Oncologist最新文献

{"title":"Reference frame for Adult Brainstem gliomas.","authors":"Florence Laigle-Donadey, Emmanuel Mesny, Franck Bielle, Aurélie Kas, Lucia Nichelli, Carole Ramirez, Laura Rozenblum, Olivier Langlois, Guido Ahle, Luc Bauchet, Loic Feuvret, Maxime Fontanilles, Julien Savatovsky, Jean-Marc Constans, Nadya Pyatigorskaya, Mehdi Touat, Julian Jacob, Emmanuel Jouglar, Luc Ollivier, Elsa Magro, Matthieu Boone, Apolline Monfilliette, Enora Vauleon, Philippe Menei, Ahmed Idbaih, Jean-Sébastien Guillamo, Elodie Vauleon, François Ducray, Caroline Dehais, Sylvie Grand, Bertrand Mathon","doi":"10.1093/oncolo/oyag403","DOIUrl":"https://doi.org/10.1093/oncolo/oyag403","url":null,"abstract":"<p><p>Brainstem gliomas (BSG) are rare in adults (less than 2% of all gliomas) and generally have a better prognosis than pediatric BSG, although outcomes remain heterogeneous. Many other central nervous system (CNS) tumors, as well as nontumoral lesions, have been described as differential diagnoses and should be kept in mind. Each case should be examined by neurosurgeons from specialized centers to determine the most appropriate surgical approach among stereotactic biopsy, open biopsy, and tumor resection. Surgery may sometimes be performed in expert centers. The main objectives of tumor tissue sampling are to perform histomolecular analyses to confirm the diagnosis, determine the tumor subtype, and identify potential prognostic and theranostic biomarkers. Tissue preservation is essential to ensure that sufficient tumor material is available for further molecular analyses for diagnostic or therapeutic purposes. Results of ctDNA detection in CSF should only be considered if they are positive. The management of BSGs in adults remains non-standardized, largely because most glioma trials exclude tumors located in this specific site. To date, no prospective trials have established clear treatment guidelines, and most of the available data come from retrospective studies or extrapolation of data from other locations. Radiotherapy (RT) is one of the main treatment options for BSGs in adults. The role of chemotherapy remains unclear due to limited data in literature and is currently being studied. Several molecular targets with therapeutic potential, including recurrent genetic mutations and fusion transcripts, have been identified in adult BSGs.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 2 study of tipifarnib in children and young adults with tumors harboring HRAS genomic alterations: NCI-COG Pediatric MATCH trial (APEC1621M).","authors":"Christine A Pratilas, Marielle E Yohe, P Mickey Williams, Joel M Reid, Jin Piao, Lauren Saguilig, David R Patton, Brent Coffey, Todd A Alonzo, Alexandria M Thompson, Nicole Arwood, Sinchita Roy-Chowdhuri, Nilsa C Ramirez, Stacey L Berg, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, D William Parsons","doi":"10.1093/oncolo/oyag401","DOIUrl":"10.1093/oncolo/oyag401","url":null,"abstract":"<p><strong>Background: </strong>APEC1621 arm M, a subprotocol of the NCI-COG Pediatric MATCH clinical trial, is a phase 2 study evaluating tipifarnib, a farnesyl transferase inhibitor, in patients with relapsed or refractory solid tumors harboring HRAS mutations at codons G12, G13, Q61, or A146 (NCT04284774).</p><p><strong>Methods: </strong>Patients identified by the MATCH screening protocol and enrolled to the arm M subprotocol received tipifarnib at 350 mg/m2/dose (maximum 600 mg/dose) orally twice daily on an intermittent dosing schedule (days 1 to 7 and 15 to 21, every 28 days) until disease progression or intolerable toxicity. The primary aim was to determine the objective response rate (ORR) and secondary objectives included estimating progression-free survival (PFS) and assessing the tolerability of tipifarnib on the intermittent dosing schedule in children.