Targeted Oncology最新文献

{"title":"Role of immunotherapy in early breast cancer: past, present, and future.","authors":"Karissa Britten, Aditya Bardia, Nicholas McAndrew","doi":"10.1007/s11523-025-01157-1","DOIUrl":"10.1007/s11523-025-01157-1","url":null,"abstract":"<p><p>The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment over the last decade, starting with the US Food and Drug Administration (FDA) approval of ipilimumab in 2011. Since that time, the FDA has approved nine additional ICIs, which now serve as frontline agents in lung, colorectal, head and neck, genitourinary, and skin cancers. ICIs have been practice-changing across many cancer subtypes, and their role in breast cancer (particularly in early-stage disease) is a topic of ongoing research. The only current FDA-approved ICI indication in early breast cancer is for the use of pembrolizumab in high-risk, triple-negative breast cancer in combination with chemotherapy, based on results from the KEYNOTE-522 trial. Although numerous trials have further investigated the use of ICIs in early-stage triple-negative breast cancer, survival outcomes have been inconsistent. Studies investigating the use of ICIs in early-stage estrogen receptor-positive and human epidermal growth factor receptor 2-positive breast cancer are even more limited, although available data (especially for estrogen receptor-positive disease) are promising. Numerous studies are ongoing, including critical investigations into biomarkers that may help determine which patients with breast cancer are most likely to benefit from the addition of immunotherapy. In this review, we discuss the history of ICI development, key trials investigating the use of ICIs in early-stage breast cancer, and future directions in the field.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333908","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":"Streamlining and Accelerating the Molecular Tumor Board Process at the University Medical Center Hamburg-Eppendorf.","authors":"Layla Tabea Riemann, Maximilian Ataian, Felicia P S Hähner, Benjamin Roth, Alexander Knurr, Anne Kamitz, Maximilian Christopeit, Carsten Bokemeyer, Frank Ückert","doi":"10.1007/s11523-025-01160-6","DOIUrl":"https://doi.org/10.1007/s11523-025-01160-6","url":null,"abstract":"<p><strong>Background: </strong>We developed, introduced, and evaluated Molecular ONcology Optimized CLinical Evaluation (MONOCLE), a secure, open-source web application at the University Medical Center Hamburg-Eppendorf (UKE), to optimize the analysis and discussion of complex cancer cases in molecular tumor boards (MTB).</p><p><strong>Objective: </strong>MONOCLE standardizes and harmonizes documentation, while its integrated Knowledge Connector accelerates literature research for personalized treatment.</p><p><strong>Patients and methods: </strong>The system was designed by merging the requirements of the German Network for Personalized Medicine (DNPM), the medical staff involved in the MTB process, and the team developing MONOCLE. The usability was evaluated using the System Usability Scale (SUS) and user tasks. Overall process optimization was measured by the number of automated tasks that can be performed.</p><p><strong>Results: </strong>MONOCLE, introduced into clinical practice in June 2024, significantly reduces time for documentation, as three manual steps now run automatically, and transfer of the data to the DNPM is possible. Its usability and SUS showed positive results, ranging between 92.5 and 97.5.</p><p><strong>Conclusions: </strong>As the first open-source and extendable solution for standardized MTB documentation, MONOCLE enables wider adoption by other medical centers.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317895","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":"A Bayesian Network Meta-analysis of Systemic Treatments for Metastatic Castration-Resistant Prostate Cancer in First- and Subsequent Lines.","authors":"Marie Wosny, Stefanie Aeppli, Stefanie Fischer, Tobias Peres, Christian Rothermundt, Janna Hastings","doi":"10.1007/s11523-025-01148-2","DOIUrl":"https://doi.org/10.1007/s11523-025-01148-2","url":null,"abstract":"<p><strong>Background: </strong>Metastatic castration-resistant prostate cancer (mCRPC) presents a challenge for clinicians in determining the optimal treatment sequence because of the lack of direct head-to-head comparisons, which is further complicated by the now-widespread use of androgen receptor pathway inhibitors (ARPIs) in metastatic hormone-sensitive prostate cancer (mHSPC).</p><p><strong>Objective: </strong>This study is a Bayesian network meta-analysis (NMA) intended to provide a comprehensive evaluation and comparison of the efficacy of mCRPC treatments across different treatment lines.