Targeted Oncology最新文献

{"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}

{"title":"PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor Degraders for Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.","authors":"Erika P Hamilton, Rinath M Jeselsohn, Linda T Vahdat, Sara A Hurvitz","doi":"10.1007/s11523-025-01137-5","DOIUrl":"10.1007/s11523-025-01137-5","url":null,"abstract":"<p><p>The estrogen receptor (ER) signaling pathway is a key driver of breast cancer, primarily through the activation of genes that promote tumor cell survival and growth. The recommended first-line treatment for ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer is endocrine therapy plus a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. However, most patients experience disease progression, and there is no clear standard of care in the second-line setting. Thus, novel treatments in the advanced setting are needed. In this narrative review, we describe the unique mechanisms of action of a new class of drugs called PROteolysis TArgeting Chimera (PROTAC) ER degraders. Unlike other ER-targeted therapies, these small molecules harness the body's primary intracellular natural protein disposal machinery, the ubiquitin-proteasome system, to directly induce ER degradation. Vepdegestrant (ARV-471) is the furthest advanced PROTAC ER degrader currently in clinical development. Preclinical data demonstrate increased tumor growth inhibition with vepdegestrant alone or in combination with CDK4/6 inhibitors compared with the selective ER degrader fulvestrant. In a first-in-human phase 1/2 clinical study, vepdegestrant administered orally as monotherapy or in combination with palbociclib showed promising clinical activity and a favorable safety profile in patients with heavily pretreated ER+/HER2- advanced breast cancer. Several other PROTAC ER degraders (AC699, ERD-3111, ERD-4001, and HP568) are in early development and have demonstrated activity in preclinical breast cancer models, with some recently entering clinical trials. The data highlight the potential for PROTAC ER degraders to be a new backbone therapy in breast cancer.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"431-444"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039225","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":"Olaparib Monotherapy or in Combination with Abiraterone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) and a BRCA Mutation.","authors":"Fred Saad, Andrew J Armstrong, Neal Shore, Daniel J George, Mototsugu Oya, Mikio Sugimoto, Rana R McKay, Maha Hussain, Noel W Clarke","doi":"10.1007/s11523-025-01146-4","DOIUrl":"10.1007/s11523-025-01146-4","url":null,"abstract":"<p><p>Treatment strategies to improve outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) are evolving. Of particular interest are therapies that target DNA damage responses in tumor cells by inhibiting poly(ADP-ribose) polymerase (PARP) activity. Several PARP inhibitors have recently received regulatory approval for the treatment of patients with mCRPC, of which olaparib was the first for prostate cancer. Olaparib received approval as a monotherapy following the PROfound study (NCT02987543) and in combination with abiraterone following the PROpel study (NCT03732820) for mCRPC. Both PROfound (homologous recombination repair mutation biomarker-selected) and PROpel (biomarker unselected) patients demonstrated statistically significant longer radiographic progression-free survival (rPFS) with olaparib versus their respective control arms in the intention-to-treat population. In both studies, the greatest clinical benefit with olaparib was seen in patients with BRCA1 and/or BRCA2 mutations (BRCAm): PROfound rPFS hazard ratio (HR) 0.22 (95% confidence interval [CI] 0.15-0.32); PROpel rPFS HR 0.23 (95% CI 0.12-0.43). Clinical benefit was also observed in terms of overall survival: PROfound HR 0.63 (95% CI 0.42-0.95); PROpel HR 0.29 (95% CI 0.14-0.56). We provide a comprehensive overview of the utility of olaparib for patients with mCRPC harboring a BRCAm. Key clinical and safety data in BRCAm subgroup populations are discussed, predominantly based on findings from PROfound and PROpel, as well as investigator-initiated studies, to help inform treatment decision-making in this patient population. We also discuss the importance of genetic testing to identify patients who may optimally benefit from treatment with olaparib, either as a monotherapy or in combination with abiraterone.