Annals of Oncology最新文献

{"title":"Twenty year survival of advanced gastrointestinal stromal tumours treated with imatinib Exploratory long-term follow-up of the BFR14 trial.","authors":"J-Y Blay, Q Devin, M Toulmonde, A Dufresne, N Penel, A Adenis, M Rios, F Bertucci, F Duffaud, N Firmin, T Valentin, E Bompas, O Collard, M Pracht, A Hervieu, B Verret, I Ray-Coquard, P Cassier, C Henon, D Perol, A Italiano, S Chabaud, A Le Cesne","doi":"10.1016/j.annonc.2025.05.535","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.535","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal stromal tumors (GIST) are driven in >75% of patients by mutations in KIT and PDGFRA kinases. Imatinib, a tyrosine kinase inhibitor, has shown efficacy in metastatic GIST but the long-term survival impact remains less understood, especially after extended treatment durations.</p><p><strong>Methods: </strong>The BFR14 study, initiated in 2002, is a multicentric randomized phase III clinical trial involving 434 patients with advanced or unresectable GIST, treated with imatinib. This long-term follow-up aimed to assess the survival outcomes of the patients prospectivey included in this study. Patient demographics, mutation status, overall survival (OS) and response rates were collected.</p><p><strong>Results: </strong>With a median follow-up of 219 months, median OS was 75.3 months. Survival rates at 10, 15, and 20 years were 33.9%, 19.8%, and 13.1%, respectively. Factors significantly associated with better survival included female gender, gastric tumor location, smaller primary tumor size, and KIT exon 11 mutations. Complete remission to imatinib and complete surgical resection of metastases with R0 resections are associated with a doubling of median survival and and asignificanty prolonged OS.</p><p><strong>Conclusion: </strong>This long term follow-up of the BFR14 trial shows long-term efficacy of imatinib in patients with advanced GIST. Complete resection of metastasis and achievement of complete response is associated with a doubling of median survival.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor 'A pooled analysis of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with brain metastases' by F. André et al.","authors":"Yi Liu, Chuanhao Zhang, Yi Liu","doi":"10.1016/j.annonc.2025.05.532","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.532","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ESMO-Magnitude of Clinical Benefit Scale version 2.0 (ESMO-MCBS v2.0).","authors":"N I Cherny, S F Oosting, U Dafni, N J Latino, M Galotti, P Zygoura, G Dimopoulou, T Amaral, J Barriuso, A Calles, B Kiesewetter, C Gomez-Roca, B Gyawali, M Piccart, A Passaro, F Roitberg, N Tarazona, D Trapani, G Curigliano, R Wester, G Zarkavelis, C Zielinski, E G E de Vries","doi":"10.1016/j.annonc.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.04.006","url":null,"abstract":"<p><strong>Background: </strong>The ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated tool to assess the magnitude of clinical benefit from new cancer therapies, with planned updates based upon recognition of new needs and shortcomings. This paper describes the development of ESMO-MCBS v2.0.</p><p><strong>Methodology: </strong>The revision process incorporates nine steps: (i) review of critiques and suggestions and identification of problems in the application of ESMO-MCBS v1.1; (ii) identification of shortcomings for revision in the upcoming version; (iii) drafting solutions addressing identified shortcomings; (iv) field-testing of solutions; (v) preparation of a near-final revised version for peer review for reasonableness by members of the ESMO Faculty and ESMO Guidelines Committee; (vi) amendments based on peer review for reasonableness; (vii) near-final review by members of the ESMO-MCBS Working Group; (viii) final amendments; (ix) final review and approval by members of the ESMO-MCBS Working Group and the ESMO Executive Board.