</p><p><strong>Patients and methods: </strong>We performed a systematic search of ClinicalTrials.gov, extracted information, assessed the risk of bias, and reconstructed missing outcomes. We performed an NMA to evaluate treatment efficacy for overall survival (OS) and progression-free survival (PFS) in first and subsequent lines. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) NMA guidelines and was registered with PROSPERO (CRD42024499607).</p><p><strong>Results: </strong>The NMA included 43 trials with 33,494 patients. ARPI-based therapies, particularly in combination with poly(ADP-ribose) polymerase inhibitors, demonstrated the most significant benefits for OS and PFS in first-line mCRPC treatment, followed by chemotherapy regimens. However, ARPI re-treatment showed limited effectiveness in subsequent lines, leading to weaker OS and PFS benefits.</p><p><strong>Conclusions: </strong>This NMA highlights the superiority of ARPI-based therapies and chemotherapies as first-line options for mCRPC while emphasizing the need for treatment class switching after ARPI failure. To refine treatment sequencing and enable precision care, future research should integrate individual participant data to better address patient-level heterogeneity and identify biomarkers for personalized therapy.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258999","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":"Circulating Tumor DNA in Advanced EGFRex20+ NSCLC: Concordance with Tissue Biopsy, Monitoring of Response, and Resistance to High-Dose Osimertinib.","authors":"Fenneke Zwierenga, M Benthe Muntinghe-Wagenaar, Pim Rozendal, Adrianus J de Langen, Lizza E L Hendriks, Michel van den Heuvel, Cor van der Leest, Sayed M S Hashemi, Paul van der Leest, T Jeroen N Hiltermann, Ed Schuuring, Anthonie J van der Wekken","doi":"10.1007/s11523-025-01153-5","DOIUrl":"https://doi.org/10.1007/s11523-025-01153-5","url":null,"abstract":"<p><strong>Background: </strong>High-dose osimertinib shows modest anti-tumor activity and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor exon 20 mutation (EGFRex20+). Plasma-derived circulating tumor DNA (ctDNA) is promising in monitoring responses and detecting resistance mechanisms to therapy.</p><p><strong>Objective: </strong>We aimed to assess the concordance between variants detected in ctDNA to those found in corresponding tissue samples at baseline and progression, to analyze alterations in mutant ctDNA levels of EGFRex20+ variants as predictors of therapy response, and to identify resistance mechanisms to high-dose osimertinib as well as examine changes in mutant ctDNA levels of EGFRex20+ variants.</p><p><strong>Patients and methods: </strong>Twenty-five patients with EGFRex20+ NSCLC received double dose (160 mg) osimertinib daily. Blood plasma was collected at baseline, 6 weeks after therapy start (T6), and at progression. ctDNA analysis was performed using the NGS Guardant360 CDx panel. The molecular profile at progression was compared with baseline/T6, and changes in ctDNA levels of the EGFRex20+ variants were linked to response or resistance.</p><p><strong>Results: </strong>Collected ctDNA samples were analyzed retrospectively. Baseline ctDNA showed somatic alterations in 19/20 patients (95%) and the corresponding tumor biopsy NGS EGFRex20+ variant in 65%. Among 14 patients with profiling at all timepoints, there was no significant correlation between changes in mutant ctDNA levels and osimertinib response. At T6, nine patients showed decreased EGFRex20+ levels, with eight also showing tumor shrinkage. At disease progression, 9/14 (64%) patients had increased EGFRex20+ levels, correlating with tumor growth. Variants potentially associated with resistance were found in 11/18 patients (61%): single nucleotide variants (SNV, n = 14), insertions (n = 2), and gene fusions (n = 1). Mutations previously related to osimertinib resistance were found, including EGFR p.C797S (n = 1).</p><p><strong>Conclusions: </strong>ctDNA analysis tracks variant dynamics and can identify resistance mechanisms in patients with EGFRex20+ NSCLC treated with high-dose osimertinib, offering valuable new insights.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235312","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":"A Phase I Study of the Anti-CEACAM6 Antibody Tinurilimab (BAY 1834942) in Patients with Advanced Solid Tumors.","authors":"Lillian L Siu, David S Hong, Wolf-Dietrich Döcke, Reimo Tetzner, Mark Trautwein, Charles Phelps, Joerg Willuda, Xiang Qing Yu, Hendrik Nogai, Melissa Johnson, Boon Cher Goh","doi":"10.1007/s11523-025-01154-4","DOIUrl":"https://doi.org/10.1007/s11523-025-01154-4","url":null,"abstract":"<p><strong>Background: </strong>Tinurilimab is a humanized immunoglobulin G subclass 2 antibody that blocks carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), an immune checkpoint regulator that is overexpressed in several tumor types.