Targeted Oncology最新文献

{"title":"Subcutaneous Amivantamab and Lazertinib in PALOMA-3: Efficacy, Safety, and Administration: A Vodcast.","authors":"Danny Nguyen","doi":"10.1007/s11523-026-01248-7","DOIUrl":"10.1007/s11523-026-01248-7","url":null,"abstract":"<p><p>Intravenous (IV) amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, is approved for multiple indications alone or in combination for patients with EGFR-mutated advanced or metastatic nonsmall cell lung cancer (NSCLC). In the PALOMA-3 study, subcutaneous (SC) amivantamab was investigated to improve tolerability, reduce administration time, maintain efficacy, and improve patient experience. This vodcast reviews the rationale and data supporting SC amivantamab on the basis of the PALOMA-3 study and provides expert-led recommendations for SC amivantamab treatment. The PALOMA-3 study investigated the noninferiority of pharmacokinetics, with other endpoints including efficacy and safety of SC versus IV amivantamab, combined with lazertinib in participants with EGFR-mutated, advanced NSCLC after disease progression on osimertinib and platinum-based chemotherapy. Geometric mean ratios of C_trough for SC to IV amivantamab were 1.15 at Cycle 2 Day 1 (C2D1) and 1.42 at C4D1; C2_AUCD1-D15 was 1.035. Objective response rate (ORR) was 30% in the SC group and 33% in the IV group; median progression-free survival was 6.1 and 4.3 months, respectively. SC amivantamab resulted in fewer patients reporting infusion-related reactions (IRR; 13% versus 66% IV) and venous thromboembolism (VTE; 9% versus 14%) with prophylactic anticoagulation; shorter administration time at C1D1 (< 5 min per SC injection versus ~ 5 h for IV); and higher patient-reported convenience at the end of treatment (85% versus 35%). We discuss clinical considerations for SC amivantamab dosing and administration, including premedications, prophylactic measures, dose modifications, management of adverse reactions, and switching between IV and SC amivantamab. In conclusion, SC amivantamab demonstrated noninferior pharmacokinetics and antitumor responses compared with IV amivantamab in the PALOMA-3 study. SC amivantamab also reduced IRR and VTE, with shorter treatment administration times and enhanced patient convenience compared with IV. Utilizing SC amivantamab, while optimizing treatment efficacy and safety through mitigating and managing adverse events, may enhance the patient experience.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"617-620"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680045","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":"Risk of Recurrence in Patients with HR+/HER2- Early Breast Cancer: A Podcast.","authors":"Maryam B Lustberg, Megan-Claire Chase, Stacey Tinianov, Kevin Kalinsky","doi":"10.1007/s11523-026-01241-0","DOIUrl":"10.1007/s11523-026-01241-0","url":null,"abstract":"<p><p>Within 20 years of diagnosis, up to 27% of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer will experience recurrence, despite standard-of-care treatments. Of these recurrences, approximately half will occur within 5 years of diagnosis, regardless of disease stage or nodal status. The majority of recurrences are metastatic, for which there is currently no cure. Patients may not fully discern the incurable and potentially distant nature of disease recurrences, or they may be unaware the risk of recurrence exists. Gaps remain in awareness, understanding, and communication around recurrence risk between healthcare professionals and patients. Thus, in addition to understanding the clinical trial and real-world data on recurrences, it is also important to amplify the patient perspective on the impact of recurrence risk to facilitate effective shared decision making. This podcast will bring together physician and patient advocate experts to discuss the risk of recurrence for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer including early and late risk of recurrence, discuss how risk is assessed, and examine the evolving treatment landscape for reducing risk. Supplementary file1 (MP4 310486 KB).