Annals of Oncology最新文献

{"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 2 trial.","authors":"J 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":"https://doi.org/10.1016/j.annonc.2025.02.011","url":null,"abstract":"<p><strong>Background: </strong>Standard neoadjuvant regimens for HER2-positive breast cancer include trastuzumab and pertuzumab combined with chemotherapy, and the efficacy and safety of third-generation HER2-direted antibody-drug conjugate (ADC) remain to be elucidated.</p><p><strong>Patients and methods: </strong>This open-label, randomized, phase 2 study enrolled patients aged 18 years or older 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 December 27, 2022, and February 11, 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; approximately 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+ and 74.5% for HR-), 62.5% for SHR-A1811 plus pyrotinib (44.7% for HR+ and 76% for HR-) and 64.4% for PCbHP (54.1% for HR+ and 71.7% for HR-), with no significant difference between the groups. Grade 3 or higher 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 diarrhea 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. (ClinicalTrials.gov, NCT05582499).</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 Radiation Therapy 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":"https://doi.org/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\": [Ann Oncol 35 (2024) 588-606].","authors":"M F Mosele, C B Westphalen, A Stenzinger, F Barlesi, A Bayle, I Bièche, J Bonastre, E Castro, R Dienstmann, A Krämer, A M Czarnecka, F Meric-Bernstam, S Michiels, R Miller, N Normanno, J Reis-Filho, J Remon, M Robson, E Rouleau, A Scarpa, C Serrano, J Mateo, F André","doi":"10.1016/j.annonc.2024.11.010","DOIUrl":"https://doi.org/10.1016/j.annonc.2024.11.010","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":"143472067","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":"Unravelling lung adenocarcinoma with mucinous histology and its translational implications","authors":"S.S. Prince ,&nbsp;O. Chijioke ,&nbsp;L. Bubendorf","doi":"10.1016/j.annonc.2025.01.007","DOIUrl":"10.1016/j.annonc.2025.01.007","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 3","pages":"Pages 235-237"},"PeriodicalIF":56.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444453","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":"Locally advanced microsatellite instability-high esophagogastric cancer: are we ready to change our treatment paradigm?","authors":"D.H. Ilson","doi":"10.1016/j.annonc.2025.01.010","DOIUrl":"10.1016/j.annonc.2025.01.010","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 3","pages":"Pages 233-234"},"PeriodicalIF":56.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444417","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":"Targeting the future: Antibody-Drug Conjugates (ADCs) in platinum-sensitive ovarian cancer in the post-PARP era","authors":"L.M. Chambers ,&nbsp;R.N. Eskander ,&nbsp;D.M. O’Malley","doi":"10.1016/j.annonc.2025.01.015","DOIUrl":"10.1016/j.annonc.2025.01.015","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 3","pages":"Pages 244-246"},"PeriodicalIF":56.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444418","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":"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":"https://doi.org/10.1016/j.annonc.2025.02.006","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-02-19","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}

{"title":"Anti-PD-1 treatment for MSI-H/MMRD tumors. A journey from genomics to transformative patient breakthroughs","authors":"G. Argilés ,&nbsp;D. Arnold ,&nbsp;A. Cervantes","doi":"10.1016/j.annonc.2025.01.018","DOIUrl":"10.1016/j.annonc.2025.01.018","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 3","pages":"Pages 231-232"},"PeriodicalIF":56.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445218","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}