</p><p><strong>Objectives: </strong>This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and tumor response profile of tinurilimab in patients with advanced solid tumors with a described expression of CEACAM6.</p><p><strong>Patients and methods: </strong>In this first-in-human, dose-escalation and dose-expansion study, tinurilimab was administered as a 1-h intravenous infusion in 21-day cycles at a starting dose of 2.5 mg, with a planned escalation up to 1800 mg. Following observation of treatment toxicity (cytokine release syndrome in one patient and neutropenia in all patients treated at 30 mg), a premedication regimen was initiated that included dexamethasone 8 mg before and after dosing. Thirty patients received treatment across six dosing cohorts (2.5-100 mg with or without dexamethasone).</p><p><strong>Results: </strong>The maximum tolerated dose was not determined, as the study was terminated due to an unfavorable benefit/risk assessment. All 30 patients (100%) treated with tinurilimab experienced at least one treatment-emergent adverse event of any grade, most commonly fatigue (36.7%), infusion-related reaction (30.0%), and neutropenia (26.7%). The most common grade ≥ 3 treatment-related adverse events were neutropenia (23.3%), followed by febrile neutropenia, cytokine release syndrome, increased hepatic enzymes, decreased lymphocyte count, hypophosphatemia, lactic acidosis, and acute kidney injury (3.3% each). No patients reported an objective response.</p><p><strong>Conclusions: </strong>Following study termination, the clinical development program for tinurilimab was discontinued permanently.</p><p><strong>Clinical trial registration: </strong>www.</p><p><strong>Clinicaltrials: </strong>gov , NCT03596372.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216928","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":"Efficacy and Safety of Anti-GD2 Immunotherapy with Dinutuximab Beta in the Treatment of Relapsed/Refractory High-Risk Neuroblastoma.","authors":"Aleksandra Wieczorek, Katarzyna Śladowska, Holger N Lode","doi":"10.1007/s11523-025-01155-3","DOIUrl":"https://doi.org/10.1007/s11523-025-01155-3","url":null,"abstract":"<p><strong>Background: </strong>High-risk neuroblastoma (HR-NB) is associated with a poor prognosis. Standard first-line maintenance therapy with anti-disialoganglioside 2 (GD2) monoclonal antibodies, such as dinutuximab beta, has improved survival rates; however, approximately 50% of patients experience relapse and ~15% have disease that is refractory to induction therapy.</p><p><strong>Objective: </strong>This systematic literature review aimed to evaluate response rates, survival outcomes, and safety in patients with relapsed or refractory (R/R) HR-NB receiving dinutuximab beta as maintenance therapy.</p><p><strong>Patients and methods: </strong>We searched the PubMed, Embase, and Cochrane Library databases and regulatory reports from inception to 1 September 2024, and included studies of patients with R/R HR-NB in which dinutuximab beta (± isotretinoin) was used as maintenance therapy and that reported objective response or survival rates. Studies of dinutuximab beta plus chemotherapy combinations were excluded.</p><p><strong>Results: </strong>We included nine publications/reports representing seven studies and 442 patients receiving dinutuximab beta. Across studies, the mean age was 5.1-6.4 years, and most patients were male. Reporting of response varied across studies between best response and end-of-treatment response. Best response rates with dinutuximab beta were 28.6-54.8%. All studies reported overall survival (OS), but follow-up times varied. Where reported, 3-year OS rates for patients receiving dinutuximab beta were 54-86% overall, with better OS rates reported for refractory than relapsed patients. Adverse events were frequent but manageable.</p><p><strong>Conclusions: </strong>Maintenance therapy for patients with R/R HR-NB with dinutuximab beta as monotherapy or in combination with isotretinoin demonstrated efficacy and acceptable safety. Further studies are needed in patients previously treated with anti-GD2 therapies to evaluate efficacy and impact on target antigens.