Avelumab

点击蓝字，关注我们 三阴性乳腺癌的雌激素受体、孕激素受体和人类表皮生长因子受体HER2均为阴性，对传统的内分泌治疗和HER2靶向治疗无效，早期患者主要依靠手术和化疗。近年来，免疫检查点抑制剂已被证实对于晚期三阴性乳腺癌有效。免疫检查点是人体平衡免疫功能的两类分子，一类负责激活免疫细胞，另一类负责抑制免疫细胞，后者包括免疫细胞程序性死亡受体PD-1及其配体PD-L1，肿瘤细胞能够利用PD-1和PD-L1让免疫细胞进入自杀程序，避免自己被免疫细胞消灭，而PD-1或PD-L1抑制剂可以恢复免疫细胞抗肿瘤功能。不过，对于高风险早期三阴性乳腺癌，目前仅KEYNOTE-522研究证实PD-1抑制剂帕博利珠单抗术前新辅助治疗＋术后辅助治疗有效，可显著改善患者的病理完全缓解率、无事件生存和总生存，其他PD-1或PD-L1抑制剂已告失败。 2025年8月28日，欧洲肿瘤内科学会官方期刊《肿瘤学年鉴》在线发表意大利帕多瓦大学设计并发起的A-BRAVE研究报告，首次对PD-L1抑制剂阿维利尤单抗辅助治疗高风险早期三阴性乳腺癌术后患者的有效性和安全性进行随机比较。 A-BRAVE (NCT02926196): Adjuvant Treatment for High-risk Triple Negative Breast Cancer Patients With the Anti-PD-l1 Antibody Avelumab 该国际多中心非盲随机对照三期临床研究于2016年6月至2020年10月从60家意大利医院和7家英国医院入组高风险早期三阴性乳腺癌完成手术和化疗等标准治疗患者466例，按1比1随机分为两组，其中235例每2周静脉输注阿维利尤单抗治疗1年，其余231例观察。高风险分为两类：Ａ类83例（18%）初次手术后任何pT且≥pN2、pT2且pN1、pT3且pN0，Ｂ类383例（82%）术前化疗后乳腺和/或淋巴结残留浸润癌。主要终点包括全部患者和Ｂ类患者的无癌生存，次要终点包括全部患者的总生存和PD-L1测定患者的无癌生存，事后探索性分析终点包括全部患者的远处无癌生存。通过免疫组织化学和数字病理学对治疗前肿瘤样本PD-L1进行测定。若主要终点有统计学显著差异，则对次要终点进行统计学分析，否则仅进行描述性分析。 结果，中位随访52.1个月，阿维利尤单抗组与观察组相比： 全部患者3年无癌生存率相似：68.3%比63.2%（风险比：0.81，95%置信区间：0.61～1.09，P=0.172） Ｂ类患者3年无癌生存率相似：66.9%比60.7%（风险比：0.80，95%置信区间：0.58～1.10，P=0.170） 全部患者3年总生存率较高：84.8%比76.3%（风险比：0.66，95%置信区间：0.45～0.97） 全部患者3年远处无癌生存较高：75.4%比67.9%（风险比：0.70，95%置信区间：0.50～0.96） PD-L1阳性与阴性相比，患者3年无癌生存率较高：80.9%比64.2%（风险比：0.45，95%置信区间：0.26～0.78，P=0.003）。 不过，阿维利尤单抗组与观察组相比： PD-L1阳性患者3年无癌生存率相似：67.5%比60.7%（风险比：1.72（95%置信区间：0.58～5.12） PD-L1阴性患者3年无癌生存率相似：84.8%比77.1%（风险比：0.76（95%置信区间：0.54～1.08） PD-L1不能预测阿维利尤单抗无癌生存获益（相互作用检验P=0.155） 因此，该小规模研究短期随访结果表明，对于早期三阴性乳腺癌复发风险较高患者，完成手术和化疗等标准治疗后，阿维利尤单抗辅助治疗1年与观察相比，3年无癌生存并未改善。不过，出乎意料的是，描述性和探索性分析表明，阿维利尤单抗对3年总生存和远处无癌生存产生有利影响，可能减少远处转移和死亡风险，故有必要进一步长期随访并开展大规模研究进行验证，才能确定其对临床实践的潜在影响。PD-L1虽然可以预测患者无癌生存，但是不能预测阿维利尤单抗无癌生存获益。 相关链接 不可思议的乳腺癌患者总生存曲线 Ann Oncol. 2025 Aug 28. IF: 65.4 A-BRAVE trial: a Phase 3 randomized trial with anti-PD-L1 avelumab in high-risk triple-negative early breast cancer patients. Conte PF, Dieci MV, Bisagni G, Schmid P, Zambelli A, Piacentini F, De Laurentiis M, Favaretto AG, Tamberi S, Bianchi GV, Zamagni C, Cinieri S, Corsi DC, Del Mastro L, Ferro A, Gennari A, Mion M, Musolino A, Nicolé L, Del Bianco P, De Salvo GL, Guarneri V. University of Padova, Padova, Italy; Veneto Institute of Oncology IOV IRCCS, Padova, Italy; Azienda USL-IRCCS, Reggio Emilia, Italy; ASST Papa Giovanni XXIII, Bergamo, Italy; Bicocca University, Milan, Italy; University Hospital of Modena, Modena, Italy; Azienda Ospedaliero-Universitaria di Modena, Modena, Italy; Istituto Nazionale Tumori Napoli IRCCS "Fondazione Pascale", Napoli, Italy; Azienda ULSS 2 Marca Trevigiana, Treviso, Italy; Santa Maria delle Croci hospital, Ravenna, Italy; Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Perrino Hospital, ASL Brindisi, Brindisi, Italy; Ospedale Isola Tiberina, Gemelli Isola Rome, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy; Università degli Studi di Genova, Genova, Italy; Santa Chiara Hospital, Trento, Italy; Università del Piemonte Orientale, Novara, Italy; AULSS6 Camposampiero, Camposampiero, Italy; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy; University of Bologna, Bologna, Italy; Angelo Hospital, Mestre, Italy; Queen Mary University of London, London, United Kingdom. HIGHLIGHTS A-BRAVE is a Phase III study of 1-year avelumab versus observation after standard treatment in high-risk TNBC. Avelumab as adjuvant therapy versus observation did not improve DFS in high-risk early TNBC patients OS analysis suggests a potential favorable impact of avelumab versus observation. PD-L1 status was not predictive for avelumab efficacy. BACKGROUND: The A-BRAVE trial evaluated the efficacy of avelumab, an anti PD-L1 antibody, as adjuvant treatment for patients with early triple-negative breast cancer (TNBC) at high-risk. PATIENTS AND METHODS: A-BRAVE is a Phase III study that randomized patients with high-risk early TNBC to 1-year avelumab vs