Annals of Oncology最新文献

{"title":"Final overall survival and safety analyses of the phase 3 PSMAfore trial of [¹⁷⁷Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer.","authors":"K Fizazi, K N Chi, N D Shore, K Herrmann, J S de Bono, D Castellano, J M Piulats, A Fléchon, X X Wei, H Mahammedi, G Roubaud, M Fleming, T Haas, S Ghebremariam, T N Kreisl, S Rajagopalan, O Sartor, M J Morris","doi":"10.1016/j.annonc.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.07.003","url":null,"abstract":"<p><strong>Background: </strong>In PSMAfore, [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) prolonged radiographic progression-free survival (rPFS) in taxane-naive patients with metastatic castration-resistant prostate cancer (mCRPC), with a favourable safety profile, versus a change in androgen receptor pathway inhibitor (ARPI). We report the final overall survival (OS) analysis and updated safety data.</p><p><strong>Patients and methods: </strong>PSMAfore (NCT04689828) was an open-label, international, phase 3 trial. Patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who had experienced disease progression once on a previous ARPI and were candidates for ARPI change were randomized 1:1 to ¹⁷⁷Lu-PSMA-617 or ARPI change to abiraterone or enzalutamide. Crossover from ARPI change to ¹⁷⁷Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. Endpoints included rPFS (primary), OS (key secondary), and safety (secondary).</p><p><strong>Results: </strong>Patients were randomized to ¹⁷⁷Lu-PSMA-617 or ARPI change (n = 234 each): 141/234 participants (60.3%) randomized to ARPI change crossed over (75.4% of those with centrally confirmed radiographic progression). The median OS was 24.48 months (95% CI 19.55-28.94) with ¹⁷⁷Lu-PSMA-617 versus 23.13 (19.61-25.53) with ARPI change (hazard ratio [HR] 0.91 [95% CI 0.72-1.14]; p = 0.20) based on the intention-to-treat (ITT) principle; the crossover-adjusted OS HR by inverse probability of censoring weighting modelling was 0.59 (95% CI 0.38-0.91). For ¹⁷⁷Lu-PSMA-617 versus ARPI change, exposure-adjusted incidences of grade ≥ 3 and serious treatment-emergent adverse events were 60.8 versus 85.1 and 32.5 versus 49.9 per 100 patient-treatment years, respectively. Dry mouth occurred in 135/227 participants (59.5%; 2/227 grade ≥ 3) and anaemia in 62/227 (27.3%; 14/227 grade ≥ 3) in the ¹⁷⁷Lu-PSMA-617 arm.</p><p><strong>Conclusions: </strong>OS analyses did not show a statistically significant difference between the ¹⁷⁷Lu-PSMA-617 and ARPI arms based on the ITT principle; results were likely confounded by the high rate of crossover. The safety profile of ¹⁷⁷Lu-PSMA-617 was favourable with no new safety signals identified.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666841","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":"Fracture-related hospitalisations in newly diagnosed high-risk localised or metastatic hormone-sensitive prostate cancer: secondary analysis of the STAMPEDE phase 3 trials of docetaxel and zoledronic acid using healthcare systems data.","authors":"C Jones, P Dutey-Magni, L R Murphy, M L Murray, J E Brown, E McCloskey, M Brown, C L Amos, D C Gilbert, R J Jones, W Cross, D Matheson, R Millman, M K B Parmar, G Attard, M R Sydes, L C Brown, N D James, N W Clarke, A Sachdeva","doi":"10.1016/j.annonc.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.07.005","url":null,"abstract":"<p><strong>Background: </strong>Androgen deprivation therapy (ADT), the mainstay systemic treatment for high risk non-metastatic (M0) and metastatic (M1) prostate cancer (PCa) is associated with bone loss and increased fracture risk. The STAMPEDE trial tested the addition of zoledronic acid ± docetaxel (with prednisolone) to ADT. Both regimens may impact bone health. However, long-term fracture incidence remains uncertain.