Oncologist最新文献

{"title":"New tool in the toolbox: patient selection for zolbetuximab in advanced treatment-naïve gastric/gastroesophageal junction adenocarcinoma.","authors":"Udhayvir S Grewal, Timothy J Brown","doi":"10.1093/oncolo/oyaf185","DOIUrl":"10.1093/oncolo/oyaf185","url":null,"abstract":"<p><p>The treatment landscape for advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma has rapidly evolved over the last decade. The introduction of human epidermal growth factor receptor-2 (HER2)-targeted therapies and immune checkpoint inhibitors in combination with chemotherapy has led to significant improvements in overall survival in biomarker-selected patient populations. The recent Food and Drug Administration approval of zolbetuximab for patients with HER2-negative and Claudin-18 isoform 2 (CLDN18.2)-positive advanced or inoperable GEJ/gastric adenocarcinoma has introduced further complexity into frontline therapy decisions in the absence of direct head-to-head comparisons. Here, we review data from GLOW and SPOTLIGHT trials and discuss key tumor and patient characteristics and propose a therapeutic algorithm to help guide frontline treatment decisions for patients with advanced GEJ and gastric adenocarcinoma in light of the availability of zolbetuximab.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12242160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499344","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":"Colorectal cancer in pregnancy: case discussions and real-world data as well as literature review on current knowledge.","authors":"Suzanne Poulgrain, Ted Gibbons, Cian O'Leary, Sophie Feng, Vikram Jain, Connor Gerard O'Leary","doi":"10.1093/oncolo/oyaf097","DOIUrl":"10.1093/oncolo/oyaf097","url":null,"abstract":"<p><p>Colorectal cancer during pregnancy is a rare event; but given the well-recognized increasing incidence of young-onset colorectal cancer and delayed child-bearing seen in the Western world, it is anticipated to sharply increase in the next two decades. In this paper, the authors analyse three cases of colorectal cancer occurring in pregnancy, including the therapeutic approach and relevant outcomes. Two of the three cases received chemotherapy during pregnancy, all three children were born prematurely with one child having a significantly low birth weight. A review of our institution's referrals related to early-onset colorectal cancer (EOCRC) revealed a 50% increase in incidence in the last decade in line with worldwide trends of increase in this population. This paper also reviews the literature related to EOCRC in pregnancy and current diagnosis and management recommendations. Challenges with the therapeutic approach are experienced when symptoms are masked by the pregnancy, and when the diagnostic workup needs to weigh benefits to the mother with harms to the child. There is a clear and increasing need for consensus guidelines and further research into this field.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175856","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":"Immune-mediated adverse events in the randomized phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer.","authors":"Lorenzo Antonuzzo, Hidenori Takahashi, Joon Oh Park, Aumkhae Sookprasert, Roopinder Gillmore, Sheng-Shun Yang, Juan Cundom, Mila Petrova, Gina Vaccaro, Marielle Holmblad, Magdalena Żotkiewicz, Julie Wang, Nana Rokutanda, Do-Youn Oh","doi":"10.1093/oncolo/oyaf148","DOIUrl":"10.1093/oncolo/oyaf148","url":null,"abstract":"<p><strong>Introduction: </strong>We assessed immune-mediated adverse events (imAEs) in the TOPAZ-1 (NCT03875235) study of durvalumab plus gemcitabine and cisplatin (GemCis) in advanced biliary tract cancer (aBTC).</p><p><strong>Methods: </strong>Participants were randomized 1:1 to durvalumab (1500 mg) or placebo, plus GemCis (gemcitabine [1000 mg/m2] and cisplatin [25 mg/m2]) intravenously, followed by durvalumab (1500 mg) or placebo Q4W. We assessed imAE incidence, time to onset (TTO), and association with overall survival (OS).</p><p><strong>Results: </strong>In durvalumab (n = 338) versus placebo (n = 342), imAEs were reported in 13.9% versus 4.7% of participants, with median TTO of 127.0 versus 86.5 days, respectively. OS HR for durvalumab versus placebo in participants with imAEs was 0.59 (95% CI, 0.30-1.23) and was 0.83 (95% CI, 0.70-1.00) in participants without imAEs.</p><p><strong>Conclusions: </strong>Durvalumab demonstrated an OS benefit versus placebo in aBTC, irrespective of imAEs, which were mostly low grade and manageable. The results in these subgroups were consistent with the overall primary analysis.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03875235.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576980","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":"First-line treatment with HDACis plus tislelizumab combined with chemotherapy in advanced NSCLC: a single-arm phase II study.","authors":"Lijie Wang, Ming Gao, Ting Wang, Pengfei Cui, Guangying Chen, Xiao Han, Zhiqiang Ma, Wenyu Yang, Fangfang Jing, Junxun Ma, Fan Zhang, Haitao Tao, Yi Hu","doi":"10.1093/oncolo/oyaf155","DOIUrl":"10.1093/oncolo/oyaf155","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors in combination with chemotherapy have been a common first-line treatment for non-small cell lung cancer (NSCLC), but they do not work for all patients. HDAC inhibitors (HDACis) may synergize with progressive disease (PD)-1 antibodies by inducing and activating cellular immunity. In this phase II study, we assessed the efficacy and tolerability of chidamide and tislelizumab in combination with chemotherapy in NSCLC patients.