PSA50 (odds ratio (OR): 1.82; 95% confidence interval (CI): 1.38-2.4) and OS (HR: 0.79; 95% CI 0.71-0.87) in the overall cohort as well as in the first-line (PSA50: OR: 1.69; 95% CI 1.23-2.31, OS: HR: 0.85, 95% CI 0.79-0.92) and second-line setting (PSA50 OR: 1.78; 95% CI 1.23-2.58, OS: HR: 0.69; 95% CI 0.60-0.80). However, grade ≥ 3 AEs and treatment discontinuation rates were significantly more frequent with ENZA (OR: 2.17; 95% CI 0.85-5.54 and OR: 1.81; 95% CI 1.45-2.25, respectively), while MACE rates were lower (OR: 0.53; 95% CI 0.33-0.84).</p><p><strong>Conclusions: </strong>ENZA showed greater efficacy, whereas serious AEs were less frequent with ABI. However, this difference may decrease or even disappear upon switching these therapies. Therefore, individual decision-making is encouraged, balancing efficacy and safety. ENZA should be prioritized if OS is the main goal, whereas ABI may be preferred when minimizing AEs is important. ENZA is also associated with a lower risk of MACE.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"507-520"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346166","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":"Real-World Comparative Effectiveness and Safety of Immune Checkpoint Inhibitors in Advanced Renal Cell Carcinoma: A Systematic Review.","authors":"Chin Hang Yiu, Gwyneth Yuet Yin Leung, Isabelle C Lee, Christine Y Lu","doi":"10.1007/s11523-026-01227-y","DOIUrl":"10.1007/s11523-026-01227-y","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI)-based regimens are the standard first-line therapy for advanced renal cell carcinoma (RCC). However, their comparative effectiveness and safety in routine clinical practice remain incompletely characterised.</p><p><strong>Objective: </strong>The aim of this study was to systematically synthesise comparative real-world evidence on the efficacy and safety of ICI-based regimens in patients with advanced RCC.</p><p><strong>Methods: </strong>A systematic search of MEDLINE, Embase, and Scopus was conducted from database inception to 21 January 2026, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Observational cohort studies evaluating ICI-based regimens in advanced RCC with an active comparator were included. Primary efficacy outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Safety outcomes included treatment-related adverse events. Study quality was assessed using the Newcastle-Ottawa Scale, with efficacy and safety evaluated separately. Owing to substantial clinical and methodological heterogeneity, findings were synthesised narratively.</p><p><strong>Results: </strong>Overall, 58 retrospective cohort studies comprising 35,215 patients were included. Most studies evaluated first-line therapy and involved populations with mixed histology and heterogeneous prognostic risk profiles. Overall, ICI-tyrosine kinase inhibitor (TKI) combinations were generally associated with more favourable survival outcomes compared with dual ICI therapy or TKI monotherapy, with the most consistent benefit observed for PFS. Evidence comparing dual ICI therapy with TKI monotherapy was mixed, with most studies reporting no statistically significant differences in survival outcomes. Comparative safety data were limited, with the majority of studies relying on unadjusted descriptive analyses, limiting robust comparative interpretation of safety outcomes.</p><p><strong>Conclusions: </strong>Real-world evidence suggests that ICI-TKI combinations are associated with more favourable survival outcomes compared with other treatment options in advanced RCC, while the comparative effectiveness of dual ICI therapy versus TKI monotherapy remains inconclusive. Substantial heterogeneity and methodological limitations, particularly in safety reporting, limit definitive interpretation. High-quality real-world studies incorporating robust confounding adjustment and clinically relevant subgroup analyses are needed to better inform treatment selection in routine practice.</p><p><strong>Trial registry: </strong>International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD420251149614.