Paclitaxel

FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced positive topline results from the Phase 3 ASCENT-03 study of Trodelvy® (sacituzumab govitecan-hziy). The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy in patients with first-line metastatic triple-negative breast cancer (mTNBC) who are not candidates for PD-1/PD-L1 inhibitors, meaning they are PD-L1 negative or are ineligible to receive immunotherapy. “Almost half of the patients diagnosed with metastatic triple-negative breast cancer do not receive treatment beyond first-line, demonstrating an urgent need for innovative treatment options in this early setting,” said Dr. Javier Cortes, Head of the International Breast Cancer Center in Spain and principal investigator of the ASCENT-03 study. “Traditional chemotherapy has been the standard of care for early treatment of metastatic triple-negative breast cancer, and we know that therapeutic advances in this disease area serve a critical unmet need for patients and the broader oncology community.” Together with the recently announced positive results from the ASCENT-04 study evaluating Trodelvy plus Keytruda® in patients with previously untreated PD-L1+ metastatic TNBC, Trodelvy now has the potential to be the backbone treatment for all patients across first-line mTNBC. Detailed data from the ASCENT-04 study will be shared during the American Society of Clinical Oncology (ASCO) meeting taking place May 30 – June 3, 2025. “The ASCENT-03 outcome represents the first clinically meaningful advance for this patient population in over 20 years versus chemotherapy,” said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. “By addressing this aggressive and difficult to treat disease earlier, we can potentially improve treatment options for the high unmet need that patients with metastatic triple-negative breast cancer face.” The safety profile of Trodelvy in the ASCENT-03 study was consistent with prior studies, and no new safety signals were identified in this patient population. Overall survival (OS) is a key secondary endpoint and was not mature at the time of PFS primary analysis. No OS detriment was observed. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analysis planned. Detailed results from the ASCENT-03 study will be presented at a future medical meeting and discussed with regulatory authorities. The use of Trodelvy in first-line mTNBC is investigational, and the safety and efficacy of this use have not been established. Healthcare professionals have well-established experience with Trodelvy, which has shown generally consistent outcomes across both clinical trials and real-world studies in 60,000+ patients across 50+ countries over approximately five years. It is the only antibody-drug conjugate (ADC) with four positive Phase 3 trials in HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) metastatic breast cancer (mBC), and remains the only approved Trop-2-directed ADC that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers: 2L mTNBC and pre-treated HR+/HER2- mBC. Trodelvy is a Category 1 preferred treatment for both currently approved indications per the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelinesi) and the only ADC with an ESMO Magnitude of Clinical Benefit Scale (MCBS) rating of 5 for mTNBC. Trodelvy also has an MCBS rating of 4 for women with HR+/HER2- mBC. Currently, Gilead