observation, after completion of standard surgery and neoadjuvant/adjuvant chemotherapyHigh-risk was defined as either: 1) >pN2/any pT, pN1/pT2, or pN0/pT3 after primary surgery (Stratum A); or 2) invasive residual disease (breast and/or nodes) after neoadjuvant chemotherapy (Stratum B). Co-primary endpoints were disease-free survival (DFS) in the intention-to-treat (ITT) and Stratum B populations (). Secondary endpoints were overall survival (OS) and DFS in PD-L1-positive patients. PD-L1 was evaluated in treatment-naive tumor samples by immunohistochemistry (73-10 RUO assay, Agilent Technologies) and digital pathology. RESULTS: From June 2016 to October 2020, 466 patients were randomized: 383 entered Stratum B (82%) and 83 entered Stratum A (18%). At a median follow of 52.1 months, avelumab did not significantly improve DFS in the ITT population (HR 0.81, 95% CI 0.61-1.09, p=0.172; 3-year DFS estimates were 68.3% for avelumab versus 63.2%), or in Stratum B (HR 0.80, 95% CI 0.58-1.10, p=0.170; 3-year DFS estimates were 66.9% for avelumab versus 60.7%). In a descriptive analysis, avelumab reduced the hazard of OS events: HR 0.66, 95% CI: 0.45-0.97. The 3-year OS estimates for avelumab and control arm were 84.8% (95% CI: 79.5-88.8) and 76.3% (95% CI: 70.1-81.3), respectively. PD-L1 status resulted prognostic but not predictive for avelumab benefit in terms of DFS (test for interaction p=0.155). CONCLUSIONS: For patients with TNBC at high risk of relapse who complete standard treatment with surgery and neoadjuvant/adjuvant chemotherapy, 1 year of adjuvant avelumab versus observation did not improve DFS. However, a descriptive analysis suggests a potential favorable impact on OS. ClinicalTrials.gov identifier: NCT02926196 KEYWORDS: Breast cancer, clinical trial, immunotherapy, triple-negative breast cancer, PD-L1 DOI: 10.1016/j.annonc.2025.08.005 （来源：SIBCS） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Ajovy (fremanezumab-vfrm) Emgality (galcanezumab-gnlm) Nurtec ODT (rimegepant) Ubrelvy (ubrogepant) Vyepti (eptinezumab-jjmr) Hypertension The "Warnings and Precautions", "Adverse Reactions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in March 2025 to include information about the risk of hypertension. Example: Ajovy labeling Apriso (mesalamine) Asacol (mesalamine) Asacol HD (mesalamine) Azulfidine (sulfasalazine) Azulfidine EN-Tabs (sulfasalazine) Canasa (mesalamine) Colazal (balsalazide disodium) Delzicol (mesalamine) Dipentum (osalazine sodium) Giazo (balsalazide disodium) Lialda (mesalamine) Rowasa (mesalamine) Pentasa (mesalamine) Severe cutaneous adverse reactions The Warnings and Precautions section of the labeling was updated November 2021 to include severe cutaneous adverse reactions. Example: Delzicol labeling Avastin (bevacizumab) Mvasi (bevacizumab-awwb) Zirabev (bevacizumab-bvzr) Pancreatitis FDA determined that no action is necessary at the time based on available information. Avastin (bevacizumab) Mvasi (bevacizumab-awwb) Zirabev (bevacizumab-bvzr) Anaphylactic shock The "Warnings and Precautions" section of the labeling was updated between September 2022 and February 2023 to include anaphylactoid/anaphylactic reactions. Example: Avastin labeling Ayvakit (avapritinib) Photosensitivity reaction The "Warnings and Precautions", "Adverse Reactions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in March 2023 to include information about photosensitivity. Ayvakit labeling Azacitidine Onureg (azacitidine) Vidaza (azacitidine) Generic products containing azacitidine Pericarditis The "Adverse Reactions" section of the labeling was updated between September 2022 and June 2023 to include pericarditis. Example: Vidaza labeling FDA determined that no action is necessary at the time based on available information for Onureg. Bavencio (avelumab) Imfinzi (durvalumab) Libtayo (cemiplimab-rwlc) Keytruda (pembrolizumab) Opdivo (nivolumab) Tecentriq (atezolizumab) Yervoy (ipilimumab) Tumour lysis syndrome FDA determined that no action is necessary at the time based on available information. Cymbalta (duloxetine hydrochloride) Drizalma Sprinkle (duloxetine hydrochloride) Generic products containing duloxetine hydrochloride Anosmia, Hyposmia This issue is posted as two individual newly identified safety signal (NISS) entries in the January-March 2022 quarter, to reflect the focus on the potential signals of anosmia and hyposmia, separately. Darzalex (daratumumab) Darzalex Faspro (daratumumab and hyaluronidase-fihj) Blood stem cell transplant failure FDA determined that no action is necessary at the time based on available information. Dipeptidyl peptidase-4 (DPP-4) inhibitors Glyxambi (empagliflozin and linagliptin) Janumet (metformin hydrochloride and sitagliptin phosphate) Janumet XR (metformin hydrochloride and sitagliptin phosphate) Jentadueto (linagliptin and metformin hydrochloride) Jentadueto XR (linagliptin and metformin hydrochloride) Kazano (alogliptin and metformin hydrochloride) Kombiglyze XR (metformin hydrochloride and saxagliptin) Nesina (alogliptin) Onglyza (saxagliptin) Oseni (alogliptin and pioglitazone) Steglujan (ertugliflozin and sitagliptin) Tradjenta (linagliptin) Trijardy XR (empagliflozin, linagliptin and metformin hydrochloride) Qtern (saxagliptin and dapagliflozin) Generic products containing dipeptidyl peptidase-4 inhibitors Tubulointerstitial nephritis The "Adverse Reactions" section of the labeling was updated between March 2022 and June 2022 for products containing alogliptin and sitagliptin to include tubulointerstitial nephritis. Example: Janumet labeling FDA determined that no action is necessary for products containing linagliptin and saxagliptin at the time based on available information. *An administrative error resulted in the omission of Januvia from the list of product names after the initial quarterly report was posted. Dupixent (dupilumab) Angioedema The "Warnings and Precautions" and "Adverse Reactions" sections of the labeling were updated in December 2021 to include angioedema. Dupixent labeling Glucagon-like peptide-1 (GLP-1) analogues Adlyxin (lixisenatide) Bydureon (exenatide) Bydureon BCise (exenatide) Byetta (exenatide) Ozempic (semaglutide) Rybelsus (semaglutide) Saxenda (liraglutide) Soliqua 100/33 (insulin glargine and lixisenatide injection) Trulicity (dulaglutide) Victoza (liraglutide) Wegovy (semaglutide) Xultophy 100/3.6 (insulin degludec and liraglutide injection) Generic products containing glucagon-like peptide-1 analogues Gallbladder related disorders The "Warnings and Precautions", "Adverse Reactions", and "Patient Counseling Information" sections of the GLP-1 analogues labeling were updated between March 2022 and June 2022 to include information about acute gallbladder disease. Example: Adlyxin labeling FDA has determined that the last approved labeling for Saxenda and Wegovy is adequately labeled for acute gallbladder disease, and that no further regulatory action is needed at this time. Gonadotropin releasing hormone (GnRH) analogues Fensolvi (leuprolide acetate) Lupron Depot-PED (leuprolide acetate) Supprelin LA (histrelin acetate) Synarel (nafarelin acetate) Triptodur (triptorelin) Idiopathic intracranial hypertension The "Warnings", "Precautions", and "Adverse Reactions" sections of the labeling were updated in April 2022 to include idiopathic intracranial hypertension. Example: Fensolvi labeling Jakafi (ruxolitinib phosphate) Herpes simplex virus (HSV) reactivation and/or disseminated HSV The "Dosage and Administration", "Warnings and Precautions", and "Adverse Reactions" sections of the labeling were updated in January 2023 to include information about herpes simplex and herpes zoster infections. Jakafi labeling Ibrance (palbociclib) Kisqali (ribociclib) Kisqali Femara Co-Pack (letrozole and ribociclib) Embolic and thrombotic events, venous The "Adverse Reactions" section of the Ibrance labeling was updated in December 2024 to include venous thromboembolism. Ibrance labeling FDA determined that no action is necessary at the time for Kisqali and Kisqali Femara Co-Pack based on available information. Ocrevus (ocrelizumab) Myocardial infarction FDA determined that no action is necessary at the time based on available information. Potassium Chloride Product preparation error The “Warnings” section of the labeling was updated in December 2022 to include information about fatal cardiac adverse reactions with intravenous administration of undiluted potassium chloride. Praxbind (idarucizumab) Wrong dose errors The carton labeling and "Dosage and Administration" sections of the labeling were revised in February 2022 to clarify the number of vials included in each carton and the recommended dosing. Praxbind labeling Qbrexza (glycopyrronium tosylate) Accidental exposure to product The container label, carton labeling, "Dosage and Administration", "Warnings and Precautions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in October 2022 to include information about accidental exposure. Qbrexza labeling Qbrexza (glycopyrronium tosylate) Urinary retention The “Warnings and Precautions”, “Adverse Reactions”, and “Patient Counseling Information” sections of the labeling were updated in October 2022 to include information about new or worsening urinary retention. Qbrexza labeling Sodium-glucose cotransporter-2 (SGLT-2) inhibitors Farxiga (dapagliflozin) Glyxambi (empagliflozin and linagliptin) Invokamet (canagliflozin and metformin hydrochloride) Invokamet XR (canagliflozin and metformin hydrochloride) Invokana (canagliflozin) Jardiance (empagliflozin) Qtern (saxagliptin and dapagliflozin) Steglatro (ertugliflozin) Steglujan (ertugliflozin and sitagliptin) Segluromet (ertugliflozin and metformin hydrochloride) Synjardy (empagliflozin and metformin hydrochloride) Synjardy XR (empagliflozin and metformin hydrochloride) Trijardy XR (empagliflozin, linagliptin and metformin hydrochloride) Xigduo XR (dapagliflozin and metformin) Generic products containing sodium-glucose cotransporter-2 (SGLT-2) inhibitors Tubulointerstitial nephritis FDA determined that no action is necessary at the time based on available information. Somatostatin Receptor Imaging Agents Detectnet (copper Cu-64 dotatate injection) Gallium Dotatoc (GA 68) Octreoscan (Indium In 111 Pentetreotide) Netspot (Gallium GA 68 Dotatate) Hypersensitivity The "Warnings and Precautions" and "Adverse Reactions" sections of the labeling were updated in December 2021 to include hypersensitivity reactions. Example: Netspot labeling Stromectol (ivermectin) Generic products containing ivermectin Off label use FDA determined that no action is necessary at the time based on available information. Stromectol (ivermectin) Generic products containing ivermectin Neurotoxicity The "Warnings", "Adverse Reactions", and "Overdosage" sections of the labeling were updated in March 2022 to include neurotoxicity. Example: Stromectol labeling Sunosi (solriamfetol hydrochloride) Hypersensitivity FDA determined that no action is necessary at the time based on available information. Vivitrol (naltrexone) Incorrect route of product administration The container label (vial), carton labeling, "Dosage and Administration", "Warnings and Precautions", and "Description", sections of the labeling were revised in September 2022 to emphasize the appropriate route and site of administration. Vivitrol labeling Xcopri (cenobamate) Psychiatric disorders The "Adverse Reactions" section of the labeling was updated in June 2022 to include psychiatric disorders. Xcopri labeling Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.