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"475-506"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101887","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":"Chimeric Antigen Receptor-T Cell Therapy for Pediatric and Young Adult Primary Central Nervous System Tumors: A Systematic Review of Early Phase Clinical Trials with a Focus on Diffuse Midline Glioma.","authors":"Sai Sanikommu, Alejandro N Santos, Bashar Dawoud, Khushi H Shah, Sima Vazquez, Ashish H Shah, Victor M Lu","doi":"10.1007/s11523-026-01225-0","DOIUrl":"10.1007/s11523-026-01225-0","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor (CAR)-T cell therapy has demonstrated substantial efficacy in hematologic malignancies; however, its application in pediatric and young adult primary central nervous system (CNS) tumors, particularly pediatric diffuse midline glioma (DMG), remains investigational. Several early phase trials have recently reported clinical experiences with CNS-directed CAR-T cell therapies, necessitating a systematic distillation to better understand the state of the field.</p><p><strong>Objective: </strong>The aim of the study was to systematically review early phase clinical evidence evaluating the safety, feasibility, and preliminary efficacy of CAR-T cell therapy in pediatric and young adult patients with primary CNS tumors.</p><p><strong>Patients and methods: </strong>A systematic review was conducted on early phase clinical studies assessing CAR-T cell therapies in pediatric and young adult patients diagnosed with primary brain tumors. Data collected included information on antigen targets, route of administration, dosing strategies, patient characteristics, prior therapies, toxicity profiles, anti-inflammatory management, radiographic and clinical outcomes, biologic correlates, and survival.</p><p><strong>Results: </strong>The search identified eight early phase trials involving 74 pediatric and young adult patients. Of the cohort, 63 received CAR-T cell infusion, targeting B7-H3, GD2, HER2, EGFR806, and PSMA-GD2 via intraventricular, intravenous, or combined routes. All patients had heavily pretreated, recurrent, or refractory disease, with all DMG cohorts receiving prior radiation. CAR-T cell therapy was feasible, with no treatment-related mortality. Immune toxicities, including cytokine release syndrome and CNS neurotoxicity, were common but reversible with corticosteroids and cytokine therapies. Among response-evaluable patients, 65% achieved disease control (stable disease or partial response), while 35% had progressive disease. Objective responses were rare, but many had disease stabilization, especially in DMG cohorts. Post-infusion, immune activation was evident, with CAR-T cell trafficking to CNS and increased cytokines in cerebrospinal fluid and plasma. Median survival ranged from 13 to over 30 months, with some patients exceeding expectations.</p><p><strong>Conclusions: </strong>Preliminary clinical experience indicates that CAR-T cell therapy for pediatric and young adult CNS tumors is biologically active and clinically feasible, exhibiting a distinct yet manageable toxicity profile. Although durable objective responses are currently limited, the frequent occurrence of disease stabilization and extended survival in certain patients substantiate ongoing research and the refinement of CAR-T cell strategies for CNS malignancies.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"459-474"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253326","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":"Afatinib Versus Osimertinib as First-Line Treatment for Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A 3-Year Follow-Up Overall Survival Analysis.","authors":"Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, I-Hung Lin, Mu-Han Peng, Tsung-Ying Yang","doi":"10.1007/s11523-026-01224-1","DOIUrl":"10.1007/s11523-026-01224-1","url":null,"abstract":"<p><strong>Background: </strong>To date, there are limited clinical trials comparing the clinical efficacy between second-generation and third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI)s.</p><p><strong>Objective: </strong>The objective of this study was to compare the survival outcomes between afatinib and osimertinib as first-line treatments in patients with advanced EGFR-mutant non-small-cell lung cancer (NSCLC).</p><p><strong>Patients and methods: </strong>Between January 2018 and December 2020, we retrospectively enrolled patients with advanced NSCLC harboring an exon 19 deletion or L858R mutation who received afatinib or osimertinib as first-line treatment to analyze the progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>A total of 128 patients were included in this study, with 81 in the afatinib group and 47 in the osimertinib group. The median follow-up time was 39.9 months for the afatinib group and 37.0 months for the osimertinib group. The median PFS was 13.5 months in the afatinib group and 18.2 months in the osimertinib group (p = 0.240). The median OS was 40.5 months in the afatinib group and 37.0 months in the osimertinib group (p = 0.980). A total of 63% of patients received osimertinib as sequential therapy following progression on afatinib, with a median OS of 41.7 months. Among these patients, the median OS was 41.7 months for those with a detected T790M mutation, 42.0 months for those without the mutation, and 35.6 months for those with unknown T790M mutation status.