Tivozanib

– Cumulative data of three Phase 3 studies demonstrate greater exposure of tivozanib is associated with increased clinical benefit – – Patient Reported Outcomes were numerically better for patients receiving tivozanib in a second line setting versus third line – BOSTON, Feb. 18, 2025 /PRNewswire/ -- AVEO Oncology, an LG Chem company ("AVEO"), is a biopharmaceutical company that is trying to provide differentiated solutions to improve cancer patients lives, presented two posters during the 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) meeting highlighting continued data for tivozanib, a next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) designed to block the VEGF pathway by selectively inhibiting all three VEGF receptors. "Following the TiNivo-2 study results presentation at ESMO 2024 and publication in The Lancet, we were excited to share this data with the oncology community at ASCO GU 2025," said Michael Bailey, president and Chief Executive Officer. "These data build on the robust clinical evidence for tivozanib generated over different studies that have consistently demonstrated clinical benefit and tolerability in the advanced RCC population." Poster title: " Integrated efficacy and safety exposure response (ER) analysis of tivozanib (TIVO) for the treatment of renal cell cancer (RCC)." – (Abstract: 461; Poster: D29) AVEO presented data from an exploratory analysis evaluating the efficacy and safety exposure response relationship of tivozanib from three Phase 3 trials that have been conducted with TIVO: TIVO-1, TIVO-3, and TiNivo-2. The objective of the analysis was to better understand the relationship between tivozanib exposure with progression free survival (PFS), tumor size (TS), and hypertension (HTN) using pharmacokinetic (PK) and exposure response (ER) modeling in metastatic renal cell carcinoma (RCC). The analysis demonstrated a strong correlation between higher exposure of tivozanib and improvements in PFS while the exposure level of both the standard dose of 1.34 mg dose and low dose 0.89 mg of tivozanib was associated with a similar incidence of hypertension. Poster Title: "Patient-reported outcomes (PROs) for tivozanib (TIVO) + nivolumab (NIVO) vs TIVO monotherapy in patients with renal cell carcinoma (RCC) following an immune checkpoint inhibitor (ICI): results of the phase 3 TiNivo-2 study." – (Abstract: 459; Poster: D27) AVEO presented a poster with data from an exploratory analysis evaluating patient reported outcomes (PROs) from the TiNivo-2 study. TiNivo-2 is a randomized, Phase 3 trial designed to assess the efficacy and safety of a PD-1 inhibitor combination following