Annals of Oncology最新文献

{"title":"Subcutaneous Versus Intravenous Pembrolizumab, in Combination With Chemotherapy, for Treatment of Metastatic Non-Small Cell Lung Cancer: The Phase 3 3475A-D77 Trial.","authors":"E Felip, C I Rojas, M Schenker, D M Kowalski, I A Casarini, T Csöszi, M A N Şendur, J Martins, A C Blanco, C-C Wang, X Song, R A L Ramirez Fallas, H Yoshioka, S Nair, M Wang, X Deng, M Lala, R Eiras, T Takahashi","doi":"10.1016/j.annonc.2025.03.012","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.012","url":null,"abstract":"<p><strong>Background: </strong>Pembrolizumab with berahyaluronidase alfa is for subcutaneous (SC) administration. The phase 3 open-label 3475A-D77 study (NCT05722015) assessed SC pembrolizumab versus intravenous (IV) pembrolizumab, plus chemotherapy, for treatment of metastatic non-small-cell lung cancer (mNSCLC).</p><p><strong>Participants and methods: </strong>Participants with newly diagnosed stage IV squamous or nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations were randomized 2:1 to pembrolizumab SC 790 mg every 6 weeks (Q6W) or pembrolizumab IV 400 mg Q6W (18 cycles), each given with platinum doublet chemotherapy. Dual primary endpoints were pharmacokinetics exposure measures of cycle 1 area-under-the-curve (AUC_0-6wks) and steady-state trough concentration (C_trough) of pembrolizumab. The noninferiority margin for AUC_0-6wks and C_trough geometric mean ratios (GMR) of pembrolizumab SC versus IV was specified as 0.8. Secondary endpoints included additional pharmacokinetics exposure measures, pembrolizumab immunogenicity, efficacy, and safety.</p><p><strong>Results: </strong>377 participants were randomized to the pembrolizumab SC (n=251) or IV (n=126) arms. Median time from randomization to data cutoff (12Jul2024) was 9.6 months (range 6.2-16.4). Median injection time for pembrolizumab SC was 2.0 minutes (range 1-12). The GMR (96% CI) for cycle 1 AUC_0-6wks was 1.14 (1.06-1.22); P<0.0001. The GMR (94% CI) for steady-state C_trough was 1.67 (1.52-1.84); P<0.0001. Secondary pharmacokinetics endpoints were within established bounds for pembrolizumab. Anti-pembrolizumab antibodies were detected in 1.4% (pembrolizumab SC arm) and 0.9% (pembrolizumab IV arm) of participants. For the pembrolizumab SC versus IV arms, objective response rates were 45.4% vs 42.1% (ORR ratio 1.08, 95% CI 0.85-1.37). Other efficacy measures were similar and safety profiles were consistent between treatment arms.</p><p><strong>Conclusions: </strong>Overall exposure and trough concentrations of pembrolizumab SC 790 mg Q6W were noninferior to those of pembrolizumab IV 400 mg Q6W given with chemotherapy in participants with treatment-naïve mNSCLC. Results support pembrolizumab SC as a treatment option in all indications where pembrolizumab IV can be used.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741885","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":"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":"S Loibl, M Martin, H Bonnefoi, M Untch, S Kim, H D Bear, J A García-Sáenz, M M Olivé, N Mc Carthy, K Gelmon, C M Kelly, S-A Im, T Reimer, M-J Noelia, Z Zhang, M Toi, L Provencher, H S Rugo, M Gnant, A Makris, A A Torres, N Hirmas, J Holtschmidt, V Nekljudova, F Marmé","doi":"10.1016/j.annonc.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.010","url":null,"abstract":"<p><strong>Background: </strong>The addition of 1-year of palbociclib to endocrine therapy (ET) did not improve invasive disease-free survival (iDFS) compared to placebo in the PENELOPE-B trial. Here we report the final survival results for the PENELOPE-B trial.</p><p><strong>Methods: </strong>The PENELOPE-B trial investigated whether adding 1 year of palbociclib to ET in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) patients with residual disease and high relapse risk (CPS-EG score ≥3 or 2 and ypN+) after taxane-based neoadjuvant chemotherapy would improve patient survival. Patients (n=1250) were randomly assigned to receive either palbociclib 125 mg or placebo d1-21 q4w for 13 cycles in addition to ET.</p><p><strong>Results: </strong>After a median follow-up of 77.8 months, we recorded 225 deaths (108 palbociclib; 117 placebo) with 6-year overall survival (OS) rate of 82.4% in the palbociclib arm vs. 80.3% in the placebo arm [hazard rationHR0.87, 95% CI 0.67-1.14, p=0.31]. No significant improvement was noted for palbociclib vs placebo for iDFS, distant disease-free survival (DDFS) or locoregional relapse rate (LRR), even with longer follow-up. Upon stratified analysis, we found no benefits across major subgroups. However, exploratory post-hoc analyses of the lobular BC (LBC) subgroup indicated a trend towards better survival outcomes in favour of palbociclib HR of 0.45 (95% CI 0.19-1.07, p=0.062) for OS and 0.52 (95% CI 0.28-0.97, p=0.035) for iDFS.</p><p><strong>Conclusion: </strong>The study concluded that palbociclib did not significantly improve survival outcomes in the overall population. Exploratory post-hoc analyses suggested a trend towards better iDFS outcome in patients with lobular breast cancer receiving palbociclib.