</p><p><strong>Results: </strong>Seven patients matched to the tipifarnib subprotocol and five patients (71%) enrolled. Two matched patients were ineligible for treatment. Diagnoses for the enrolled patients were rhabdomyosarcoma (n = 4) and angiosarcoma (n = 1). HRAS mutations identified in those tumors included G13R (n = 2) and G12S, G12C, and Q61L (n = 1 each). Treatment was associated with grade 1/2 adverse events (AE) consistent with those expected from prior studies. Grade 3 or higher AEs on treatment were disease progression, dyspnea, and pleural effusion, not related to protocol therapy. One patient had stable disease (SD) at the end of cycle two and remained on protocol therapy for four cycles. There were no objective responses (OR).</p><p><strong>Conclusions: </strong>This U.S. cooperative group study was successful at identifying pediatric patients with tumors that harbored oncogenic mutations in HRAS. The frequency of the mutations identified and patients enrolled was lower than anticipated and the study closed before accrual was complete. The adverse effect profile of tipifarnib in pediatric patients on the intermittent dosing schedule was acceptable. Limited single-agent efficacy of tipifarnib was observed in this biomarker-selected cohort of refractory pediatric tumors.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of and risk factors for immune checkpoint inhibitor-related pneumonitis in thoracic malignancies: a prospective multicenter study.","authors":"Yoshihiro Kitahara, Naoki Inui, Takafumi Koyauchi, Kazuhiro Asada, Koji Nishimoto, Shun Matsuura, Dai Hashimoto, Takashi Matsui, Masato Fujii, Nao Inami, Mitsuru Niwa, Keigo Koda, Hiroyuki Matsuda, Yusuke Kaida, Masaki Ikeda, Masaki Sato, Yasuhiro Ito, Yusuke Inoue, Hideki Yasui, Masato Karayama, Yuzo Suzuki, Hironao Hozumi, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Kumi Ozaki, Shintaro Ichikawa, Satoshi Goshima, Takafumi Suda","doi":"10.1093/oncolo/oyag377","DOIUrl":"10.1093/oncolo/oyag377","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have fundamentally changed cancer treatment, but ICI-related pneumonitis (ICI-P) remains a major clinical concern. Although numerous studies have reported its incidence and risk factors, the retrospective nature of these studies makes accurate assessment difficult in a real-world clinical setting.</p><p><strong>Patients and methods: </strong>This prospective multicenter observational study enrolled patients with advanced or recurrent thoracic malignancies treated with nivolumab, pembrolizumab, or atezolizumab. Thoracic high-resolution computed tomography (HRCT) examinations were performed at the start of ICI therapy and at the onset of ICI-P. The primary endpoint was ICI-P incidence. The secondary endpoints included evaluation of risk factors, with a focus on the lung lesions present at ICI initiation. Fine-Gray analyses with 3 models were used to identify risk factors.</p><p><strong>Results: </strong>Among 614 eligible patients, 78 (12.7%) developed ICI-P. During a median observation period of 14.4 months, 29 patients developed grade ≥3 pneumonitis and 7 patients died owing to ICI-P. In the multivariable Fine-Gray analyses, independent risk factors for ICI-P included heavy smoking history (>50 pack-years; subdistribution hazard ratio [SHR], 1.90; 95% confidence interval [CI], 1.17-3.10), baseline interstitial lung abnormalities (ILAs; SHR, 3.42; 95% CI, 2.05-5.71), use of PD-1 inhibitors (SHR, 2.15; 95% CI, 1.28-3.63), and immunochemotherapy (SHR, 2.16; 95% CI, 1.17-3.98).</p><p><strong>Conclusion: </strong>In this prospective real-world cohort, the incidence of ICI-P was relatively high, and ILAs detected by HRCT, heavy smoking history, and treatment with a PD-1 inhibitor alone or in combination with cytotoxic chemotherapy were identified as independent risk factors.