disease progression on or after prior PD-1/PD-L1 therapy. While the study did not meet its primary endpoint of demonstrating a benefit of adding nivolumab to tivozanib versus tivozanib alone after prior immune checkpoint inhibitor (ICI) exposure, clinically meaningful outcomes were observed with tivozanib monotherapy (1.34 mg) as a second-line (2L) and third-line (3L) treatment following ICI therapy. The analysis used the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index-Disease-Related Symptoms (FKSI-DRS) and European Organization for Research and Treatment of Cancer (EORTC) QLQ C30 questionnaires, administered at baseline, day 1 of each cycle, and at the end of treatment, to collect patient outcomes. The analysis indicated that tivozanib maintained the FKSI-DRS and EORTC QLQ-C30 mean scores over time in both treatment arms. Importantly, in the tivozanib monotherapy arm, the proportion of patients who had improvement in FKSI-DRS and EORTC QLQ-C30 scores was numerically better in patients receiving 2L versus 3L treatment, while the portion of patients with a deterioration was smaller in the 2L than in the 3L. INDICATIONS FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Hypertension was reported in 45% of patients (22% ≥ Grade 3). Hypertensive crises were reported in 0.8% of patients. Do not initiate FOTIVDA in patients with uncontrolled hypertension. Monitor for hypertension and treat as needed. Reduce the FOTIVDA dose for persistent hypertension not controlled by anti-hypertensive medications. Discontinue FOTIVDA for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis. Cardiac failures were reported in 1.6% of patients (1% ≥ Grade 3); 0.6% of events were fatal. Monitor for signs or symptoms of cardiac failure during treatment with FOTIVDA. Manage with dose interruption, dose reduction, or discontinuation. Cardiac ischemia were reported in 3.2% of patients; 0.4% of events were fatal. Arterial thromboembolic events were reported in 2.0% of patients, including death due to ischemic stroke (0.1%). Closely monitor patients at risk for, or who have a history of these events. Discontinue FOTIVDA in patients who develop severe arterial thromboembolic events, such as myocardial infarction and stroke. Venous Thrombotic Events (VTE) were reported in 2.4% of patients, including 0.3% fatal events. Closely monitor patients who are at increased risk for these events. Discontinue in patients who develop serious VTEs. Hemorrhagic Events were reported in 11% of patients; 0.2% of events were fatal. Use FOTIVDA with caution in patients who are at risk for or who have a history of bleeding. Proteinuria was reported in 