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"643-651"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866395","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":"One-Week Inflammatory Kinetics After First-Line Nivolumab Plus Ipilimumab in Metastatic Renal Cell Carcinoma: A Multicenter Landmark Analysis.","authors":"Toru Inoue, Kazuyuki Numakura, Takahiro Osawa, Sei Naito, Takuma Ishihara, Kojiro Ohba, Kosuke Ueda, Yuya Sekine, Masaharu Oki, Hirohito Naito, Haruka Miyata, Hiroshi Kikuchi, Shin Kobayashi, Shintaro Narita, Norihiko Tsuchiya, Mikio Sugimoto, Tsukasa Igawa, Toshitaka Shin","doi":"10.1007/s11523-026-01251-y","DOIUrl":"10.1007/s11523-026-01251-y","url":null,"abstract":"<p><strong>Background: </strong>First-line nivolumab plus ipilimumab can produce durable survival in metastatic renal cell carcinoma, yet some patients experience early progression or rapid clinical deterioration before first scheduled imaging. Because radiologic response assessment is typically unavailable until approximately 12 weeks, clinically accessible signals during this pre-imaging interval are needed.</p><p><strong>Objective: </strong>We aimed to evaluate whether early changes in blood-based inflammatory biomarkers at predefined post-treatment landmarks were associated with overall survival and to determine which biomarker showed the most consistent early prognostic signal.</p><p><strong>Methods: </strong>In this multicenter retrospective cohort study across eight Japanese institutions, 219 patients with metastatic renal cell carcinoma treated with first-line nivolumab plus ipilimumab were analyzed. Predefined landmark analyses at 1 week, 1 month, and 3 months compared six blood-based inflammatory biomarkers using restricted cubic splines with multiple imputation. Overall survival was the primary endpoint.</p><p><strong>Results: </strong>The 1-week landmark showed the most consistent association with overall survival. Among six biomarkers, change in pan-immune-inflammation value showed the most reproducible pattern. Among 183 patients with paired baseline and 1-week pan-immune-inflammation value data, PIV-BOOST, defined as any pan-immune-inflammation value increase (> 0%) from baseline, was observed in 110 patients (60.1%) and was independently associated with improved overall survival (adjusted hazard ratio 0.60, 95% confidence interval 0.39-0.92; p = 0.018).</p><p><strong>Conclusions: </strong>One-week inflammatory kinetics provided early prognostic information before first scheduled imaging in first-line nivolumab plus ipilimumab-treated metastatic renal cell carcinoma. A simple direction-of-change rule for pan-immune-inflammation value may complement baseline risk assessment; however, prospective external validation is required before clinical implementation.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"749-759"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971478","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":"Summary of Research: HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination with Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer.","authors":"Veronique Dieras, Giuseppe Curigliano, Miguel Martin, Florence Lerebours, Junji Tsurutani, Marie-France Savard, Katarzyna J Jerzak, Xichun Hu, Ciara C O'Sullivan, Eriko Tokunaga, Alicia Okines, Chiun-Sheng Huang, William Jacot, Joohyuk Sohn, Eduardo Cronemberger Silva, Volkmar Mueller, Shan Yang, Giovanna Granata, Qi Shen, Erika Hamilton","doi":"10.1007/s11523-026-01245-w","DOIUrl":"10.1007/s11523-026-01245-w","url":null,"abstract":"<p><p>This is a summary of a research article reporting the findings of the HER2CLIMB-05 trial (NCT05132582), a randomized, double-blind, placebo-controlled, international, phase III trial. The HER2CLIMB-05 trial was conducted to compare the efficacy and safety of adding tucatinib versus placebo to first-line maintenance therapy (trastuzumab and pertuzumab) following induction chemotherapy, in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. The key finding of the HER2CLIMB-05 trial was that progression-free survival was significantly improved in the tucatinib arm over the control arm (24.9 vs 16.3 months). The safety profile of tucatinib plus maintenance therapy was consistent with the known toxicities of each individual drug. The HER2CLIMB-05 regimen, with its high efficacy and manageable toxicity, represents a valuable option for first-line maintenance therapy in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"653-656"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008835","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":"Baseline Disease Characteristics and Platinum Sensitivity as Predictors of Outcomes in Sequential Therapy with Platinum-Based Chemotherapy, Avelumab Maintenance, and Enfortumab Vedotin in Advanced Urothelial Carcinoma (ARON-2EV Study).","authors":"Mimma Rizzo, Sebastiano Buti, Ondřej