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REVERCE II: a phase II trial of regorafenib followed by anti-EGFR therapy versus reverse sequencing in refractory metastatic colorectal cancer.","authors":"Oluseyi B Abidoye, Fang-Shu Ou, Angela Ulrich, Shaylene McCue, Mohamad B Sonbol, Donald Wender, Kelsey Klute, Zhaohui Jin, Heinz-Josef Lenz, John H Strickler, Tanios Bekaii-Saab, Daniel H Ahn","doi":"10.1093/oncolo/oyag307","DOIUrl":"10.1093/oncolo/oyag307","url":null,"abstract":"<p><strong>Background: </strong>Regorafenib and anti-EGFR monoclonal antibodies are standard therapies for RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC) in the refractory setting, but the optimal sequencing remains unknown. Herein, we report results from REVERCE II, a randomized phase II trial evaluating the efficacy and safety of sequencing these therapies.</p><p><strong>Methods: </strong>Patients with RAS WT mCRC previously treated with fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive (R-E) regorafenib followed by anti-EGFR therapy ± irinotecan or (E-R) anti-EGFR therapy ± irinotecan, followed by regorafenib sequentially. The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) with initial (PFS1) and second treatment (PFS2), sequential treatment PFS (stPFS), objective response rate (ORR), and safety. Exploratory endpoints included serial biomarker analyses. Unfortunately, the trial was closed prematurely due to slow enrollment and lack of funding.</p><p><strong>Results: </strong>Twenty-two patients were enrolled (R-E: n = 12; E-R: n = 10) with sequential treatment initiated in 33% (4/12) and 80% (8/10) of patients in R-E and E-R, respectively. Median OS for R-E and E-R was 21.9 and 13.3 months, respectively (one-sided P = .114). PFS1 was 2.5 (R-E) vs 5.6 months (E-R) (one-sided P = .998), while PFS2 was 3.7 vs 2.0 months (one-sided P = .086). stPFS was similar (9.3 vs 9.6 months; one-sided P = .358). ORR for initial treatment was 0% in R-E and 20% (2/8) in E-R. Sequential treatment ORR was 25% (n = 1/4) in R-E and 0% in E-R. No significant differences were observed adverse effects between arms.</p><p><strong>Conclusion: </strong>While the study was closed prematurely prior to completion, the sequence of regorafenib before to anti-EGFR therapy suggested a possible survival benefit. Further studies may help better determine the optimal treatment sequencing strategy in refractory mCRC.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149118660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world treatment patterns in men with metastatic hormone-sensitive prostate cancer in Europe and Asia between 2020 and 2024.","authors":"Amit D Raval, Sheila Mpima, Vicky Casey, Fil Manuguid, Matthew Korn, Elena Castro","doi":"10.1093/oncolo/oyag369","DOIUrl":"10.1093/oncolo/oyag369","url":null,"abstract":"<p><strong>Introduction: </strong>The therapeutic landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has changed significantly over the last decade with the introduction of combination strategies. However, recent real-world evidence on their use in practice is limited, especially in Europe and Asia.</p><p><strong>Patients and methods: </strong>This cross-sectional study included men with mHSPC receiving first-line therapy in EU4, the UK, Japan, and China between January 1, 2020, and December 31, 2024. The IQVIA Oncology Dynamics database was used to derive patient-level data on physician-reported initial treatment for mHSPC.</p><p><strong>Results: </strong>Of 23 101 men included, 15 275, 4875, and 2951 in EU4, the UK and Asia, received treatment for mHSPC. Use of androgen deprivation therapy (ADT) monotherapy ranged from 29% to 44% in EU4/UK and 50% to 59% in Asia. ADT plus androgen receptor pathway inhibitor (ARPI) was used in 47% of patients in EU4, 54% in the UK, and 35% to 38% in Asia. From 2020 to 2024, ADT monotherapy decreased from 60% to 24% in EU4, 54% to 23% in the UK, and 83% to 39% in Asia, with corresponding increases in ADT plus ARPI use. ADT plus ARPI plus docetaxel use increased throughout the study, becoming more prominent from 2023 in EU4/UK; usage went from 0.1% in 2020 to 10% in 2024. Uptake was slower in Asia. Compared with recurrent mHSPC, a high proportion received combination therapy for de novo mHSPC.</p><p><strong>Discussion: </strong>Findings highlight the adoption of combination strategies with either doublet or docetaxel triplet regimens between 2020 and 2024. One-fourth of patients received ADT monotherapy in 2024.