has additional ongoing Phase 3 studies investigating Trodelvy across HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer including the ASCENT-07 pivotal trial in patients with HR+/HER2- mBC who have received endocrine therapy, and the ASCENT-05 pivotal trial in patients with early-stage TNBC (eTNBC). Trodelvy is also being evaluated in additional Phase 3 studies across a range of tumor types, including in lung and gynecologic cancers. Gilead would like to thank the patients, families, investigators and advocates who have contributed and continue to contribute to this important research. We remain committed to advancing care to address the unmet needs for the breast cancer community. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About Triple-Negative Breast Cancer (In Patients Who Are Not Candidates for PD-1/PD-L1 inhibitors) Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC disproportionately impacts younger, pre-menopausal as well as Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of mBC. Chemotherapy remains the mainstay of treatment in first-line mTNBC patients who are not candidates for PD-1/PD-L1 inhibitors, and the need to improve outcomes continues to be high. In mTNBC overall, ~50% of patients do not receive treatment beyond 1L setting, demonstrating a need for additional effective earlier-line treatment options. About the ASCENT-03 Study The ASCENT-03 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of sacituzumab govitecan compared with treatment of physician’s choice in patients with previously untreated, locally advanced, inoperable, or metastatic triple-negative breast cancer (mTNBC) whose tumors do not express PD-L1, or who are PD-L1 positive and previously treated with a PD-(L)1 inhibitor in the curative setting. ~540 patients were enrolled across multiple study sites worldwide. Patients were randomized 1:1 to receive either sacituzumab govitecan (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) or treatment of physician’s choice, which included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. Patients randomized to chemotherapy were eligible to crossover to sacituzumab govitecan upon disease progression. The primary endpoint of the study is progression-free survival (PFS) as assessed by BICR according to RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs), and safety. More information about ASCENT-03 is available at ClinicalTrials.gov: NCT05382299. About Trodelvy Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect. Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer. Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer—including in curative settings—as well as in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity. INDICATIONS TRODELVY® (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. IMPORTANT SAFETY INFORMATION BOXED WARNING: NEUTROPENIA AND DIARRHEA CONTRAINDICATIONS Severe hypersensitivity reaction to TRODELVY. WARNINGS AND PRECAUTIONS Neutropenia: Severe, life-threatening, or fatal neutropenia can occur as early as the first cycle of treatment and may require dose modification. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm3 on Day 1 of any cycle or below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 of USPI. Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤ Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments. Hypersensitivity and Infusion-Related Reactions: TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions. Nausea and Vomiting: TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting. Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function. Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose. ADVERSE REACTIONS In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%). In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes. In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes. DRUG INTERACTIONS UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY. UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY. Please see full Prescribing Information, including BOXED WARNING. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Trodelvy (such as ASCENT-03, ASCENT-04, ASCENT-05 and ASCENT-07); uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for programs and/or indications currently under evaluation; the possibility that Gilead may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. 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点击上方蓝字 关注我们编者按近年来，靶向于TROP2的新型抗体偶联药物（ADC）在HER2阴性晚期乳腺癌（HER2- mBC）领域展现了巨大的应用潜力，我国自主研发的TROP2 ADC芦康沙妥珠单抗（Sacituzumab tirumotecan；sac-TMT，亦称SKB264/MK-2870）一路高歌猛进，成为首个获批治疗乳腺癌的国产TROP2 ADC。在获批晚期三阴性乳腺癌（TNBC）相关适应症后，近日，中国国家药品监督管理局（NMPA）药品审评中心（CDE）正式受理了芦康沙妥珠单抗治疗HR+/HER2- mBC相关适应症的新药上市申请（NDA），拟用于既往接受过内分泌治疗且在晚期或转移性阶段接受过其他系统治疗的不可切除的局部晚期或转移性HR+/HER2-乳腺癌成人患者，且被纳入优先审评，有望进一步改变我国乳腺癌的临床实践。△CDE受理截图锚定临床治疗需求为HR+/HER2- mBC寻找新的“解救者”乳腺癌是威胁我国女性健康的第一大恶性肿瘤，每年新发病例超40万，死亡病例10余万[1]；而其中有将近70%为HR+/HER2-乳腺癌[2]。作为最常见的分子亚型，HR+/HER2-乳腺癌代表了最为广泛的临床治疗需求。根据最新版的ABCC、CSCO-BC、CBCS&CSOBO等权威指南[3-5]及临床实践现状，对于内脏危象等需要快速控制疾病，以及既往内分泌治疗耐药或不适合内分泌治疗的HR+/HER2- mBC患者，可首选解救化疗，并且主要参考三阴性乳腺癌（TNBC）首选紫杉类化疗方案。经一线化疗失败的患者，后线治疗尚无标准，卡培他滨、长春瑞滨、吉西他滨、艾立布林等单药化疗的疗效有限，客观缓解率仅为14%~22.9%，生存预后较差，中位无进展生存期（PFS）仅为4.0~4.9个月[6]，亟需更有效的治疗药物以满足患者的治疗需求。近年来，不同靶点的新型抗体偶联药物（ADC）在HER2- mBC取得突破性进展，其中滋养层细胞表面抗原 2（TROP2）是较为热门的新型ADC研发靶点。临床中，大约有80%的乳腺癌存在TROP2过表达，尤其HR+/HER2-乳腺癌和TNBC的TROP2阳性表达率更高[7]。国内外已有多款TROP2 ADC正在研究开发中，此类ADC的临床应用无需治疗前检测TROP2靶点，覆盖人群更广、节省了检测费用。然而，目前国内仅有一款进口TROP2 ADC获批HR+/HER2- mBC相关适应症，主要用于经内分泌治疗且在转移性疾病阶段接受过至少2种其他系统性治疗的不可切除局部晚期或转移性HR+/HER2- mBC。因此，我们期待有国产TROP2 ADC满足更多患者的治疗需求，并且能够将治疗线序稳步向前拓展。药物机制全面升级TROP2 ADC“新势力”芦康沙妥珠单抗TROP2 ADC主要由人源化TROP2单克隆抗体、高活性载荷通过连接子偶联而成，目前开发的TROP2 ADC在药物作用机制（MOA）方面存在差异，导致疗效和安全性表现不尽相同。芦康沙妥珠单抗是我国首个自主研发且具有国际品质的TROP2 ADC，存在多方面的MOA差异化优势[8]。首先，芦康沙妥珠单抗的抗体具有高亲和力，解离平衡常数（KD，越低表明亲和力越高） 低至0.31nM，亲和力是同类TROP2 ADC的近100倍[8-9]，可大大增加肿瘤细胞内吞的药物数量。再者，芦康沙妥珠单抗具有理想的稳定性和低脱靶效应，这主要得益于两方面的MOA优势：一是使用自主研发的单侧不可逆偶联技术，使得抗体端与连接子稳定结合；二是采用了引入甲基砜结构的全新拓扑异构酶I抑制剂T030作为载荷，与连接子的稳定性更高。连接子两端的稳定性增加，能够充分避免药物提前释放到全身，减小毒副作用。此外，高药物抗体比（DAR）和旁观者效应使其肿瘤杀伤作用大大提高。芦康沙妥珠单抗的DAR高达7.4而且均质性好；在稳定到达肿瘤部位后，通过连接子pH敏感性裂解和胞内酶解的双重机制，释放具有膜透性的载荷，从而发挥强大的旁观者效应，对靶标细胞周围的肿瘤产生毒性作用。△芦康沙妥珠单抗的药物结构示意图得益于药物机制的全面升级，芦康沙妥珠单抗在HER2- mBC领域已取得一系列突破性研究进展，基于III期OptiTROP-Breast01研究[11]，芦康沙妥珠单抗已经于2024年11月在国内获批用于既往至少接受过2种系统治疗（其中至少1种针对晚期治疗）的mTNBC成人患者，并获得ABCC、CSCO-BC、CBCS&CSOBO等权威指南的推荐[3-5]；其在HR+/HER2- mBC领域的应用也令人充满期待。下一站，HR+/HER2-mBC芦康沙妥珠单抗新适应症“近在咫尺”芦康沙妥珠单抗的HR+/HER2- mBC领域已经积累了一定的循证医学证据。2023年ESMO大会的口头报告中，报道了篮子试验KL264-01的HR+/HER2- mBC队列数据[11]。该队列的患者有79%既往接受过≥2次转移性疾病化疗，100%接受过紫杉醇化疗，65.8%接受过CDK4/6抑制剂治疗。针对此类经过多线治疗的患者，芦康沙妥珠单抗仍可取得36.8%的ORR，且不同HER2表达水平、原发或继发内分泌耐药、既往是否CDK4/6i经治的患者均展现了一致的疗效获益。这些疗效数据令人惊喜，高于化疗的历史报道数据，尤其ORR提升了2~3倍；在已报道的HR+/HER2- mBC后线治疗研究中，多数TROP2 ADC的中位PFS为4.3~6.9个月[12-15]，而KL264-01研究中芦康沙妥珠单抗的中位PFS达到11.1个月。