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"445-466"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111956","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":"Navigating the Landscape of Resistance Mechanisms in Antibody-Drug Conjugates for Cancer Treatment.","authors":"Gloria Lalli, Ilaria Sabatucci, Mariachiara Paderno, Fabio Martinelli, Mauro Signorelli, Matteo Maruccio, Giampaolo Di Martino, Giovanni Fucà, Domenica Lorusso","doi":"10.1007/s11523-025-01140-w","DOIUrl":"10.1007/s11523-025-01140-w","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are an innovative approach in cancer therapy, combining the specificity of monoclonal antibodies (mAb) with the cytotoxic effect of chemotherapy agents. Despite the remarkable efficacy demonstrated in clinical studies, primary and secondary resistance to ADCs represent a concern and a significant challenge. Known resistance mechanisms mainly involve the targeted tumor antigen; the internalization, trafficking, and cleavage processes; the cytotoxic payload; and the intrinsic tumor cell dynamics of cell death and cell signaling. Key strategies to overcome these resistance mechanisms include the use of antibodies targeting the same antigen but with different payloads, developing dual-payload ADCs that target multiple cellular pathways, switching from non-cleavable to cleavable linkers, and combining ADCs with other therapies such as immune checkpoint inhibitors and antiangiogenic agents. By improving our understanding of what underlies the mechanisms of resistance to ADCs and implementing and studying systems to overcome these mechanisms, as well as using innovative therapeutic combinations, ADCs have the potential to continue to play a fundamental role in the treatment of tumors, especially refractory ones, providing patients with more effective and long-lasting therapeutic options, as well as better outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"419-430"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018789","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 of First-Line Treatments for Advanced Renal Cell Carcinoma: A Bayesian Network Meta-analysis of Objective Response, Progression-Free Survival, and Overall Survival.","authors":"Manuela Schmidinger, Pratik P Rane, Kevin Yan, Eric Druyts, Joseph Burgents, Murali Sundaram, Avivit Peer","doi":"10.1007/s11523-025-01147-3","DOIUrl":"10.1007/s11523-025-01147-3","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study was to indirectly compare pembrolizumab + lenvatinib to other treatments of interest for first-line advanced renal cell carcinoma (aRCC).</p><p><strong>Methods: </strong>A systematic literature review searched EMBASE, MEDLINE, and CENTRAL databases for relevant randomized controlled trials of interest up to 30 January 2024, with an updated search conducted on 17 March 2025. A fixed effect Bayesian network meta-analysis (NMA) was conducted to determine the relative treatment effects for overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).</p><p><strong>Results: </strong>When comparing against other immune checkpoint inhibitors (ICI), a statistically significant improvement in PFS was demonstrated between pembrolizumab + lenvatinib compared with nivolumab + ipilimumab (hazard ratio (HR) = 0.53; 95% credible interval (CrI): 0.40-0.71), avelumab + axitinib (HR = 0.71; 95% Crl: 0.53-0.94), atezolizumab + bevacizumab (HR = 0.54; 95% CrI: 0.40-0.73), and pembrolizumab + axitinib (HR = 0.69; 95% CrI: 0.51-0.91). Treatment with pembrolizumab + lenvatinib resulted in no statistically significant difference between pembrolizumab + lenvatinib and other combination ICI-based therapies for OS. A statistically significant higher ORR was shown for pembrolizumab + lenvatinib compared with nivolumab + ipilimumab (odd ratio (OR) = 3.29; 95% Crl: 2.21-4.93), pembrolizumab + axitinib (OR = 1.92; 95% CrI: 1.27-2.94), atezolizumab + bevacizumab (OR = 4.05; 95% Crl: 2.71-6.05), bempegaldesleukin + nivolumab (OR = 6.20; 95% CrI: 3.69-10.48), and nivolumab (OR = 5.92; 95% CrI: 2.70-13.24).