</p><p><strong>Results: </strong>Seventeen issues for revision or amendment were considered, and 13 amendments were formulated to address identified shortcomings. In the curative setting, studies evaluated based on disease-free survival now credit improved time without treatment or disease even when overall survival is not significantly improved, and studies with small absolute gain in disease-free survival are credited more conservatively. Additionally, acute and persistent toxicity annotations are added. In the non-curative setting, the approach to crediting a difference in the tail of overall survival and progression-free survival curves is more statistically valid, and the toxicity evaluation has been revised. In peer review all amendments were found to be either reasonable or mostly reasonable. The amendments changed the scoring of 85/353 of evaluated studies.</p><p><strong>Conclusions: </strong>The amendments incorporated into ESMO-MCBS v2.0 change the scores of 13.6% of evaluated studies (10.5% downgraded, 3.1% upgraded) and add toxicity annotations to 45.5% of the studies in the curative setting, and improve its discriminatory capacity and utility.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor - Final Survival Results from the Penelope-B trial investigating palbociclib vs placebo for patients with high-risk HR+/HER2- breast cancer and residual disease after neoadjuvant chemotherapy - PENELOPE-B.","authors":"Taha Koray Sahin, Deniz Can Guven","doi":"10.1016/j.annonc.2025.05.531","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.531","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatio-temporal T cell tracking for personalized TCR-T designs in childhood cancer.","authors":"I Sentís, J L Melero, A Cebria-Xart, M Grzelak, M Soto, A Michel, Q Rovira, C J Rodriguez-Hernandez, G Caratù, A Urpi, C Sauvage, A Mendizabal-Sasieta, D Maspero, C E Lavarino, A Pascual-Reguant, A Castañeda Heredia, J P Muñoz Perez, J Mora, A Harari, J C Nieto, A Avgustinova, H Heyn","doi":"10.1016/j.annonc.2025.05.530","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.530","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibition (ICI) has revolutionized oncology, offering extended survival and long-term remission in previously incurable cancers. While highly effective in tumors with high mutational burden, lowly mutated cancers, including pediatric malignancies, present low response rate and limited predictive biomarkers.</p><p><strong>Patients and methods: </strong>We present a framework for the identification and validation of tumor-reactive T cells as a biomarker to quantify ICI efficacy and as candidates for a personalized TCR-T cell therapy. Therefore, we profiled a pediatric malignant rhabdoid tumor patient with complete remission after ICI therapy using deep single-cell T cell receptor (TCR) repertoire sequencing of the tumor microenvironment (TME) and the peripheral blood.</p><p><strong>Results: </strong>Tracking T cell dynamics longitudinally from the tumor to cells in circulation over a time course of 12 months revealed a systemic response and durable clonal expansion of tumor-resident and ICI-induced TCR clonotypes. We functionally validated tumor reactivity of TCRs identified from the TME and the blood by co-culturing patient-derived tumor cells with TCR-engineered autologous T cells. Here, we observed unexpectedly high frequencies of tumor-reactive TCR clonotypes in the TME and confirmed T cell dynamics in the blood post-ICI to predict tumor-reactivity.</p><p><strong>Conclusion: </strong>These findings strongly support spatio-temporal tracking of T cell activity in response to ICI to inform therapy efficacy and to serve as a source of tumor-reactive TCRs for personalized TCR-T designs.