8% of patients (2% = Grade 3). Monitor during treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or interrupt treatment. Discontinue in patients who develop nephrotic syndrome. Gastrointestinal (GI) Perforation including fatal cases, has been reported in patients receiving FOTIVDA. Monitor for symptoms of GI perforation or fistula formation periodically throughout treatment with FOTIVDA. Permanently discontinue FOTIVDA in patients who develop severe or life-threatening GI perforation. Thyroid Dysfunction events were reported in 11% of patients (0.3% ≥ Grade 3). Monitor thyroid function before and during treatment with FOTIVDA. Wound Healing Complications: Withhold FOTIVDA for at least 24 days prior to elective surgery and do not administer for at least 2 weeks after major surgery and until adequate wound healing is observed. Reversible Posterior Leukoencephalopathy Syndrome (RPLS) can occur with FOTIVDA. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue if signs or symptoms of RPLS occur. Embryo-fetal Toxicity: FOTIVDA can cause fetal harm. Advise patients of the potential risk to a fetus, to avoid becoming pregnant and to use contraception during treatment and for one month after the last dose of FOTIVDA. Advise males with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose of FOTIVDA. Allergic Reaction to Tartrazine: FOTIVDA 0.89 mg capsule contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients. ADVERSE REACTIONS Common adverse reactions include fatigue/asthenia, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. Serious adverse reactions include bleeding (3.5%), venous thromboembolism (3.5%), arterial thromboembolism (2.9%), acute kidney injury (2.3%), and hepatobiliary disorders (2.3%). DRUG INTERACTIONS Avoid coadministration with strong CYP3A4 inducers. USE IN SPECIFIC POPULATIONS Advise women not to breastfeed during treatment and for at least 1 month after the last dose. The recommended dosage for patients with end-stage renal disease has not been established. Reduce the FOTIVDA dose for patients with moderate hepatic impairment. The recommended dosage in patients with severe hepatic impairment has not been established. To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or . Please see full Prescribing Information for FOTIVDA® (tivozanib). About FOTIVDA® (tivozanib) FOTIVDA® (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021, for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies, based on data from the TIVO-3 trial comparing FOTIVDA to sorafenib. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner Recordati UK Ltd. for the treatment of adult patients with advanced RCC. FOTIVDA was discovered by Kyowa Kirin. About AVEO Pharmaceuticals, Inc. AVEO is an oncology-focused biopharmaceutical company committed to delivering medicines that provide a better life for patients with cancer. AVEO currently markets FOTIVDA® (tivozanib) in the U.S. for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. AVEO continues to develop FOTIVDA in immuno-oncology and other novel targeted combinations in RCC and other indications, and has other investigational programs in clinical development. AVEO became a wholly owned subsidiary of LG Chem Life Sciences USA, Inc. on January 19, 2023. AVEO continues to operate under the AVEO Oncology, an LG Chem company, name. About LG Chem, Ltd. and LG Chem Life Sciences LG Chem, Ltd. (LG Chem) is a leading global chemical company with a diversified business portfolio in the key areas of petrochemicals, advanced materials, and life sciences. The company manufactures a wide range of products from high-value added petrochemicals to renewable plastics, specializing in cutting- edge electronic and battery materials, as well as drugs and vaccines to deliver differentiated solutions for its customers. LG Chem Life Sciences develops, manufactures, and globally commercializes pharmaceutical products, with a focus on Oncology, Immunology, and Metabolic diseases. Our mission is to transform people's lives through inspiring science and leading innovation. For more information, please visit . Contacts Media: John F. Kouten JFK Communications, Inc. [email protected] (908) 227-4714 SOURCE AVEO, an LG Chem company WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

- 年度盘点 - 2024年度晚期肾癌治疗重要进展 盛锡楠教授 编者按：道阻且长，行则将至；行而不辍，未来可期。近年来，肾癌领域的部分免疫治疗遭遇“滑铁卢”，没有达到主要终点；但随着更多靶向、免疫等治疗药物的研究进展，晚期肾癌治疗取得了长足进步。尤其多项靶免联合治疗的大型Ⅲ期研究相继取得成功，标志着晚期肾癌一线治疗进入了靶免联合治疗时代。2024年晚期肾癌取得了多项突破，我们特邀北京大学肿瘤医院盛锡楠教授分享重要研究进展，或许可为未来的肾癌治疗和研究提供更多参考借鉴。 01 透明细胞肾细胞癌一线治疗 自2018年底公布第一项免疫联合用于晚期肾透明细胞癌的随机对照Ⅲ期临床研究以来，目前已经有多项随机对照Ⅲ期临床研究显示免疫联合治疗可以改善晚期肾癌的一线治疗预后。2023年ESMO大会公布了特瑞普利单抗联合阿昔替尼的RENOTORCH研究结果，显示联合治疗组的中位PFS达到18.0个月（舒尼替尼单药组为9.8个月），降低疾病进展或死亡风险35%。2024年4月国家药品监督管理局（NMPA）批准特瑞普利单抗联合阿昔替尼用于中高危不可切除或转移性肾细胞癌的一线治疗，同时也纳入2024版中国临床肿瘤学会（CSCO）肾癌诊疗指南一线治疗的Ⅰ级推荐，标志着国内晚期肾癌正式步入靶向联合免疫治疗的时代。随着一线免疫联合方案的增加，未来需要通过预测标志物等筛选优势获益人群，为患者提供个体化治疗策略。 PD-L1单抗联合靶向治疗进展 自PD-1与PD-L1单抗为代表的免疫检查点抑制剂被引入晚期肾透明细胞癌的治疗后，已先后开展了多项随机对照3期临床研究，但大部分为以PD-1单抗为基础的联合方案，而以PD-L1单抗为基础的联合方案仅有IMmotion151研究和JAVELIN RENAL 100研究两项。IMmotion151研究未能证实阿替利珠单抗联合贝伐单抗显著优于舒尼替尼靶向治疗。 虽然JAVELIN RENAL100研究显示，阿昔替尼联合阿维鲁单抗显著改善一线治疗的无进展生存（PFS）时间，并由此获批美国FDA晚期肾癌一线治疗适应证。但2024 ASCO年会所公布的最终生存分析结果显示[1]，经过68个月的中位随访时间后，联合治疗在PD-L1阳性患者中的中位总生存（mOS）为43.2个月（对照组为36.2个月，HR=0.86）；在意向性治疗（ITT）人群中的mOS为44.8个月（对照组为38.9个月，HR=0.88）。