</p><p><strong>Patients and methods: </strong>Health systems data were obtained for pts recruited from England and randomised to standard-of-care (SOC) ADT compared with SOC plus zoledronic acid or docetaxel or both docetaxel and zoledronic acid. ICD10 diagnosis and OPCS procedure codes from inpatient hospital admissions were used to identify fracture-related hospitalisations (FRH). Flexible parametric competing risks models were used to estimate 5- and 10-year cumulative incidence and sub-distribution hazard ratios (SDHR).</p><p><strong>Results: </strong>2,140 of 2,705 (79%) pts recruited from trial sites in England were eligible for this secondary analysis. Linked data were available for 2,042/2,140 (96%) pts (734 M0, 1,308 M1). 5-year cumulative incidence of fracture for M0 and M1 pts treated with SOC only was 11% (95% CI, 8-15%) and 23% (95% CI, 19-28%) respectively. 10-year cumulative incidence in M0 pts was 26% (95% CI, 20-33%). Allocation to zoledronic acid significantly reduced the risk of fracture in M1 pts (SDHR 0.73, 95% CI 0.55-0.97; p=0.015) but not M0 pts (SDHR 0.88, 95% CI 0.59-1.32; p=0.549). Docetaxel had no clear effect on the risk of fracture in M0 (p=0.570) or M1 (p=0.264) pts.</p><p><strong>Conclusions: </strong>High cumulative incidence of fracture was observed in both non-metastatic and metastatic PCa patients receiving ADT. The addition of zoledronic acid to ADT ± docetaxel significantly reduced long-term fracture risk in metastatic participants but had no clear effect in non-metastatic disease. These data support the use of bone protective agents to reduce fracture risk in men with metastatic prostate cancer undergoing ADT.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666842","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":"Re-examining Post-operative Chemoradiotherapy in Head and Neck Cancer: An Updated Long-Term Combined Analysis of RTOG 9501/EORTC 22931.","authors":"Z S Zumsteg, M Luu, C Fortpied, J K Jang, M M Chen, J Mallen-St Clair, E Walgama, Q T Le, M Machtay, S Tribius, A Forastiere, S Wong, E Mahmut Ozsahin, V Gregoire, J B Vermorken, A S Ho, S S Yom","doi":"10.1016/j.annonc.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.07.004","url":null,"abstract":"<p><strong>Background: </strong>Post-operative chemoradiation (CRT) is generally recommended for patients with extranodal extension (ENE) and/or positive margins, but not for patients without these features, based on a post-hoc analysis of RTOG 9501 and EORTC 22931. However, this analysis lacked tests of interaction necessary to identify a predictive biomarker. In addition, updated data is now available.</p><p><strong>Patients: </strong>This study assessed 744 patients enrolled on RTOG 9501 and EORTC 22931, randomized trials comparing CRT to RT following surgery. Overall survival (OS) was analyzed with Cox regression. Cancer-specific mortality (CSM), other-cause mortality (OCM), and recurrence outcomes were analyzed with competing risk methodology. Tests of interaction assessed for differential benefits of CRT in various subgroups.</p><p><strong>Results: </strong>Median follow-up was 6.9 years. Among all patients, CRT improved OS (HR=0.81, 95% CI: 0.68-0.97, P=0.026). Although CRT improved OS in the subgroup with ENE and/or positive margins (HR=0.71, 95% CI: 0.57-0.89, P=0.003) and not in those without these features (HR=0.94, 95% CI: 0.68-1.30, P=0.7), tests of interaction showed no evidence of a differential effect of CRT in these subgroups (P-interaction=0.17). There was also no evidence of interaction when analyzing other outcomes, or when assessing ENE and margin status individually. While CRT significantly reduced CSM (HR=0.68, 95% CI: 0.55-0.83, P<0.001), it also significantly increased OCM (HR=1.51, 95% CI: 1.07-2.12, P =0.018). PO-CRT improved locoregional recurrence (HR=0.64, 95% CI: 0.48-0.85, P=0.002), but not distant metastasis (HR=0.83, 95% CI=0.64-1.08, P=0.17).</p><p><strong>Conclusions: </strong>Concurrent chemotherapy improved OS in HNC patients undergoing post-operative radiotherapy in the combined populations of EORTC 22931 and RTOG 9501. ENE and/or positive margins are not predictive biomarkers, and patients without these features may still benefit from CRT. CRT improved CSM, but this was partly offset by higher OCM. Refining the population most likely to benefit from post-operative CRT, taking into consideration both oncologic and patient-related factors, needs further exploration.