此外，芦康沙妥珠单抗的不良事件可管可控，常见的≥3治疗相关不良事件（TRAE）为中性粒细胞减少（36.6%）、白细胞减少（22%）、贫血（14.6%）等血液毒性，临床处理经验丰富，没有报告神经毒性、眼毒性和间质性肺病（ILD）等特殊不良事件。基于KL264-01研究展示的积极疗效和安全性，2025年CSCO BC诊疗指南已经将芦康沙妥珠单抗作为HR+/HER2低表达晚期乳腺癌CDK4/6i经治患者的解救治疗推荐[4]，这也是首个获指南推荐HR+/HER2- mBC治疗的国产TROP2 ADC。△KL264-01研究：芦康沙妥珠单抗治疗HR+/HER2- mBC的疗效和生存获益本次受理是基于OptiTROP-Breast02注册III期研究的积极结果。该研究旨在进一步评估芦康沙妥珠单抗对比研究者选择化疗用于HR+/HER2- mBC患者的疗效和安全性，入组患者为既往接受过至少一线（但不超过四线）化疗失败，且在任何疾病阶段接受过至少一种CDK4/6抑制剂和内分泌治疗失败的不可手术切除的局部晚期、复发或转移性HR+/HER2-（IHC 0，或IHC 1+，或IHC 2+且ISH -）乳腺癌患者。入组患者随机接受芦康沙妥珠单抗或研究者选择的化疗（艾立布林、卡培他滨、吉西他滨、长春瑞滨）。根据预设的期中分析，该研究达到主要疗效终点，与研究者选择化疗方案相比，芦康沙妥珠单抗单药疗法在主要终点由盲态独立评审委员会（BIRC）评估的PFS方面具有显著统计学意义和临床意义的改善，显著降低疾病进展或死亡风险。芦康沙妥珠单抗显示出总生存期（OS）获益趋势。△SKB264-III-10研究设计基于积累的循证医学证据，日前药企向国家药品监督管理局药品审评中心（CDE）递交了芦康沙妥珠单抗治疗HR+/HER2- mBC的新适应症上市申请（NDA），并已被纳入优先审评程序；该药物拟被用于既往接受过内分泌治疗且在晚期或转移性阶段接受过其他系统治疗的不可切除的局部晚期或转移性HR+/HER2-乳腺癌成人患者。相信随着临床研究结果的公布以及新适应症的正式获批，芦康沙妥珠单抗将进一步改变临床实践，造福更多乳腺癌患者。总结和展望芦康沙妥珠单抗在药物机制的全面升级，使其疗效和安全性均有质的提升。基于临床未被满足的治疗需求，芦康沙妥珠单抗的临床进阶之路越走越宽，从mTNBC后线治疗开始，稳步拓展至HR+/HER2- mBC，III期临床试验也由晚期治疗推进至（新）辅助治疗阶段，治疗模式则从单药到不同机制药物的多种联合探索，更多研究还在持续评估和计划开展中，芦康沙妥珠单抗有望在HER2-乳腺癌治疗发挥基石作用。△芦康沙妥珠单抗在HER2-乳腺癌中的研究布局参考文献上下滑动查看更多内容[1]郑荣寿, 陈茹, 韩冰峰, 等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2024, 46(3):221-231.DOI: 10.3760/cma.j.cn112152-20240119-00035[2]Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. Published 2014 Apr 28. doi:10.1093/jnci/dju055[3]国家肿瘤质控中心乳腺癌专家委员会,等,中国抗癌协会肿瘤药物临床研究专业委员会.中国晚期乳腺癌规范诊疗指南（2024版）[J].中华肿瘤杂志,2024,46(12):1079-1106.[4]中国临床肿瘤学会（CSCO）乳腺癌诊疗指南. 2025/中国临床肿瘤学会指南工作委员会组织编写. 北京：人民卫生出版社，2025.4.[5]中国抗癌协会乳腺癌专业委员会.中华医学会肿瘤学分会乳腺肿瘤学组.CBCS&CSOBO 乳腺癌诊治指南与规范精要本（2025版）.[6]Raheem F, Karikalan SA, Batalini F, El Masry A, Mina L. Metastatic ER+ Breast Cancer: Mechanisms of Resistance and Future Therapeutic Approaches. Int J Mol Sci. 2023;24(22):16198. Published 2023 Nov 11. doi:10.3390/ijms242216198[7]Lai J, Deng S, Cao J, et al. Identification of biomarker associated with Trop2 in breast cancer: implication for targeted therapy. Discov Oncol. 2024;15(1):413. Published 2024 Sep 6. doi:10.1007/s12672-024-01261-0[8]Cheng Y, Yuan X, Tian Q, et al.Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Front. Oncol. 12:951589. doi: 10.3389/fonc.2022.951589[9]Liu X, Deng J, Yuan Y, et al. Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer [published correction appears in Pharmacol Ther. 2023 Mar;243:108336. doi: 10.1016/j.pharmthera.2022.108336.]. Pharmacol Ther. 2022;239:108296. doi:10.1016/j.pharmthera.2022.108296[10]Binghe Xu, Yongmei Yin, Ying Fan, et al. Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): Results from the phase III OptiTROP-Breast01 study. 2024ASCO abstract 104.[11]Q. Ouyang, et al.SKB264 (MK-2870) in previously treated hormone receptor-positive (HR+)/ HER2-negative metastatic breast cancer (mBC): Results from a phase I/II, single-arm, basket trial. 2023 ESMO. Abstract 380MO.[12]Xu B, Wang S, Yan M, et al. Sacituzumab govitecan in HRHER2 metastatic breast cancer: the randomized phase 3 EVER-132-002 trial. Nat Med. 2024;30(12):3709-3716.[13]Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2019;380(8):741-751. doi:10.1056/NEJMoa1814213[14]Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2028485[15]Aditya Bardia,et al.Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple-Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study.Cancer Res (2023) 83 (5_Supplement): P6-10-03（来源：《肿瘤瞭望》编辑部）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。