尽管联合治疗可以延长总生存期近7个月，但是仍没有达到统计学显著性界值，为靶向联合PD-L1单抗的应用埋下了阴霾。 △ PD-L1阳性人群和总人群中的OS分析 2024年ESMO大会，公布了由北京大学肿瘤医院和中国医学科学院肿瘤医院牵头的ETER-100研究中期分析结果[2]，这项试验是国内第2项晚期肾透明细胞癌的Ⅲ期临床研究，也是全球第3项靶向联合PD-L1单抗免疫治疗的大型研究，比较了安罗替尼联合PD-L1单抗贝莫苏拜单抗（TQB2450）对比舒尼替尼作为晚期肾细胞癌（RCC）患者一线治疗的效果。主要终点是PFS。今年ESMO大会公布的结果显示[2]，在平均随访19.52个月后，靶免联合组显著延长了PFS（风险比HR 0.53；P<0.0001；中位PFS 18.96个月 vs 9.76个月），并提高了ORR（71.59% vs 25.10%；P<0.0001）。目前总生存数据尚不成熟，初步来看是有利于靶向联合免疫治疗组。研究在安全性方面和之前的研究数据基本类似。当前的研究结果显示，免疫疗法联合TKI对于晚期肾癌患者的总生存期具有显著的延长作用，这一发现重新点燃了PD-L1单抗联合靶向治疗晚期肾癌的希望。 △ 两个治疗组的PFS分析 不同IMDC危险分层人群的获益分析 目前晚期肾癌的一线免疫联合治疗数据均支持IMDC中高危患者免疫联合治疗较既往单独靶向治疗可获得显著获益，这一结论也在近年来多项3期临床研究的随访数据以及专为中高危人群设计的RENOTORCH研究中得到验证。 2024年ASCO-GU公布的CheckMate 9ER研究55个月随访结果表明[3]，对于未经治疗的aRCC患者，纳武利尤单抗联合卡博替尼方案的PFS（16.4个月vs. 8.4个月，HR 0.58）、OS（46.5个月vs. 36.0个月，HR 0.77）和ORR（55.7% vs. 27.7%）均优于舒尼替尼。基于IMDC分层，在低危人群中，联合治疗组的mOS未取得显著获益（HR=1.10）；在中/高危人群中，联合治疗组的mPFS（15.4个月 vs 7.1个月，HR=0.56）和mOS显著获益（43.9个月 vs 29.3个月，HR=0.73）；联合治疗组的ORR达52.6%，显著优于舒尼替尼组。不同转移部位疗效评估，肝、骨、肺转移的肾细胞癌患者，PFS、OS、ORR均能从联合治疗组中显著获益。因此，国内外指南仍推荐免疫联合治疗作为中高危晚期肾透明细胞癌患者的一线治疗，而对于低危人群，靶向药物仍然可以作为治疗选择之一。 △ CheckMate 9ER研究IMDC低危人群的PFS、OS、ORR分析 但并非所有低危患者都不能从免疫联合治疗中获益。2024年ASCO-GU大会公布了CheckMate-214研究的8年随访数据[4]，显示纳武利尤单抗+伊匹木单抗继续显示出较舒尼替尼具有统计学意义和临床意义的长期生存和持久的缓解获益。在ITT人群中，双免联合组的中位OS更长（52.7个月vs. 37.8个月；HR 0.72，95%CI 0.62，0.83）；在IMDC低危患者中，虽然双免治疗组初始获益并不明显，但经过长期随访，双免治疗组的OS获益凸显（77.9个月 vs 66.7个月），并且双免联合具有更加持久（DOR：61.5 vs 33.2月）和深度（CR率：16% vs 8%）的缓解。尽管随访时间延长，但联合治疗组并未出现新的安全性信号。因此，NCCN指南、ESMO指南等国外指南均将双免疫治疗纳入IMDC低危人群的推荐治疗。 △ CheckMate 214研究中IMDC低危人群的OS和DOR分析 2024 ASCO年会公布了一项IMDC真实世界研究[5]，该研究从传统意义的低危患者中筛选出极低危患者，其标准定位为从初诊至接受全身治疗的时间≥3年、无脑肝或骨转移、卡氏评分90或100的患者。数据分析显示，IMDC极低危人群接受双免疫、靶向联合免疫以及单独靶向治疗的ORR分别为23.5%、58.1%和55%，2年OS率分别为71.3%、87.2%和92.1%；而低危患者的ORR分别为35%、51.4%和37.9%，2年OS率分别为86.4%、84.1%和81.1%。这表明极低危患者仍然能从单独抗血管靶向药物治疗中获益，而非极低危患者似乎从联合免疫治疗中更能获益。该结果仍然需要进一步的前瞻性试验和更长时间的随访来验证，但对于生物学行为较差的患者，即使是低危患者，仍然可以考虑积极的免疫联合治疗。 △ IMDC真实世界研究的OS分析 因此，对于晚期肾透明细胞癌的一线治疗，随着可选择方案的增加，不仅仅需要考虑危险分层，还需要结合转移部位等疾病特征。当然，如果有更好的预测标记物，将会有更好的优化治疗选择。 筛选获益预测因素 由于目前缺乏预测性生物标志物，因此需要进一步明确最有可能从靶免联合治疗中受益的患者。2024年在ESMO大会公布的CheckMate 9ER研究的生物标志物分析结果表明[6]，蛋白质岩藻糖基化和唾液酸化机制或许可潜在驱动aRCC患者纳武利尤单抗联合卡博替尼和舒尼替尼耐药。参与补体级联反应和脂质代谢的血清糖蛋白可预测纳武利尤单抗联合卡博替尼和舒尼替尼治疗aRCC的缓解情况。 2024年欧洲泌尿外科年会（EAU）公布了NORA真实世界研究中纳武利尤单抗联合伊匹木单抗一线治疗晚期肾细胞癌患者OS的预后因素[7]。结果提示，中位随访11.9个月，13.3%的患者OS<3个月，86.7%的患者OS≥3个月，其中OS<3个月组较OS≥3个月组的患者基线有更多的不良因素：IMDC评分更差（高危28.6% vs 25.3%）、ECOG PS评分更高（≥2分，25.7% vs 4.8%）、Karnofsky PS更低（≥70分，62.9% vs 82.5%）、既往肾切除率更低（54.3% vs 64.6%）、转移负荷更高，基线平均转移器官数更多（2.1 vs 1.8）。随着未来更长时间随访与更多研究的探索，未来可能会出现更多有关OS预后因素的相关数据。 02 透明细胞肾细胞癌一线治疗失败后的选择 晚期肾透明细胞癌的治疗已经进入免疫联合时代，一线治疗失败后虽然有众多未用过的方案可供选择，如继续靶向或靶向联合免疫，但目前尚无高等级循证医学证据支持相应选择。因此，一线治疗后如何选择成为临床待解的难题，也是未来临床研究的热点。 