</p><p><strong>Trial registration: </strong>NRG Oncology's RTOG 9501 (https://clinicaltrials.gov/study/NCT00002670) and EORTC 22931 (https://clinicaltrials.gov/study/NCT00002555).</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666843","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 next-generation of nectin-4 targeted therapies","authors":"C. Pobel ,&nbsp;Y. Loriot","doi":"10.1016/j.annonc.2025.06.002","DOIUrl":"10.1016/j.annonc.2025.06.002","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 8","pages":"Pages 849-850"},"PeriodicalIF":56.7,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623808","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":"Reply to the Letter to the Editor by Szarpak et al.","authors":"I A van Assche, E Huis In 't Veld, K van Calsteren, J Lemiere, T Salaets, M M van den Heuvel-Eibrink, F Amant","doi":"10.1016/j.annonc.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.06.011","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615952","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":"Editorial to: \"Long-term development of 12- and 15-year-old offspring after maternal cancer diagnosis during pregnancy: a prospective multicentre cohort study\" by E. A. Huis in 't Veld et al. Cancer During Pregnancy - a childbearing potential.","authors":"S Loibl, B Winter, M Reinisch","doi":"10.1016/j.annonc.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.07.001","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607215","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":"Re: Long-term follow-up of PAOLA-1 and the evolving landscape of post-PARP treatment strategies in ovarian cancer.","authors":"Martina Parenza Arenhardt, Angélica Nogueira-Rodrigues","doi":"10.1016/j.annonc.2025.06.016","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.06.016","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599185","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":"Neoadjuvant Intralesional Targeted Immunocytokines (Daromun) in Stage III Melanoma.","authors":"K C Kähler, J C Hassel, M Ziemer, P Rutkowski, F Meier, L Flatz, C Gaudy-Marqueste, L Zimmer, M Santinami, F Russano, I von Wasielewski, T K Eigentler, M Maio, I Zalaudek, S Haferkamp, P Quaglino, J Welzel, C Röcken, A Enk, J-C Simon, T Świtaj, M Garzarolli, T Amaral, N Malissen, E Livingstone, G Elia, A Covelli, K Lorizzo, D Neri, S Mulatto, A Parca, B Pizzichi, P A Ascierto, C Garbe, C Robert, D Schadendorf, A Hauschild","doi":"10.1016/j.annonc.2025.06.014","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.06.014","url":null,"abstract":"<p><strong>Background: </strong>This phase 3 trial assessed daromun, a combination of two fibronectin-targeting immunocytokines (L19IL2 and L19TNF), as a neoadjuvant treatment for patients with clinically detectable stage IIIB/C melanoma (AJCC version 7).</p><p><strong>Methods: </strong>Patients were randomized to 4 weekly intralesional daromun administrations (13 Mio IU of L19IL2 and 400 μg of L19TNF) followed by surgery, or upfront surgery. Pretreatment with approved adjuvant agents was allowed. The primary endpoint was recurrence-free survival (RFS): events were disease recurrence or death from any cause after complete surgical tumor resection.</p><p><strong>Key findings: </strong>246 patients were randomized and included in the intention-to-treat analysis: 74% had undergone ≥ 2 prior surgical resections and 35% had received prior systemic therapy. At a median follow-up of 21 months, the neoadjuvant group (N=122) had a significantly longer RFS than the upfront surgery group (N=124), with a median RFS of 16.7 and 6.8 months, respectively (HR 0.59; 95% CI 0.41 to 0.86, p=0.005, log-rank test). The risk of distant recurrence was reduced by 40% in the neoadjuvant arm (HR=0.60; 95% CI [0.37; 0.95]; p=0.029). Grade ≥ 3 treatment-related adverse events (TRAEs) were 6.7% in the surgery alone arm and 27.1% in the daromun arm, mostly injection site reactions.