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and transcriptomic correlates of deep prostate-specific antigen response in patients with metastatic androgen pathway modulation-sensitive prostate cancer.","authors":"Rana R McKay, Deepak Kilari, Binyam Yilma, Unnati Jariwala, Arya Ashok, Stamatina Fragkogianni, Jacob Mercer, Neeraj Agarwal, Emmanuel S Antonarakis","doi":"10.1093/oncolo/oyag368","DOIUrl":"10.1093/oncolo/oyag368","url":null,"abstract":"<p><strong>Background: </strong>Despite advances in metastatic androgen pathway modulation-sensitive prostate cancer (mAPMS) treatment, outcomes remain heterogeneous. Achieving a post-treatment undetectable prostate-specific antigen (PSA) is a strong prognostic marker. We aimed to identify genomic and transcriptomic determinants of PSA response in a real-world clinical-genomic cohort.</p><p><strong>Patients and methods: </strong>Patients with mAPMS who underwent DNA (Tempus xT) and, in a subset, RNA (Tempus xR) sequencing were identified from the Tempus Lens database. Inclusion required stage IV disease within 90 days of sample collection and obtained within 12 months before or 3 months after treatment initiation. Patients with PSA at 6 months (n = 525) were classified as PSA-Low (<0.1 ng/mL, n = 240) or PSA-High (≥0.1 ng/mL, n = 285). Overall survival (OS) was assessed by 6-month landmark analysis with delayed-entry adjustment. Logistic and Cox models were adjusted for clinical variables. Sensitivity analyses used a relative definition of >95% PSA decline from baseline.</p><p><strong>Results: </strong>Baseline PSA was lower in PSA-Low versus PSA-High patients (24 vs 36 ng/mL, P = .01). SPOP (17% vs 11%) and ZFHX3 (2.5% vs 6%) alterations differed between groups, but neither persisted after adjustment. Using the relative definition, ZMYM3 and JAK1 alterations were independently associated with failure to achieve a deep PSA response. Expression of PSMA, TROP2, B7-H3, and STEAP1 did not differ between groups. PSA-Low status was independently associated with improved OS, as was deep relative response.</p><p><strong>Conclusion: </strong>Deep PSA response at 6 months correlates with improved OS in mAPMS. Integrating molecular markers with PSA response may inform treatment intensification or de-escalation strategies.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of metastatic solid pseudopapillary neoplasms.","authors":"Courtney Porfido, Diane Reidy-Lagunes, Nitya Raj","doi":"10.1093/oncolo/oyag393","DOIUrl":"10.1093/oncolo/oyag393","url":null,"abstract":"<p><strong>Background: </strong>Surgical resection is the primary treatment for solid pseudopapillary neoplasms (SPN). Systemic treatment options are limited; no prospective trials or consensus guidelines exist given the rarity of SPN.</p><p><strong>Patients and methods: </strong>We retrospectively reviewed patients treated for SPN at Memorial Sloan Kettering Cancer Center from 2009-2024, summarizing demographics, treatments, outcomes, and genetic testing results when available.</p><p><strong>Results: </strong>Of 45 patients, 42 (93%) underwent surgical resection and 8 (18%) received systemic or locoregional treatment (average 3.25 therapies per patient). Genetic testing was available for 10 patients (22%), 9 of whom had Wnt/β-catenin pathway alterations. One patient whose tumor harbored a CTNNB1 mutation was treated with an investigational therapy inhibiting β-catenin, achieving disease control for 7 months.</p><p><strong>Conclusion: </strong>This is the largest single-institution series of treatment of advanced SPN, demonstrating that select therapies can provide disease control. Molecular characterization of SPN frequently identifies Wnt/β-catenin pathway alterations, demonstrating a potential clinical benefit for drugs targeting this pathway.