</p><p><strong>Methods: </strong>This was a single-arm, prospective study. Driver-gene negative locally advanced and metastatic NSCLC patients without prior systemic treatment were enrolled. Patients received chidamide, tislelizumab, and chemotherapy for 4-6 cycles and were then maintained by tislelizumab and chidamide. The primary endpoint was objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response, overall survival (OS) and safety.</p><p><strong>Results: </strong>Twenty patients were enrolled in the study and most of them were PD-L1 1%-49% and PD-L1 < 1%. At the data cutoff, ORR was 80% (95% CI, 56.3-94.3), and DCR was 100%. The median follow-up was 23.4 months, the median PFS was 11.0 months (95% CI, 9.1-12.9m), and the median OS was 17.5 months (95% CI, 9.2-25.8m). Eleven patients (55.0%) had ≥ Grade 3 treatment-related adverse events (TRAEs). The most common ≥ Grade 3 TRAEs were leukopenia (25.0%) and neutropenia (20.0%). No patients died from treatment-related adverse events.</p><p><strong>Conclusions: </strong>The combination of HDACi and tislelizumab with chemotherapy showed promising antitumor effects and manageable toxicity. More studies are needed to further confirm these results.</p><p><strong>Clinicaltrials.gov identifier: </strong>ChiCTR2000041542.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592955","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":"How the addition of selinexor/bortezomib/dexamethasone as a Category 1 recommendation may erode outcomes.","authors":"Zena Chahine, Tomer Meirson, Shai Gilboa, Ghulam Rehman Mohyuddin","doi":"10.1093/oncolo/oyaf122","DOIUrl":"10.1093/oncolo/oyaf122","url":null,"abstract":"","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592956","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":"Regarding RECIST in retrospective studies.","authors":"Lawrence W Wu, LawrenceH Schwartz, Susan E Bates","doi":"10.1093/oncolo/oyaf182","DOIUrl":"10.1093/oncolo/oyaf182","url":null,"abstract":"","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512820","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":"First-in-human phase I open-label study of the LAG-3 antagonist antibody INCAGN02385 in patients with select advanced or metastatic solid tumors.","authors":"John D Powderly, Martin E Gutierrez, Ani S Balmanoukian, Paul E Hoyle, Zhiwan Dong, Lulu Cheng, Xuejun Chen, John E Janik, Nawel Bourayou, Omid Hamid","doi":"10.1093/oncolo/oyaf136","DOIUrl":"10.1093/oncolo/oyaf136","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint receptor lymphocyte-activation gene 3 (LAG-3) is an activation marker for CD4+ and CD8+ T cells. Prolonged LAG-3 expression downregulates T-cell activation; therefore, LAG-3 blockade may restore antitumor immune response. INCAGN02385 is a humanized monoclonal LAG-3-targeting antibody. This first-in-human phase I study evaluated INCAGN02385 for advanced/metastatic solid tumors.</p><p><strong>Materials and methods: </strong>In this dose escalation study, patients with select immunogenic advanced or metastatic solid tumors received a single INCAGN02385 infusion (25 mg to 750 mg) every 2 weeks (Q2W). Objectives included evaluation of safety/tolerability, maximum tolerated dose (MTD) (primary), pharmacokinetics (PK), antitumor activity (secondary).</p><p><strong>Results: </strong>Twenty-two patients were enrolled and treated. Sixty-four percent had received ≥ 3 lines of systemic therapy. Sixty-eight percent had received prior immune checkpoint inhibitor (ICI) therapy; anti-programmed death protein-1/anti-programmed death ligand-1, 68%, anti-cytotoxic T-lymphocyte-associated protein-4 therapy, 18%. No dose-limiting toxicities occurred, and an MTD was not reached. Sixteen patients (73%) experienced treatment-related adverse events (TRAEs), most frequently fatigue (n = 7). Except for one grade 3 lymphopenia TRAE, all were grade 1/2 severity. Two patients experienced sponsor-assessed immune-related AEs (pneumonitis, peripheral sensory neuropathy [n = 1] patient each). INCAGN02385 PK parameters were dose proportional across all doses evaluated. Six patients achieved stable disease lasting ≥ 56 days (range, 57-413 days).</p><p><strong>Conclusions: </strong>INCAGN02385 exhibited linear PK and preliminary evidence of disease control in this heavily pretreated population, consistent with other LAG-3-targeting monotherapies. A 350-mg Q2W dose was selected for phase II studies that will focus on combinations of INCAGN02385 with other ICIs.