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209585","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":"PSMA PET Imaging in the Management of Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Radioligand Therapy.","authors":"Phillip H Kuo, Jeremie Calais, Mike Crosby","doi":"10.1007/s11523-025-01151-7","DOIUrl":"https://doi.org/10.1007/s11523-025-01151-7","url":null,"abstract":"<p><p>Despite an evolving treatment landscape for people with metastatic castration-resistant prostate cancer, prognosis for this patient population remains poor. Prostate-specific membrane antigen positron emission tomography (PSMA PET) imaging may be used to identify patients with PSMA-positive (and no significant PSMA-negative) metastatic castration-resistant prostate cancer who could benefit from PSMA-targeted radioligand therapy. As the PSMA PET imaging and treatment landscape expands, there is a growing need for guidance and greater utilization of PSMA-targeted tracers and radioligand therapies to improve outcomes for patients with metastatic castration-resistant prostate cancer. This review discusses the current clinical considerations of PSMA PET, including the various imaging agents available and how best to identify patients eligible for PSMA PET imaging and subsequent PSMA-targeted radioligand therapy. This review also examines opportunities to mitigate discordant findings, as well as considerations around the standardization of reporting of PSMA PET imaging, key gaps in the evidence base, and guidance around the use of PSMA PET in clinical and research settings.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143611","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":"Relugolix in Combination with Androgen Receptor Pathway Inhibitors in the Treatment of Metastatic Prostate Cancer: A Clinical Perspective.","authors":"Tomas Buchler","doi":"10.1007/s11523-025-01150-8","DOIUrl":"https://doi.org/10.1007/s11523-025-01150-8","url":null,"abstract":"<p><p>Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, has been established as an effective androgen deprivation therapy (ADT) for advanced prostate cancer, offering advantages over traditional GnRH agonists. The combination of relugolix with androgen receptor pathway inhibitors (ARPIs) is increasingly utilized in clinical practice, necessitating an understanding of its pharmacokinetics, efficacy, safety, and drug-drug interactions. This review explores the real-world data and clinical studies evaluating relugolix coadministration with ARPIs, including enzalutamide, abiraterone, apalutamide, and darolutamide. Pharmacokinetic interactions, particularly via the CYP3A4 enzyme system and P-glycoprotein (P-gp) transporter, influence drug exposure and, in theory, necessitate dose adjustments in certain combinations. However, clinical studies and real-world studies suggest that relugolix maintains testosterone suppression when combined with ARPIs even if administered in a standard dose. While these findings support the efficacy and safety of relugolix-based combination therapy, further large-scale prospective trials are needed to refine treatment recommendations and provide information on long-term outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080474","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":"Teclistamab Dosing in Responders: Modeling and Simulation Results from the MajesTEC-1 Study in Relapsed/Refractory Multiple Myeloma.","authors":"Yue Guo, Jin Niu, Natalia A Quijano Cardé, Liviawati Wu, Xin Miao, Shalla Hanson, Yaming Su, Carlos Pérez Ruixo, Deeksha Vishwamitra, Katherine Chastain, Mahesh N Samtani, Weirong Wang, Nahor Haddish-Berhane","doi":"10.1007/s11523-025-01149-1","DOIUrl":"https://doi.org/10.1007/s11523-025-01149-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Based on the phase I/II MajesTEC-1 study, the B-cell maturation antigen (BCMA) and cluster of differentiation (CD)3 bispecific antibody, teclistamab, is approved for relapsed/refractory multiple myeloma (RRMM) at a dose of 1.5 mg/kg weekly (QW), with the option to switch to 1.5 mg/kg every other week (Q2W) in patients maintaining complete response (CR) or better for ≥ 6 months on the QW schedule.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;We report the pharmacokinetics (PK), pharmacodynamics, and anticancer activity of teclistamab 1.5 mg/kg Q2W, and the PK of teclistamab 3 mg/kg every 4 weeks (Q4W), on the basis of modeling and simulation results from MajesTEC-1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Teclistamab PK was assessed using a population PK approach. Exposure-response analysis was based on individual estimated teclistamab serum trough concentration (C&lt;sub&gt;trough&lt;/sub&gt;). The impact of responders switching to Q2W teclistamab dosing on the formation of the key pharmacological species that drive the mechanism of action of teclistamab (i.e., the trimer formed by simultaneous engagement of teclistamab