Fiala, Lorena Incorvaia, Javier Molina-Cerrillo, Maria T Bourlon, Wataru Fukuokaya, Fumihiko Urabe, Se Hoon Park, Karl Mayrhofer, Renate Pichler, Dora Niedersuess-Beke, Tarek Taha, Thomas Büttner, Aristotelis Bamias, Emmanuel Seront, Daniele Santini, Luciano Stumbo, Alejo Rodriguez-Vida, Francesco Massari, Fernando Sabino Marques Monteiro, Andrey Soares, Enrique Grande, Matteo Santoni","doi":"10.1007/s11523-026-01238-9","DOIUrl":"10.1007/s11523-026-01238-9","url":null,"abstract":"<p><strong>Background: </strong>Numerous case series have corroborated the efficacy of the first-line approach of platinum-based chemotherapy and avelumab maintenance followed by enfortumab vedotin monotherapy (PBC-AM-EV) in real-world patients with advanced urothelial carcinoma.</p><p><strong>Objective: </strong>The present investigation aimed to characterize the baseline clinical and pathological characteristics and outcomes of the PBC-AM-EV treatment sequence in the advanced urothelial carcinoma population.</p><p><strong>Methods: </strong>ARON-2^EV is a global retrospective study investigating the real-world use of EV in patients with advanced urothelial carcinoma. Two hundred and three patients receiving PBC-AM-EV were analyzed. Primary endpoints were disease response, therapy sequence duration, and overall survival. Secondary objectives included the evaluation of clinical factors associated with outcomes. Patient characteristics were analyzed using descriptive statistics; overall survival and therapy sequence duration were estimated using the Kaplan-Meier method and assessed with log-rank tests and Cox proportional hazards models.</p><p><strong>Results: </strong>Following a median follow-up of 23.1 months, the median overall survival from PBC initiation was 31.6 months, with a 2-year overall survival rate of 68%. Survival outcomes were consistent across most clinicopathologic subgroups, but were significantly influenced by Eastern Cooperative Oncology Group performance status, prior response to PBC, and cisplatin-based regimens. Median therapy sequence duration was 26.5 months and was prolonged in patients with exclusive nodal metastases and cisplatin exposure. A 43% objective response rate was achieved by EV, including durable disease control, particularly among patients who benefited from prior PBC and avelumab maintenance.</p><p><strong>Conclusions: </strong>The PBC-AM-EV sequence demonstrates sustained real-world efficacy, with outcomes driven by baseline characteristics, platinum responsiveness, and preserved EV activity irrespective of prior immunotherapy response.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"775-784"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621418","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":"Clinical Pharmacology of Lisocabtagene Maraleucel in B-cell Malignancies.","authors":"Ken Ogasawara, Rina Nishii, Yizhe Chen, Nanda Balasubramanian, Abood Okal","doi":"10.1007/s11523-026-01246-9","DOIUrl":"10.1007/s11523-026-01246-9","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapies represent a distinct therapeutic modality whose clinical activity is governed by in vivo cellular kinetics. Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed, 4-1BB CAR T-cell product in which in vivo expansion plays an important role in clinical pharmacology assessments. Across B-cell malignancies, characterization of liso-cel cellular kinetics demonstrates substantial interindividual variability in expansion, with no single evaluated clinical covariate exerting a clinically meaningful effect. Higher in vivo expansion has been associated with both efficacy and safety outcomes; however, interpretation of these relationships requires careful consideration of end point selection, baseline confounding, and outcome-specific biological context. Particularly, expansion-efficacy relationships are associative rather than causal and are influenced by baseline clinical characteristics and how efficacy end points are defined and assessed. Expansion-safety relationships are end point-dependent, reflecting dynamic immune interactions in the setting of cytokine release syndrome and predominantly downstream toxicity for neurological events. Other clinical pharmacology considerations, including retreatment, persistence, B-cell aplasia, and immunogenicity, further inform the interpretation of liso‑cel expansion within a broader clinical and biological framework. Collectively, these findings indicate that assessing in vivo liso-cel