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727488","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":"Progression-free survival: a true endpoint in first-line treatment for classic Hodgkin Lymphoma?","authors":"N. Yamauchi,&nbsp;D. Maruyama","doi":"10.1016/j.annonc.2025.02.004","DOIUrl":"10.1016/j.annonc.2025.02.004","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 356-358"},"PeriodicalIF":56.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679121","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":"“Biomarker analyses from randomized trials in clear cell renal cell carcinoma”","authors":"S. Coca Membribes,&nbsp;T. Powles","doi":"10.1016/j.annonc.2025.02.012","DOIUrl":"10.1016/j.annonc.2025.02.012","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 353-355"},"PeriodicalIF":56.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679123","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":"Enrichment of CD7⁺CXCR3⁺ CAR T cells in infusion products is associated with durable remission in relapsed or refractory diffuse large B-cell lymphoma.","authors":"R Bartolini, L Trueb, D Daoudlarian, V Joo, A Noto, R Stadelmann, B Gentner, C Fenwick, M Perreau, G Coukos, G Pantaleo, C Arber, M Obeid","doi":"10.1016/j.annonc.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.011","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor (CAR) T-cell therapy is the standard of care for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, more than half of patients fail to achieve durable remission. Identifying predictive biomarkers within the CAR T-cell infusion product (IP) may guide strategies to improve clinical outcomes.</p><p><strong>Patients and methods: </strong>This single-center observational study conducted at Lausanne University Hospital (CHUV), Switzerland, analyzed IPs from 13 patients with R/R DLBCL who underwent standard-of-care CAR T-cell therapy. A 39-marker mass cytometry panel was used to compare phenotypic and functional markers between long-term responders (R) and non-responders (NR). Unsupervised and supervised analytic approaches were applied to IP data, and longitudinal peripheral blood samples were collected over 30 days post-infusion to track CAR T-cell subpopulation dynamics.</p><p><strong>Results: </strong>At a median follow-up of 13·5 months, median progression-free survival (PFS) was 13·3 months (95% CI 9·7-24·3) in R (n=8) versus 3·5 months (95% CI 0·5-5·4) in NR (n=5) (hazard ratio 56·67 [95% CI 7·3-439·3]; p=0·0001). A CD3⁺CXCR3⁺CD7⁺ CAR T-cell subpopulation-found in both CD4⁺ and CD8⁺ compartments-was significantly enriched in R. These cells showed increased expression of perforin, granzyme B, and NKG2D (restricted to CD8⁺ cells). In contrast, NR had a higher frequency of CXCR3⁺CD7⁺LAG3⁺ CAR T-cells. Surface expression of CD3, CD7, CXCR3, and NKG2D were higher in R, whereas LAG3, Ki67, and CD71 were elevated in NR. A predictive cut-off ratio of CD3⁺CXCR3⁺CD7⁺LAG3⁺CAR⁺ T-cells <0·83 and CD3⁺CXCR3⁺CD7⁺NKG2D⁺CAR⁺ T-cells >1·034 yielded a predictive accuracy of 0·92. Serum CXCL9 and CXCL10 concentrations did not differ between groups.</p><p><strong>Conclusion: </strong>Enrichment of CD7⁺CXCR3⁺ CAR T-cells alongside elevated NKG2D expression in R, in contrast to higher LAG3 and CD71 in NR, emerged as potentially robust correlates of therapeutic outcome. Although derived from a small, hypothesis-generating cohort, these findings suggest that targeted analysis of IP composition may inform the development of biomarker-driven strategies to optimize CAR T-cell products and improve the likelihood of durable remission in R/R DLBCL.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708250","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":"Advancing ctDNA detection: Using whole-genome sequencing to power minimal residual disease monitoring in breast cancer.","authors":"L Andersen, N J Birkbak","doi":"10.1016/j.annonc.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.008","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690499","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":"The impact of the immunological context on outcomes of solid cancer patients treated with genotype-matched targeted therapies: a comprehensive review.","authors":"O Mubarak, G Middleton","doi":"10.1016/j.annonc.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.007","url":null,"abstract":"<p><strong>Introduction: </strong>Outcomes with genotype-matched targeted therapy in solid cancer patients are heterogeneous: some have exceptional responses, others primary progression. This review explores the immunobiological features which may underlie this differential response.</p><p><strong>Methods: </strong>We conducted a literature review of studies assessing impact of immune context following searches on Web of Science, Medline and Embase. Relevant outcomes include response, progression-free survival and overall survival. Data was extracted from multivariate analysis, univariate analysis or directly from Kaplan-Meier curves. Meta-analyses were performed where three or more studies analysed the same immune factor for the same cancer type. Remaining studies were analysed descriptively.