Annals of Oncology最新文献

{"title":"Redefining Clinical Trial Strategic Design to Support Drug Approval in Medical Oncology.","authors":"G Antonarelli, J M Pérez-García, M Gion, H Rugo, P Schmid, A Bardia, S Hurvitz, N Harbeck, S M Tolaney, G Curigliano, A Llombart-Cussac, J Cortés","doi":"10.1016/j.annonc.2025.03.005","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.005","url":null,"abstract":"<p><p>Randomized clinical trials represent the gold standard for the introduction of innovative therapies in medical oncology, and they provide the highest level of evidence to ascertain the clinical activity of new drugs or novel combinations. However, the current infrastructure of clinical trials supporting innovative drug approvals is challenged by an increased body of knowledge concerning tumor biology and therapy resistance, a fast-growing armamentarium of novel anti-cancer compounds, an impressively upscaled data analysis capacity, as well as increasing costs related to clinical trials' management. In this scenario, modern clinical trial designs need to evolve to expedite new drug approvals by tailoring patients' treatment strategies according to their medical needs. Balanced, patient-oriented, clinical trial designs are eagerly warranted to increase their efficiency, to include the fast-pace of technological innovations and scientific discoveries, and ultimately to face the challenges of the modern medical oncology field.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630049","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":"Advanced cancer: a robust surrogate of cancer mortality in early detection trials?","authors":"P Sasieni, C Swanton, R Neal","doi":"10.1016/j.annonc.2025.03.001","DOIUrl":"10.1016/j.annonc.2025.03.001","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613163","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":"Oncologic outcomes of retroperitoneal lymph node dissection following first-line chemotherapy for metastatic non-seminomatous germ-cell tumors.","authors":"R S Matulewicz, F Baky, N Liso, B M Williams, S Porwal, M Assel, B S Carver, D F Bajorin, R J Motzer, G J Bosl, D J McHugh, V E Reuter, S K Tickoo, H Al-Ahmadie, A J Vickers, S A Funt, D R Feldman, J Sheinfeld","doi":"10.1016/j.annonc.2025.03.002","DOIUrl":"10.1016/j.annonc.2025.03.002","url":null,"abstract":"<p><strong>Background: </strong>Post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) is integral to multimodal treatment of patients with metastatic non-seminomatous germ-cell tumors (NSGCT). We review pathologic and long-term outcomes of pcRPLND following first-line chemotherapy with a focus on residual mass size and primary tumor histology. Our goal was to identify new predictive approaches that can refine surgical indications.</p><p><strong>Patients and methods: </strong>Patients who underwent pcRPLND for NSGCT at our institution between 1 January 2000 and 18 January 2023 following first-line chemotherapy were included. The primary outcome was surgical pathology categorized as (i) viable non-teratomatous germ-cell tumor (GCT) (with or without teratoma), (ii) teratoma only, or (iii) fibrosis/necrosis stratified by largest residual mass size. Secondary outcomes included 10-year relapse-free survival, disease-specific survival, and overall survival.</p><p><strong>Results: </strong>Of 1027 eligible patients, 45% had teratoma and 4% had viable non-teratomatous GCT found at pcRPLND. With a median follow-up of 5.2 years, there was one isolated retroperitoneal relapse and 26 GCT-related deaths. As the residual mass size increased, the likelihood of teratoma in the pcRPLND specimen increased from ∼20% (residual masses <1 cm) to ∼70% (>5 cm). The risk of viable non-teratomatous GCT similarly increased from ∼2% up to ∼10%. Ten-year relapse-free and overall survival worsened with increasing mass size. Adjusting for risk group, clinical stage, residual mass size, and lymphovascular invasion at orchiectomy, the presence of yolk sac tumor [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.35-2.56] and teratoma in the orchiectomy specimen (OR 3.09, 95% CI 2.27-4.23) were each independently associated with finding teratoma or viable non-teratomatous GCT at pcRPLND.</p><p><strong>Conclusions: </strong>Following first-line chemotherapy, pcRPLND provides effective control of the retroperitoneum with few relapses and GCT-related deaths. Guideline recommendations for or against pcRPLND based on residual mass size alone should be revisited due to the significant association of orchiectomy histology with pcRPLND pathology and the benefits surgical consolidation has on disease control and survival.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613170","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":"Efficacy assessment in phase I clinical trials: endpoints and challenges.","authors":"M A Gouda, P A Ballesteros, I Garrido-Laguna, J Rodon","doi":"10.1016/j.annonc.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.02.010","url":null,"abstract":"<p><p>The scope of phase I clinical trials in oncology goes beyond the conventional safety evaluation-only objectives of these trials in other specialties. Rather, most first-in-human cancer trials have therapeutic intent, and efficacy signals observed in phase I trials can drive a go/no-go decision of advancing a new molecule to phase II testing. The complexity of efficacy assessment in the context of a small, heterogenous patient population and a complex study design requires a more liberal perspective compared to later trial phases when looking into efficacy endpoints. Classically, in later phase clinical trials, these endpoints would include the objective response rate, progression-free survival, and overall survival. However, new, evolving endpoints may be worth investigating when looking into the antitumor activity signals in phase I trials. Integration of all these endpoints into trial designs can improve the assessment of therapeutic efficacy during early drug development and guide decisions related to further advancement of novel molecules into later phases. In this review, we discuss the advantages and pitfalls of different classic efficacy endpoints when evaluated as part of phase I trials in oncology and describe how challenges in assessing the antitumor activity of new drugs can be overcome through incorporation of novel endpoints that have thus far proven successful in clinical trials.