</p><p><strong>Conclusions: </strong>Neoadjuvant daromun resulted in a significantly longer RFS than upfront surgery in patients with locally advanced melanoma. TRAEs were transient and manageable. Neoadjuvant daromun is a new therapeutic option for patients with stage III melanoma, including those with locoregional recurrence after surgery and previous adjuvant therapy.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599184","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":"Comparative genomic landscape of acquired resistance in pancreatic cancer treated with pan-RAS or KRAS^G12C inhibitors.","authors":"Florian Castet, Tian V Tian, Teresa Macarulla","doi":"10.1016/j.annonc.2025.06.018","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.06.018","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582892","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":"Prognostic significance of early on-treatment evolution of circulating tumor DNA in advanced ER+/HER2- breast cancer.","authors":"A Mamann, Y Pradat, F C Bidard, S Delaloge, L Cabel, I Faull, S Marques, T Bachelot, F Dalenc, T DE LA Motte Rouge, B Pistilli, J Samaniego, J S Frenel, C Levy, J M Ferrero, R Sabatier, S Ladoire, C Chakiba, A C Hardy, J Lemonnier, Y Mahi, F Andre, P H Cournede, S Michiels, E Bernard","doi":"10.1016/j.annonc.2025.06.015","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.06.015","url":null,"abstract":"<p><strong>Background: </strong>Patients with advanced estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer commonly develop resistance to treatment with hormone therapy and cyclin-dependent kinases 4/6 (CDK4/6) inhibitors. Responders cannot be distinguished from non-responders after the first cycle of treatment under current practice. We assessed circulating tumor DNA (ctDNA) measures at early time-points as prognostic markers.</p><p><strong>Patients and methods: </strong>Paired plasma samples were collected at baseline and early on-treatment (median 28 days) from 369 patients with advanced ER+/HER2- breast cancer treated in the PADA-1 trial with hormone therapy and a CDK4/6 inhibitor. Cell-free DNA was profiled with a 497-gene panel (Guardant360 LDT).</p><p><strong>Results: </strong>Baseline ctDNA levels including the mean variant allele frequency (VAF) (progression-free survival [PFS] HR = 1.07 [1.05, 1.09] P<0.001, overall survival [OS] HR = 1.08 [1.05, 1.11] P<0.001) and the number of driver somatic mutations (PFS HR = 1.13 [1.07, 1.19], P<0.001 and OS HR = 1.16 [1.07, 1.24], P<0.001) were prognostic. Early on-treatment ctDNA dynamics were also associated with outcomes, including the number of driver somatic mutations with VAF>0.5% at both timepoints (PFS HR = 1.39 [1.27,1.53] P<0.001 and OS HR = 1.51 [1.35,1.68] P<0.001) and the number of driver somatic mutations with a VAF increase (PFS HR = 1.31 [1.19,1.44] P<0.001 and OS HR = 1.10 [1.02,1.18] P=0.02). A ctDNA-based risk model incorporating baseline and dynamic ctDNA features was independently prognostic from RECIST in multivariable models (Test set: OS HR = 4.10 [1.93,8.72], P<0.001, PFS HR = 1.86 [1.16,2.97], P=0.009). The integration of ctDNA features into a clinical model improved survival discrimination for PFS (C-index 64.7% [s.d. 2.5] for a ctDNA & clinical model vs. 59.3% [s.d. 2.2] for a clinical only model, p=0.027) and for OS (C-index 70.0% [s.d 3.4] vs. 60.3% [s.d. 4.2], p=0.035).</p><p><strong>Conclusions: </strong>Early on-treatment evolution of ctDNA is prognostic for both PFS and OS in advanced ER+/HER2- breast cancer. A ctDNA-based risk model improves upon traditional RECIST and clinical parameters, advocating for ctDNA as a prognostic biomarker in clinical practice.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582893","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}