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592954","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":"Long-term efficacy and safety of pexidartinib in patients with tenosynovial giant cell tumor: final results of the ENLIVEN study.","authors":"Andrew J Wagner, William D Tap, Sebastian Bauer, Jean-Yves Blay, Jayesh Desai, Hans Gelderblom, Emanuela Palmerini, Christopher W Ryan, Charles Peterfy, John H Healey, Michiel van de Sande, Meng Qian, Dale E Shuster, Abdul Rajper, Xin Ye, Kristen Tecson, Margaret J Wooddell, Silvia Stacchiotti","doi":"10.1093/oncolo/oyae345","DOIUrl":"10.1093/oncolo/oyae345","url":null,"abstract":"<p><strong>Background: </strong>Pexidartinib is approved in the US, Taiwan, and Korea for adults with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery based on the phase III ENLIVEN study (NCT02371369). We report the final long-term efficacy and safety results from ENLIVEN.</p><p><strong>Methods: </strong>Adults with symptomatic TGCT not eligible for surgery were enrolled and randomized to pexidartinib or placebo (part 1). The blinded phase (part 1) ended at week 25; patients received pexidartinib (800 mg/day) until progression, toxicity, or study completion (part 2). This analysis includes patients who received pexidartinib at any time during ENLIVEN. Centrally reviewed overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and tumor volume score (TVS), time to response, duration of response (DOR), patient-reported outcomes (PROs), and long-term safety were assessed.</p><p><strong>Results: </strong>Overall, 91 patients received pexidartinib. With a median follow-up of 31.2 (range: 2-66) months, ORR was 60.4% and 68.1% by RECIST and TVS, respectively. Median DOR by RECIST was not reached (range: 0.03-63.4 months). Most responses were within the first 6 months of treatment; most responders were on 800 mg vs 600/400 mg dose levels, respectively. Throughout parts 1 and 2, 3 (3%) patients had progressive disease per RECIST without dose reduction/interruption. PROs improved or were maintained. The most common grade 3/4 treatment-emergent adverse events were aspartate aminotransferase (AST) increase (9%), alanine aminotransferase (ALT) increase (10%), and hypertension (8%). Twenty-eight (31%) patients had AST or ALT ≥3 times the upper limit of normal (ULN); 17 (19%) patients had AST or ALT ≥5 times the ULN. No new safety signals were observed after long-term pexidartinib treatment.</p><p><strong>Conclusions: </strong>Final long-term ENLIVEN results demonstrated that pexidartinib sustained clinical benefit, with increased ORR by RECIST and TVS compared to the end of the blinded phase at week 25. No new safety signals were reported.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561982","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":"Retrospective multicenter analysis of real-life toxicity and outcome of ipilimumab and nivolumab in metastatic uveal melanoma.","authors":"Amélie Ciernik, Laure Ciernik, Peter Bonczkowitz, Monika Morak, Lucie Heinzerling, Yacine Bennaceur, Aleigha Lawless, Ryan Sullivan, Julian Kött, Christoffer Gebhardt, Thomas J Carter, Paul Nathan, Sophie Tschopp, Reinhard Dummer, Egle Ramelyte","doi":"10.1093/oncolo/oyaf173","DOIUrl":"10.1093/oncolo/oyaf173","url":null,"abstract":"<p><strong>Background: </strong>Uveal melanoma (UM) is the most common primary ocular malignancy with a high rate of metastases. While immune checkpoint inhibitors (ICIs), including ipilimumab and nivolumab (ipi + nivo), have shown efficacy in metastatic cutaneous melanoma, their success in metastatic UM (MUM) remains limited. This study evaluates toxicity and outcomes of ipi + nivo in the largest, multicenter MUM cohort.</p><p><strong>Methods: </strong>We analyzed 131 MUM patients treated with ipi + nivo from 2016 to 2024 across 5 international centers. Rates of toxicity, response, and survival outcomes were assessed.</p><p><strong>Results: </strong>Among 131 patients, 37.4% of patients received 4 cycles of ipi + nivo. The most common reason for ipi + nivo discontinuation (31.3%) was toxicity. Of all treated patients, 80.2% experienced immune-related adverse events (irAEs). The overall response rate (ORR) was 16.4%, and the disease control rate (DCR) was 43.4%. Progression-free survival (PFS) was three months, and the median overall survival (OS) was 18 months. Patients receiving ipi + nivo as second-line therapy had lower ORR compared to patients who received ipi + nivo as first-line therapy (P = .04). Patients with exclusively extrahepatic metastases had a better ORR and OS compared to those with hepatic or mixed metastases (P = .02, P = .02, respectively). 20.6% of patients developed eosinophilia during treatment, which was associated with improved median OS (24 months vs 15 months, P = .02).</p><p><strong>Conclusions: </strong>Ipi + nivo shows moderate efficacy and clinically relevant toxicities in patients with MUM. Eosinophilia is a potential prognostic biomarker, that merits further investigation.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487176","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":"Moving the needle on immune checkpoint inhibitors with novel targets: are we being TIMid or LAGging behind?","authors":"Changsu Lawrence Park, Philippe L Bedard","doi":"10.1093/oncolo/oyaf145","DOIUrl":"10.1093/oncolo/oyaf145","url":null,"abstract":"","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592957","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}