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the circulating lipid panel, PCPro, with clinical outcomes in metastatic hormone-sensitive prostate cancer: post-hoc analysis of the ENZAMET Phase 3 randomised trial (ANZUP 1304).","authors":"H-M Lin, T Scheinberg, N Portman, R M N Kim, R Mellor, K Hunyh, A N Faulkner, N A Mellett, I D Davis, A Martin, D Sullivan, A Joshua, M McJannett, V Subhash, S Yip, A A Azad, I C Marschner, S A North, R S McDermott, K N Chi, M R Stockler, C J Sweeney, P J Meikle, L G Horvath","doi":"10.1016/j.annonc.2025.05.529","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.529","url":null,"abstract":"<p><strong>Background: </strong>Enzalutamide significantly improves overall survival (OS) of patients with metastatic hormone- sensitive prostate cancer (mHSPC). However, ∼10% of patients will die within 2 years. PCPro is a plasma lipid panel associated with decreased OS in metastatic castration-resistant prostate cancer. In this study, we assessed the association between PCPro and clinical outcomes in mHSPC by performing a post-hoc analysis of ENZAMET, the landmark phase 3 trial comparing enzalutamide to non-steroidal anti-androgen (NSAA).</p><p><strong>Patients and methods: </strong>PCPro status was determined by liquid chromatography-mass spectrometry analysis of plasma samples from 866 participants (77% of ENZAMET trial cohort), before treatment (n=866) and at first progression (n=282). Outcomes examined were OS and clinical progression-free survival (clinPFS).</p><p><strong>Results: </strong>Participants with a positive PCPro status at baseline (13.4%), had significantly shorter OS and clinPFS compared to those with a negative PCPro status (OS HR=1.81; clinPFS HR=1.65; p<0.0001). PCPro is an independent prognostic factor when modelled with key clinical prognostic factors (p<0.001). Enzalutamide (compared to NSAA) improved the OS of PCPro-negative participants (HR = 0.61, p<0.0001), but not the survival of PCPro-positive participants (HR=1.10, p=0.69; interaction p=0.024). Participants, who were PCPro-positive at progression, have shorter OS than those who were negative, irrespective of baseline status (median OS 24-28 months versus 42-45 months).</p><p><strong>Conclusion: </strong>PCPro status is a prognostic biomarker and predictive of the lack of OS benefit from enzalutamide compared to NSAA in mHSPC. These findings provide a rationale for testing therapeutic agents that can modify circulating lipid profiles in mHSPC.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.","authors":"R-D Hofheinz, E Fokas, L Benhaim, T J Price, D Arnold, R Beets-Tan, M G Guren, G A P Hospers, S Lonardi, I D Nagtegaal, R O Perez, A Cervantes, E Martinelli","doi":"10.1016/j.annonc.2025.05.528","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.528","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab plus enzalutamide and androgen deprivation therapy versus placebo plus enzalutamide and androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: the randomized, double-blind, phase III KEYNOTE-991 study.","authors":"C Gratzke, M Özgüroğlu, A Peer, M A N Sendur, M Retz, J C Goh, W Loidl, G Jayram, S-S Byun, C Kwak, M Kwiatkowski, R M Kopp, J C V Limón, J F E Penagos, U De Giorgi, K M da Trindade, C Niu, Y Liu, C H Poehlein, J M Piulats","doi":"10.1016/j.annonc.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.008","url":null,"abstract":"<p><strong>Background: </strong>Despite treatment advances, most patients with metastatic hormone-sensitive prostate cancer (mHSPC) experience disease progression to castration-resistant disease within 5 years. The placebo-controlled, double-blind, phase III KEYNOTE-991 study evaluated the efficacy and safety of adding pembrolizumab to enzalutamide and androgen deprivation therapy (ADT) in participants with mHSPC.</p><p><strong>Patients and methods: </strong>Eligible participants were aged ≥18 years with next-generation hormonal agent‒naive mHSPC. Participants were randomly assigned (1:1) to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for ≤35 cycles, with oral enzalutamide 160 mg and continuous ADT. Primary end points were radiographic progression-free survival (rPFS) and overall survival. Safety was a secondary end point.