</p><p><strong>Results: </strong>In the adjuvant setting assessment of the immune context does not highlight a group failing to derive benefit for the use of dabrafenib/trametinib after resection of BRAFV600E melanoma Differential gene expression in exceptional responders show enrichment of genes associated with immune activation. BRAFV600E colorectal cancer patients with high cytolytic scores benefit from the addition of MEK inhibition whereas those with low scores fare better without. High PD-L1 expression is predictive of inferior outcomes to EGFR, ALK and G12C tyrosine kinase inhibitors. EGFR-mutant patients with high CD8+ T cells and PD-L1 positivity have very poor outcomes. Stromal tumour-infiltrating lymphocytes predicts for efficacy of stromal-poor tumours in HER-2+ breast cancer treated with short-course adjuvant trastuzumab. High immune metagene and single immune gene expression is predictive of benefit for chemotherapy plus trastuzumab, but not chemotherapy alone. The addition of pertuzumab or lapatanib appears to be beneficial in those with immune non-enriched microenvironments. High MHCI is negatively and high MHCII positively predictive of outcome with trastuzumab-based therapy.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first review assessing immunological context as biomarker for targeted therapy. The results of this review represent an important resource to aid future translational studies in advancing stratified precision medicine oncology.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673186","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":"Challenges and Opportunities of Emerging Mechanisms of Resistance to KRAS^G12C Inhibitors.","authors":"M Cecchini, P LoRusso","doi":"10.1016/j.annonc.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.009","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673184","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-Survival among patients treated with total mesorectal excision or selective watch-and-wait after total neoadjuvant therapy: a pooled analysis of the CAO/ARO/AIO-12 and OPRA randomized phase II trials.","authors":"R O Perez, B B Vailati, G P São Julião, L E Corbi","doi":"10.1016/j.annonc.2025.03.003","DOIUrl":"10.1016/j.annonc.2025.03.003","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633424","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":"European cancer mortality predictions for the year 2025 with focus on breast cancer","authors":"C. Santucci ,&nbsp;S. Mignozzi ,&nbsp;F. Levi ,&nbsp;M. Malvezzi ,&nbsp;P. Boffetta ,&nbsp;E. Negri ,&nbsp;C. La Vecchia","doi":"10.1016/j.annonc.2025.01.014","DOIUrl":"10.1016/j.annonc.2025.01.014","url":null,"abstract":"<div><h3>Background</h3><div>We predicted the number of cancer deaths and rates for 2025 in the European Union (EU), its five most populous countries, and the UK, focusing on breast cancer.</div></div><div><h3>Materials and methods</h3><div>We derived population data and death certificates for all cancers and major sites for the EU, France, Germany, Italy, Poland, Spain, and the UK since 1970, from the World Health Organization and United Nations databases. Estimates for 2025 were computed by linear regression on recent trends identified through Poisson joinpoint regression, considering the slope of the most recent trend segment. Deaths averted from 1989 to 2025 were calculated by applying the 1988 peak rate to subsequent population data.</div></div><div><h3>Results</h3><div>We estimated 1 280 000 cancer deaths in the EU in 2025, corresponding to age-standardised rates (ASRs) of 120.9/100 000 males (−3.5% versus 2020) and 79.1/100 000 females (−1.2%). In the UK, we predicted 173 000 cancer deaths and ASRs of 101.2/100 000 males (−10.1%) and 82.1/100 000 females (−6.3%). In the EU, favourable trends are predicted for major neoplasms, except pancreatic cancer, in males (+2.0%) and females (+3.0%), and lung (+3.8%) and bladder (+1.9%) cancers among females. Breast cancer mortality showed favourable trends in all countries. Substantial decreases were predicted for EU females aged 50-69 years (−9.8%) and 70-79 years (−12.4%). Between 1989 and 2025, we estimated about 6.8 million averted cancer deaths in the EU, including over 373 000 breast cancer deaths. Corresponding numbers for the UK were 1 500 000 and 197 000.</div></div><div><h3>Conclusion</h3><div>EU breast cancer rates have fallen by 30% since 1990, due to advances in prevention, treatment, and early detection. Contrasting trends in lung cancer among males and females reflect differing tobacco smoking patterns. Female lung cancer mortality is still increasing in the EU, though less than in the previous decade. Persistent unfavourable pancreatic cancer trends can be related to the increasing prevalence of obesity and limited therapeutic advances, requiring continued attention.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 460-468"},"PeriodicalIF":56.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}