</p><p><strong>Conclusions: </strong>Our study demonstrated that both afatinib and osimertinib as first-line treatments offer favorable median OS in patients with advanced EGFR-mutant NSCLC. In addition, we recommend that patients receiving afatinib as first-line therapy undergo sequential osimertinib treatment, regardless of their T790M mutation status.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"581-591"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199840","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":"From Recommendation to Implementation: Clinical Outcomes of a Single-Center Molecular Tumor Board.","authors":"Tabea Fröhlich, Ulrich Lehmann, Tanja Reineke-Plaaß, Thomas Wirth, Sabrina Welland, Chen Du, Bernd Auber, Benjamin-Alexander Bollmann, Philipp Ivanyi, Tjoung-Won Park-Simon, Diana Steinmann, Christian Hartmann, Ariana de Oliviera Mekonnen, Anja Heutling, Andrea Schütte, Hans Heinrich Wedemeyer, Florian Heinrich Heidel, Susanne Isfort, Arndt Vogel, Anna Saborowski","doi":"10.1007/s11523-026-01231-2","DOIUrl":"10.1007/s11523-026-01231-2","url":null,"abstract":"<p><strong>Background: </strong>Molecular tumor boards (MTBs) support precision oncology by translating genomic profiling into evidence-based treatment recommendations, for example according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT). Their clinical utility in real-world care depends on effective implementation within healthcare systems.</p><p><strong>Objectives: </strong>To evaluate the implementation rate of MTB recommendations, associated determinants, and clinical outcomes in a real-world single-center cohort.</p><p><strong>Patients and methods: </strong>At a single-center MTB, 582 consecutive cases (2020-2023) were retrospectively analyzed, with last survival follow-up in August 2025. Patient demographics, tumor characteristics, genomic alterations, ESCAT and ZPM (Zentrum für Personalisierte Medizin) evidence levels, targeted therapy recommendation and implementation rates, survival outcomes, and barriers to implementation were evaluated using descriptive and inferential statistics, as appropriate.</p><p><strong>Results: </strong>Of 582 patients (median age 61 years, 48.5% female, 78.2% UICC stage IV), 55.6% (n = 324) received a targeted therapy recommendation, most based on ESCAT I-II evidence (59.9%). Among patients with a therapy recommendation, implementation status was unknown in 83 cases, but at least 23.5% (n = 76) received the proposed therapy. Major barriers included continuation of alternative systemic therapy (n = 89, 53.9%) and best supportive care or death before initiation (n = 54, 32.7%). Stronger levels of evidence (ESCAT per level increase: OR 1.22, 95% CI 1.08-1.39, p = 0.003; ZPM per level increase: OR 1.43, 95% CI 1.19-1.75, p < 0.001) and lower gastrointestinal cancer (OR 2.39, 95% CI 1.13-4.93, p = 0.020) were positively associated with increased likelihood of therapy implementation, while extramural molecular profiling showed a trend toward lower uptake (OR 0.61, 95% CI 0.36-1.03, p = 0.062). Overall survival (OS) from the date of MTB discussion in the full cohort (n = 563) was 11.1 months (95% CI 9.7-12.8). In patients who received at least one prior therapy before MTB discussion (n = 202), OS was 20.1 months (95% CI 12.3-NA) in patients who received the MTB-recommended therapy (n = 62) versus 7.7 months (95% CI 6.5-12.5) in those who did not (n = 140; p < 0.001). Among 31 patients with paired data, PFS under MTB-guided therapy was significantly longer than in the prior line (p = 0.036), with 54.8% achieving a PFS2/PFS1 ratio ≥ 1.3.</p><p><strong>Conclusions: </strong>In this real-world analysis, implementation of MTB recommendations was associated with improved survival outcomes. However, systemic, clinical, and logistical barriers substantially limited uptake. Earlier integration of MTBs into treatment planning and targeted strategies to address these barriers may help increase their potential benefit for patients.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"593-608"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472876","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}