</p><p><strong>Results: </strong>Between March 2, 2020, and August 9, 2021, 626 participants were randomly assigned to pembrolizumab plus enzalutamide and ADT and 625 participants to placebo plus enzalutamide and ADT. At the first interim analysis, the median follow-up was 21.1 months (range, 14.8-32.0 months). rPFS was not superior with pembrolizumab versus placebo (median not reached in both arms; hazard ratio, 1.20 [95% confidence interval (CI), 0.96 to 1.49]; P = 0.9467). Median overall survival was not reached in either arm (hazard ratio, 1.16 [95% CI, 0.88 to 1.53]; not formally statistically tested per the multiplicity strategy). Grade ≥3 adverse events (AEs) and serious AEs were reported in 61.9% versus 38.1% and 40.3% versus 23.2% of participants in the pembrolizumab versus the placebo arm, respectively. Any-grade rash occurred at a higher frequency with pembrolizumab (25.1%) versus placebo (9.3%).</p><p><strong>Conclusion: </strong>KEYNOTE-991 did not meet its primary end point and was stopped for futility. The addition of pembrolizumab to enzalutamide and ADT was associated with higher frequencies of grade ≥3 AEs and serious AEs than with placebo. Rash was identified as an additional safety signal with pembrolizumab plus enzalutamide and ADT.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab plus enzalutamide versus placebo plus enzalutamide for chemotherapy-naive metastatic castration-resistant prostate cancer: the randomized, double-blind, phase III KEYNOTE-641 study.","authors":"J N Graff, M Burotto, P C Fong, D W Pook, B Zurawski, R M Kopp, J Salinas, K A Bylow, G Kramer, R Ratta, M Kwiatkowski, M Retz, C Kwak, J A Arranz Arija, H Gurney, N Matsubara, L Villanueva, T Todenhöfer, L W Liang, J Todoric, K Imai, A Stenzl","doi":"10.1016/j.annonc.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.007","url":null,"abstract":"<p><strong>Background: </strong>Established first- and second-line standard-of-care treatment options (abiraterone, enzalutamide, taxane chemotherapy) are available for patients with metastatic castration-resistant prostate cancer (mCRPC), but almost all patients experience subsequent disease progression. The randomized, double-blind, phase III KEYNOTE-641 study evaluated pembrolizumab plus enzalutamide versus placebo plus enzalutamide in participants with chemotherapy-naive mCRPC.</p><p><strong>Patients and methods: </strong>Eligible participants were males aged ≥18 years with confirmed mCRPC and no prior chemotherapy except docetaxel in the hormone-sensitive setting. Prior abiraterone treatment was permitted. Participants were randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo intravenously once every 3 weeks for ≤35 cycles plus enzalutamide 160 mg orally daily. Dual primary end points were overall survival (OS) and radiographic progression-free survival (rPFS) per PCWG-modified RECIST v1.1 by blinded independent central review. Safety was a secondary end point.</p><p><strong>Results: </strong>Between August 21, 2019, and June 10, 2022, 1244 participants were randomly assigned to pembrolizumab plus enzalutamide (n=621) or placebo plus enzalutamide (n=623). At the data cutoff date (December 12, 2022), median follow-up was 27.6 months (range, 6.1-39.8 months). Primary end points of OS (median, 24.7 vs 27.3 months; hazard ratio [HR], 1.04 [95% CI, 0.88-1.22]; P=0.66) and rPFS (median, 10.4 vs 9.0 months; HR, 0.98 [0.84-1.14]; P=0.41) with pembrolizumab plus enzalutamide versus placebo plus enzalutamide were not met. The prespecified boundary for futility for OS was crossed, and the study was stopped. Grade ≥3 treatment-related adverse events occurred in 192 of 615 participants (31.2%) with ≥1 dose of pembrolizumab plus enzalutamide and in 67 of 620 participants (10.8%) with ≥1 dose of placebo plus enzalutamide. Seventy-one (11.5%) and 21 (3.4%) participants, respectively, discontinued study treatment due to treatment-related adverse events.</p><p><strong>Conclusion: </strong>Adding pembrolizumab to enzalutamide did not improve efficacy outcomes for participants with chemotherapy-naive mCRPC. Additional toxicity was observed with the combination regimen.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintenance treatment in sarcomas: who is it for?","authors":"A Constantinidou, R L Jones","doi":"10.1016/j.annonc.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.05.002","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}