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Linking early and late endpoints in adjuvant immunotherapy trials: an evaluation of multiple clinical outcomes.","authors":"","doi":"10.1093/oncolo/oyag399","DOIUrl":"10.1093/oncolo/oyag399","url":null,"abstract":"","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"31 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspirational autonomy and psychedelic-assisted therapy in advanced cancer: ethical lessons from clinical cases.","authors":"Keenan Wills Davis, Michelle C Bach, JoEllen Schimmels, Ali John Zarrabi","doi":"10.1093/oncolo/oyag402","DOIUrl":"10.1093/oncolo/oyag402","url":null,"abstract":"<p><p>Psychedelic-assisted therapy (PAT) is increasingly discussed as a potential intervention for anxiety, depression, and existential distress among patients with advanced cancer. Yet the ethical challenges of PAT for patients approaching the end of life remain underdeveloped, particularly for oncologists who may be asked to counsel patients or consider referral to clinical trials. This article uses 3 deidentified clinical vignettes from a clinical trial of psilocybin-assisted therapy in a palliative oncology context to examine what it means for PAT to \"work.\" We argue that PAT should not be evaluated only by symptom reduction or the production of mystical experiences, but also by whether it helps patients move toward valued forms of self-understanding, connection, courage, acceptance, or reconciliation. Drawing on the concept of \"aspirational autonomy,\" we propose that meaningful consent to PAT need not depend on full foreknowledge of an unpredictable experience. Rather, consent may be understood as a patient's endorsement of a supported process of moral and existential aspiration. We then identify practical ethical challenges for oncology, including expectation management, therapeutic ambiguity, somatic amplification, limited time for integration, and family dynamics. We conclude by offering candidate-selection considerations for oncologists, emphasizing aspirational clarity, cognitive and psychological stability, temporal feasibility, relational support, and realistic expectations.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durable response to vebreltinib in heavily pretreated MET-amplified intrahepatic cholangiocarcinoma: a case report.","authors":"Yingying Hang, Lu Bai, Hsiquan Hsu, Ying Chen, Fufeng Wang, Wuyan Xu, Xia Zhen, Zihao Wang, Yuan Li, Jun Qian","doi":"10.1093/oncolo/oyag409","DOIUrl":"10.1093/oncolo/oyag409","url":null,"abstract":"<p><strong>Background: </strong>MET amplification, although detected in only 2%-5% of intrahepatic cholangiocarcinomas (ICC), represents an actionable oncogenic driver. Treatment options after failure of first-line immunochemotherapy remain limited, and clinical data on vebreltinib, a novel highly selective MET inhibitor, in this molecular subset are scarce.</p><p><strong>Case presentation: </strong>A 61-year-old woman with metastatic ICC harboring high-level MET amplification (tissue gene copy number, 26.79) experienced disease progression on first-line durvalumab plus gemcitabine/cisplatin, second-line liposomal irinotecan/fluorouracil plus lenvatinib and durvalumab, radiotherapy, and transarterial chemoembolization. Following a brief period of vebreltinib (200 mg twice daily) plus durvalumab that was interrupted by grade 4 myelosuppression, the patient continued on vebreltinib monotherapy after hematologic recovery. Restaging computed tomography demonstrated a partial response (PR), with carbohydrate antigen 19-9 normalizing (a 99.2% reduction). This response lasted over 6 months until eventual disease progression.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first report of vebreltinib monotherapy inducing a deep and durable partial response in heavily pretreated, MET-amplified ICC, with the response lasting over 6 months despite eventual disease progression. This case underscores the critical value of comprehensive molecular profiling after first-line treatment failure to identify actionable drivers such as MET amplification.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}