with BCMA on target multiple myeloma cells and CD3 on effector T cells) was estimated using a quantitative systems pharmacology (QSP) model. Additionally, steady-state teclistamab PK and trimer was simulated for the 1.5 mg/kg Q2W and Q4W (3 mg/kg or 1.5 mg/kg) doses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Median estimated teclistamab serum C&lt;sub&gt;trough&lt;/sub&gt; was lower after the first and fourth Q2W doses (14.4 and 11.7 µg/mL, respectively) than after QW doses (20.4 µg/mL) but remained above the 90% maximal effective concentration. No statistically significant exposure-response trend was observed for duration of response (DOR), progression-free survival, or overall survival in responders who switched to teclistamab 1.5 mg/kg Q2W dosing. Despite the lower teclistamab serum C&lt;sub&gt;trough&lt;/sub&gt;, the QSP model estimated comparable target cell-biologics-effector cell (TBE) trimer formation, tumor volume reduction, and DOR for responders switching to 1.5 mg/kg Q2W dosing versus not switching. Steady-state exposure metrics and trimer formation with teclistamab 3 mg/kg Q4W were estimated to be comparable with those at 1.5 mg/kg Q2W.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;MajesTEC-1 modeling and simulation results, which contributed to the teclistamab label update, support the approved switch to teclistamab 1.5 mg/kg Q2W in patients maintaining ≥ CR for ≥ 6 months on the QW dose, without negatively impacting clinical efficacy. In addition, it is estimated that the 3 mg/kg Q4W schedule will provide maintenance of response comparable with the 1.5 mg/kg Q2W schedule. Teclistamab 3 mg/kg Q4W dosing will be evaluated in &gt; 800 patients in three phase III studies in early line RRMM (MajesTEC-3, MajesTEC-9, and MonumenTAL-6) and in 100 patients in RRMM in the phase I MajesTEC-10 study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical trial registration: &lt;/strong&gt;NCT03145181 (phase I,","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014706","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":"Safety and Tolerability of Relugolix in Combination with Abiraterone or Apalutamide for Treatment of Patients with Advanced Prostate Cancer: Data from a 52-Week Clinical Trial.","authors":"Jose De La Cerda, Laurence Belkoff, Kevin D Courtney, Elan Diamond, James D'Olimpio, Curtis Dunshee, Lawrence Gervasi, Michael Goodman, Kriti Mittal, David Morris, Paul Sieber, Ronald Tutrone, Michael Ryan, Yi Zhong, Mike Ufer, Neal Shore","doi":"10.1007/s11523-025-01139-3","DOIUrl":"10.1007/s11523-025-01139-3","url":null,"abstract":"<p><strong>Background: </strong>The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix is the only oral androgen deprivation therapy (ADT) indicated for advanced prostate cancer (aPC). Combining ADT with androgen receptor signaling inhibitors (ARSIs) has shown improved clinical outcomes.</p><p><strong>Objective: </strong>To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of relugolix in combination with ARSIs in patients with aPC.</p><p><strong>Methods: </strong>In this 52-week, open-label study, patients received relugolix (120 mg once daily) with abiraterone (1,000 mg once daily) and corticosteroid (Part 1) or relugolix (240 mg once daily) with apalutamide (240 mg once daily) (Part 2). Metastatic castration-sensitive patients were eligible for both parts, whereas castration-resistant patients were eligible for Part 1 if metastatic and Part 2 if non-metastatic. Adverse events and other safety data were evaluated over 52 weeks, while pharmacodynamic and pharmacokinetic (Part 2 only) data were assessed over 12 weeks. Medication adherence to relugolix was measured by pill count.</p><p><strong>Results: </strong>Of 48 patients, 21 completed Part 1 and 20 completed Part 2. Most adverse events were grade 1 or 2, with hypertension (Part 1) and rash (Part 2) being most common. Mean testosterone concentrations remained below castrate level. Median prostate-specific antigen concentration was 0.04 ng/mL at week 12 in both parts. Concentrations of relugolix, apalutamide, and N-desmethyl-apalutamide were stable over 12 weeks similar to previous data. Relugolix adherence rates were > 97% in both parts.</p><p><strong>Conclusions: </strong>The safety/tolerability profile of both combination therapies was consistent with those of the individual drugs. These findings support using relugolix in combination with abiraterone or apalutamide as treatment of aPC.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT04666129.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"503-517"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781165","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}