expansion provides important contextual clinical pharmacology information but does not establish it as an independent or deterministic driver of clinical outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"669-679"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797759","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":"Changing Treatment Landscape of Hepatocellular Carcinoma: A Real-World Retrospective Analysis of Treatment Algorithms and Outcomes of Patients over 10 Years.","authors":"Melanie Bathon, Nele Binder, Sabrina Welland, Christoph Gerdes, Thomas Wirth, Kristina I Ringe, Markus Quante, Arndt Vogel, Anna Saborowski","doi":"10.1007/s11523-026-01239-8","DOIUrl":"10.1007/s11523-026-01239-8","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma is one of the most common cancers worldwide and the third leading cause of cancer-related mortality. The therapeutic landscape of hepatocellular carcinoma, especially systemic therapies, is constantly changing and characterized by a multimodal approach.</p><p><strong>Objective: </strong>The aim of this study was to investigate whether and how treatment sequencing according to tumor stage and liver function has changed over time and if the introduction of new therapeutic options has led to improved survival rates.</p><p><strong>Methods: </strong>Therapy concepts were retrospectively recorded and evaluated in a cohort of 1288 patients with hepatocellular carcinoma with a first diagnosis between January 2013 and December 2022 who were divided into two cohorts with a cut-off for dividing in 2020 owing to the approval of atezolizumab and bevacizumab for the treatment of hepatocellular carcinoma by the European Medicines Agency (Cohort A initial diagnosis 2013-19, Cohort B initial diagnosis 2020-22). All patients were treated at Hannover Medical School, Germany.</p><p><strong>Results: </strong>Baseline characteristics differed significantly between cohorts, with Cohort B presenting at earlier tumor stages and with better preserved liver function. Across all treatment modalities, liver function emerged as the primary determinant of prognosis, independent of tumor stage and performance status. Over time, a treatment shift from transarterial chemoembolization towards systemic therapies was observed. Median overall survival from initial diagnosis did not differ between cohorts. In unadjusted analyses, patients treated with immune checkpoint inhibitor-based regimens demonstrated longer median overall survival compared with those receiving tyrosine kinase inhibitors. However, after multivariable adjustment for baseline imbalances, no independent survival difference between treatment groups remained.</p><p><strong>Conclusions: </strong>This study provides a detailed longitudinal assessment of evolving treatment patterns and outcomes, highlighting a clear shift in therapeutic strategies over time with the increasing adoption of systemic therapies. Despite evolving treatment strategies and increased use of systemic therapies, liver function remained the dominant prognostic factor across treatment settings. Observed survival differences between treatment modalities were strongly influenced by baseline patient characteristics and treatment selection.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"785-797"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593128","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":"Claudin-18.2 in Gastric and Gastroesophageal Junction Adenocarcinoma: From Biology to Therapeutic Targeting: A Narrative Review.","authors":"Robin Grellet, Paul Rat, Olivier Facy, Nicolas Santucci","doi":"10.1007/s11523-026-01247-8","DOIUrl":"10.1007/s11523-026-01247-8","url":null,"abstract":"<p><p>Gastric and gastroesophageal junction adenocarcinoma remains associated with a poor prognosis despite recent therapeutic advances. Claudin-18.2, a tight junction protein normally restricted to gastric epithelial cells, has emerged as a clinically validated and therapeutically actionable biomarker due to its preserved expression and aberrant membrane accessibility in malignant tissues. We conducted a narrative review of the literature (PubMed/MEDLINE and ClinicalTrials.gov; January 2000-December 2025) to summarize current knowledge on Claudin-18.2 biology, expression patterns, clinical relevance, and therapeutic targeting in gastric and gastroesophageal junction adenocarcinoma. Claudin-18.2 is frequently retained in gastric and gastroesophageal junction adenocarcinoma and can be