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571688","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":"Efficacy and safety of neoadjuvant SHR-A1811 with or without pyrotinib in women with locally advanced or early HER2-positive breast cancer: a randomized, open-label, phase II trial.","authors":"J Li, Z H Wang, L Chen, W J Zhang, L X X Ma, J Wu, G Y Liu, Y F Hou, K D Yu, G H Di, L Fan, Y Z Jiang, S H Jiang, Q N Liang, Y Shen, Z-M Shao","doi":"10.1016/j.annonc.2025.02.011","DOIUrl":"10.1016/j.annonc.2025.02.011","url":null,"abstract":"<p><strong>Background: </strong>Standard neoadjuvant regimens for human epidermal growth factor receptor 2 (HER2)-positive breast cancer include trastuzumab and pertuzumab combined with chemotherapy, and the efficacy and safety of third-generation HER2-directed antibody-drug conjugate (ADC) remain to be elucidated.</p><p><strong>Patients and methods: </strong>This open-label, randomized, phase II study enrolled patients aged ≥18 years with stage II-III HER2-positive breast cancer. Patients were randomly assigned (1 : 1 : 1) to receive neoadjuvant treatment either with SHR-A1811 monotherapy, SHR-A1811 with pyrotinib, or nab-paclitaxel combined with carboplatin, trastuzumab, and pertuzumab (PCbHP) for 24 weeks. The primary endpoint was pathological complete response (pCR). Safety was analysed in patients who received at least one dose of study medication.</p><p><strong>Results: </strong>Between 27 December 2022 and 11 February 2024, 265 patients were randomly allocated to neoadjuvant, mono-SHR-A1811 (n = 87), SHR-A1811 plus pyrotinib (n = 88), or PCbHP (n = 90). The baseline characteristics were well balanced; ∼45% of the patients were hormone receptor (HR) positive, and 70% of the patients were stage III. The pCR rate was 63.2% for mono-SHR-A1811 (50% for HR positive and 74.5% for HR negative), 62.5% for SHR-A1811 plus pyrotinib (44.7% for HR positive and 76% for HR negative), and 64.4% for PCbHP (54.1% for HR positive and 71.7% for HR negative), with no significant difference between the groups. Grade ≥3 treatment-related adverse events occurred in 44.8% of patients with mono-SHR-A1811, 71.6% with SHR-A1811 plus pyrotinib, and 38.8% with PCbHP. One patient experienced grade 2 interstitial lung disease in SHR-A1811, 9.1% of patients experienced grade 3 diarrhoea in SHR-A1811 plus pyrotinib, and no treatment-related deaths occurred.</p><p><strong>Conclusions: </strong>This is the first study to report the efficacy and safety of third-generation HER2-directed ADC in the neoadjuvant setting for HER2-positive breast cancer. SHR-A1811 showed robust activity, with a tolerable safety profile.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571677","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 Letter to the Editor: 'A phase III randomised trial on the addition of a contact x-ray brachytherapy boost to standard neoadjuvant chemo-radiotherapy for organ preservation in early rectal adenocarcinoma: 5 years results of the OPERA trial' by J. Meyer, T. Koessler.","authors":"D Baron, S Ben Dhia, J-P Gerard, J Doyen","doi":"10.1016/j.annonc.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.02.003","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555569","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":"Enhancing radiotherapy with PARP inhibition in soft-tissue sarcomas: a promising synergy requiring specific attention to normal tissues?","authors":"A Levy, C Clémenson, M Mondini, C Ngo, B Verret, M Faron, A Le Cesne, C Quevrin, S Besseri, S Reichl, Y Ghannam, A Camps-Malea, D Lavigne, C Le Péchoux, E Deutsch","doi":"10.1016/j.annonc.2025.02.007","DOIUrl":"10.1016/j.annonc.2025.02.007","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514427","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":"Corrigendum to “Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group”","authors":"M.F. Mosele ,&nbsp;C.B. Westphalen ,&nbsp;A. Stenzinger ,&nbsp;F. Barlesi ,&nbsp;A. Bayle ,&nbsp;I. Bièche ,&nbsp;J. Bonastre ,&nbsp;E. Castro ,&nbsp;R. Dienstmann ,&nbsp;A. Krämer ,&nbsp;A.M. Czarnecka ,&nbsp;F. Meric-Bernstam ,&nbsp;S. Michiels ,&nbsp;R. Miller ,&nbsp;N. Normanno ,&nbsp;J. Reis-Filho ,&nbsp;J. Remon ,&nbsp;M. Robson ,&nbsp;E. Rouleau ,&nbsp;A. Scarpa ,&nbsp;F. André","doi":"10.1016/j.annonc.2024.11.010","DOIUrl":"10.1016/j.annonc.2024.11.010","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Page 472"},"PeriodicalIF":56.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472067","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}

{"title":"Corrigendum to “582P Knowledge, attitude and practices of physicians in Pakistan towards onco-hypertension”","authors":"M. Hashmi ,&nbsp;S.S. Yaqub ,&nbsp;U.A. Rahman ,&nbsp;E.S.A. Alfadul ,&nbsp;H.S. Jabeen ,&nbsp;M.N.S. Saddique ,&nbsp;K.J. Javaid ,&nbsp;M.S. Siddique ,&nbsp;M.A. Khokhar","doi":"10.1016/j.annonc.2024.12.012","DOIUrl":"10.1016/j.annonc.2024.12.012","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Page 473"},"PeriodicalIF":56.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679124","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}

{"title":"Hepatocellular carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.","authors":"A Vogel, S L Chan, L A Dawson, R K Kelley, J M Llovet, T Meyer, J Ricke, L Rimassa, G Sapisochin, V Vilgrain, J Zucman-Rossi, M Ducreux","doi":"10.1016/j.annonc.2025.02.006","DOIUrl":"10.1016/j.annonc.2025.02.006","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476225","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}