</p><p><strong>Conclusions: </strong>The overall population analysis indicated that pembrolizumab + lenvatinib improves PFS and ORR compared with other approved ICI combination therapies in first-line aRCC. No significant differences in OS were observed between pembrolizumab + lenvatinib and other combination immune checkpoint inhibitor-based therapies.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"375-387"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000290","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":"CIBMTR Registry Data on Inotuzumab Ozogamicin Treatment in Patients with ALL Who Proceeded to Hematopoietic Stem Cell Transplant-A Podcast.","authors":"Marcos de Lima, David I Marks","doi":"10.1007/s11523-025-01129-5","DOIUrl":"10.1007/s11523-025-01129-5","url":null,"abstract":"<p><p>Inotuzumab ozogamicin (InO) was approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) on the basis of the phase 3 INO-VATE trial, which found that treatment-related mortality (TRM), primarily due to hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), was higher among patients who received InO versus standard therapy and proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). Here, we use real-world data obtained from the Center for International Blood and Marrow Transplant Research database to evaluate post-HSCT outcomes in adult patients with ALL who received InO from 18 August2017 to 18 August 2022. Post-HSCT follow-up data were available for 244 patients with ALL (including 156 with R/R ALL) who received InO. VOD incidence within 100 days of HSCT was 14% among all patients and 18% among patients with R/R ALL. These data are consistent with a pooled analysis of the phase 1/2 study 1010 and the phase 3 INO-VATE trial that reported VOD in 19% of patients who received InO and proceeded to HSCT (n = 101). The current study demonstrates VOD incidence among patients receiving InO prior to HSCT in the real world is similar to that reported in clinical trials. Supplementary file1 (MP4 165809 KB).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"371-374"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671101","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 Toxicity of Pemigatinib in Advanced Cholangiocarcinoma Harboring FGFR Fusions or Rearrangements: A Systematic Review and Meta-analysis.","authors":"Erman Akkus, Hatime Arzu Yasar, Lorenza Rimassa, Angela Lamarca","doi":"10.1007/s11523-025-01142-8","DOIUrl":"10.1007/s11523-025-01142-8","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of pemigatinib in advanced cholangiocarcinoma (aCCA) were presented in phase I-II trials and retrospective reports, with small sample sizes and variable results.</p><p><strong>Methods: </strong>A systematic literature search included studies investigating the efficacy/safety of pemigatinib in aCCA harboring FGFR fusions/rearrangements. Primary outcomes were objective response rate (ORR) and treatment-related adverse events (AEs). A pooled proportion meta-analysis was performed.</p><p><strong>Results: </strong>Three hundred and twenty-seven patients in eight studies were included (three phase-II, one phase-I/II, two phase-I, and two retrospective). In the pooled analyses, the median age was 58.9 years (95% confidence interval (CI): 51.9-65.8); 33.4% (95% CI: 28.1-39.0) were male. Pemigatinib was the second-line treatment in 58.5% (95% CI: 52.7-64.1) and was beyond second-line in the remaining. ORR was 42.2% (95% CI: 35.9-48.7) (I²:48.4%) and disease control rate (DCR) was 86.5% (95% CI: 81.6-90.5) (I²: 58.8%). Median progression-free survival (PFS) was 7.8 months (95% CI: 6.2-9.4) (I²: 11.6%). Two studies reported overall survival (OS) (median 17.5 and 17.1 months). The most common AEs (any grade) were hyperphosphatemia (46%), dysgeusia (33.2%), alopecia (31.4%), fatigue (30.9%), stomatitis (28.5%), and diarrhea (27.5%). Cumulative eye and nail toxicities were observed in 32.5% and 40.9%, and retinal detachment in 5.5%.</p><p><strong>Conclusion: </strong>This analysis emphasizes the FGFR alteration testing and pemigatinib use in the second-line and beyond treatment of aCCA.</p><p><strong>Registration id (prospero): </strong>CRD42024627459.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"389-403"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019709","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}