reliably assessed using standardized immunohistochemistry. The phase III SPOTLIGHT and GLOW trials demonstrated that zolbetuximab significantly improves progression-free survival and overall survival when combined with first-line chemotherapy in Claudin-18.2-positive (moderate [2+] to strong [3+] membranous staining in ≥ 75% of tumor cells), human epidermal growth factor receptor 2-negative advanced disease. Emerging strategies, including antibody-drug conjugates, bispecific antibodies, and chimeric antigen-T-cell therapies, are under active investigation. Claudin-18.2 has established itself as a validated therapeutic target in gastric and gastroesophageal junction adenocarcinoma. Its integration into clinical practice reflects a shift toward biomarker-driven, multi-target treatment algorithms, although challenges remain regarding assay standardization, resistance mechanisms and optimal therapeutic sequencing alongside human epidermal growth factor receptor 2, microsatellite instability/deficient mismatch repair, and programmed death-ligand 1.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"721-733"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761583","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":"FGF/FGFR Alteration Type as a Candidate Enrichment Biomarker for Gunagratinib in Recurrent or Metastatic Head and Neck Cancer: An Exploratory Analysis of Two Early-Phase Trials.","authors":"Liqiong Xue, Guopei Zhu, Peiguo Wang, Kunyu Yang, Yan Sun, Weidong Li, Zhendong Li, Cuihong Jiang, Qingqing Cai, Meiyu Fang, Man Hu, Minghua Ge, Wei Zhou, Sichen Li, Ye Guo","doi":"10.1007/s11523-026-01243-y","DOIUrl":"10.1007/s11523-026-01243-y","url":null,"abstract":"<p><strong>Background: </strong>FGF/FGFR alterations are recurrent but heterogeneous in head and neck cancer, and which types predict benefit from selective fibroblast growth factor receptor (FGFR) inhibition is unknown.</p><p><strong>Objective: </strong>We examined whether response to gunagratinib, a pan-FGFR1-4 inhibitor, differs by FGF/FGFR alteration type in recurrent or metastatic head and neck cancer.</p><p><strong>Methods: </strong>Patients with recurrent or metastatic head and neck cancer and fibroblast growth factor(FGF)/FGFR alterations treated with gunagratinib in two prospective trials were combined (phase I ICP-CL-00301, n = 10; phase IIa ICP-CL-00304 at the recommended phase II dose [RP2D] of 20 mg once daily, n = 27). Confirmed objective response rate (Response Evaluation Criteria in Solid Tumours [RECIST] Version 1.1, investigator assessed) was the primary endpoint. Exploratory analyses examined efficacy by alteration type, with an RP2D sensitivity analysis and post-hoc CCND1 outcomes.</p><p><strong>Results: </strong>Among 37 patients (23 head and neck squamous cell carcinoma, 9 nasopharyngeal carcinoma, 5 other; 78.4% with three or more prior therapy lines), confirmed the objective response rate at the RP2D (n = 27) was 7.4% (95% confidence interval 0.9-24.3) and disease control rate 55.6%, with no responses among FGFR-mutant patients (0/6) and single responses among fusions (1/2) and amplifications (1/6). In the pooled cohort (N = 37, including ten treated at sub-RP2D doses), objective response rate was 13.5% (95% confidence interval 4.5-28.8), disease control rate 56.8%, median progression-free survival 4.1 months, median duration of response 11.0 months and median overall survival 7.4 months. Four of five responses arose in receptor-level FGFR alterations rather than FGF3/4/19 amplification alone; because both mutation responses occurred at sub-RP2D doses, this pattern is hypothesis generating. Grade ≥3 treatment-related adverse events occurred in 35.1%, most commonly hyperphosphataemia; no treatment-related deaths occurred.</p><p><strong>Conclusions: </strong>At the RP2D, gunagratinib monotherapy had limited activity (0/6 among FGFR-mutant tumours). In the pooled cohort, confirmed responses concentrated among FGFR receptor-level alterations rather than the FGF3/4/19-amplified majority; because part of this signal came from sub-RP2D dosing, alteration type is a candidate enrichment criterion requiring prospective RP2D testing.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, NCT03758664 (registered 29 November, 2018) and NCT05372120 (registered 12 May, 2022, retrospectively).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"735-748"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World 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}