序贯靶向方案 针对免疫联合治疗失败后的二线选择，2023 ASCO年会公布了一项卡博替尼联合阿替利珠单抗对比卡博替尼单药的随机对照3期CONTACT-03研究，结果证实联合免疫未能优于卡博替尼单药治疗。 TiNivo-2研究是一项全球多中心、随机、开放标签的3期研究[8]，分析了纳武利尤单抗联合替沃扎尼或替沃扎尼单药治疗经1~2种治疗（包括免疫治疗）后出现进展患者的疗效。主要终点是PFS；关键次要终点是OS，其他次要终点包括PFS、ORR、DoR和安全性/耐受性。研究共纳入343名患者，随机接受替沃扎尼联合纳武利尤单抗（n=171）或替沃扎尼（n=172）。研究结果表明，联合治疗组和单药组的PFS分别为5.7个月和7.4个月，OS分别为17.7个月和22.1个月。两组ORR接近，分别为33%和34%。结果提示，对于晚期肾细胞癌患者，不推荐再次尝试ICI治疗。此外，研究数据明确指出，在免疫治疗后，替沃扎尼单药治疗展现出了一定的疗效，为这一阶段的患者提供了潜在的治疗选择。因此，对于晚期肾透明细胞癌一线接受免疫联合后的治疗，继续免疫联合靶向药物不能获益，而选择单独靶向治疗已经成为共识。 △ TiNivo-2研究ITT人群PFS分析 新型靶向药物 近年来，缺氧诱导因子（HIF）-2α成为了肾癌靶向治疗的关注焦点。贝组替凡是一种小分子药物，能够结合并稳定HIF的α亚基，从而阻止其进入细胞核并激活下游基因的表达。这种作用机制使得贝组替凡能够抑制VHL相关肿瘤的血管生成和细胞增殖，进而达到控制肿瘤生长的目的。这一发现为VHL相关肿瘤的治疗提供了新的思路和方法，也为贝组替凡的研发奠定了坚实的基础。2024年11月，NMPA批准贝组替凡上市，用于治疗VHL相关肾细胞癌等肿瘤，为患者提供了新的治疗选择。 贝组替凡单药对比依维莫司的LITESPARK-005研究共入组746名患者（贝组替凡374名，依维莫司372名）。既往数据证实，贝组替凡可显著改善免疫检查点抑制剂和抗血管生成药物治疗后进展的晚期ccRCC患者的无进展生存期（HR 0.75，P＜0.001）和客观缓解率（21.9% vs. 3.5%，P＜0.00001），而依维莫司则未达到该水平。2024年ESMO大会更新PFS获益，并公布了OS结果[9]。与依维莫司相比，贝组替凡持续具有PFS获益（5.6个月vs. 5.6个月；HR 0.75；95% CI 0.63~0.88）；贝组替凡的12个月和24个月估计PFS率更优（12个月：33.7% vs 17.6%；24个月：17.5% vs 4.1%）。贝祖替凡治疗组的中位OS为21.4个月，依维莫司组为18.2个月（HR 0.92；95% CI 0.77~1.10；P=0.18）。12个月时估计OS率分别为67.9% vs. 65.8%，24个月时估计OS率分别为45.2% vs. 41.2%。结果表明，与接受依维莫司治疗相比，接受贝组替凡治疗的晚期ccRCC患者可获得更好的PFS和ORR结局。 △ 贝组替凡和依维莫司治疗组的PFS和OS分析 其他的HIF-2α抑制剂如2024 ASCO年会公布的DFF332[10]，在中位既往治疗线数为2的40例晚期肾癌患者中获得了5%的ORR和52.5%的疾病控制率（DCR）。2024 ESMO年会公布的NKT2152[11]，作为中位既往三线治疗的100例晚期肾癌患者的后线治疗，获得了20%的ORR和7.4个月的PFS期，剂量递增组的中位PFS期为9.2个月。 相较上述HIF-2α抑制剂的单药疗效数据，HIF-2α抑制剂联合治疗方案更值得关注，并在初期研究中获得了更好的疗效。由北京大学肿瘤医院与全国多中心研究团队开展的LITESPARK-010是一项I期、2队列、开放标签研究的队列1的研究结果，这项研究旨在分析使用贝组替凡联合仑伐替尼（联合或不联合帕博利珠单抗）治疗中国晚期ccRCC患者的疗效和安全性。2024年ASCO大会报告的初步数据显示[12]，贝组替凡联合仑伐替尼对于既往接受过治疗的中国ccRCC患者而言，抗肿瘤活性良好。贝组替凡120 mg联合仑伐替尼20 mg的安全性与各自药物的安全性概况一致。这一结果表明，对于多线治疗失败的患者，这种联合治疗方案具有较好的初步疗效。 △ LITESPARK-010研究的PFS和OS分析 03 非透明细胞肾细胞癌治疗 非透明细胞肾细胞癌因其显著不同的分子特征和临床行为，仍需要个体化及创新性的治疗策略提高治疗效果，改善远期生存。 靶免治疗 2024年ASCO-GU大会公布的KEYNOTE-B61研究[13]表明，仑伐替尼联合帕博利珠单抗用于晚期nccRCC一线治疗具有良好的疗效。延长随访结果显示，ORR为50.6%，DCR为82.3%，中位DOR为19.5个月，中位PFS为17.9个月，中位OS尚未达到，安全性可控。亚组分析结果表明，这一联合方案在不同组织类型的nccRCC中均显示出不错的ORR，为患者提供了新的治疗选择。此外，仑伐替尼与帕博利珠单抗的联合治疗方案在改善患者生存质量和延长生存期方面也表现出明显优势。这为nccRCC患者提供了一种新的治疗策略，但仍需进一步研究以确定其在不同患者群体中的最佳应用。 △ KEYNOTE-B61研究的ORR、DOR、PFS和OS分析 2024年ASCO大会公布了一项开放标签的、单臂、国内多中心、II期试验[14]，评估信迪利单抗联合阿昔替尼在富马酸水合酶缺乏型肾细胞癌中的疗效和安全性。研究的主要终点为ORR和PFS。在38名可进行疗效评估的患者中，研究者观察到了显著的疗效。结果显示，ORR达60.5%，疾病控制率达86.8%，中位PFS为19.83个月。这种联合方案疗效良好，未来可通过评估FH基因突变，预测靶免联合治疗的疗效，从而实现更精准的个体化治疗。 △ 信迪利单抗联合阿昔替尼治疗组的ORR和PFS分析 双免治疗 2024 ESMO年会公布了晚期非透明细胞癌双免疫治疗的随机对照2期SUNNIFORECAST研究结果[15]，显示纳武利尤单抗联合伊匹木单抗方案相对于常规治疗方案，PFS（5.52个月 vs 5.65个月）和OS（42.4个月 vs 33.9个月）均未观察到统计学差异，PD-L1表达阳性（CPS>1%）亚组获益更为显著。 △ SUNNIFORECAST研究的PFS和PS分析 在另一项特异性双抗的研究中[16]，22例非透明细胞肾细胞癌患者接受一线PM8002/BNT327治疗，中位随访9.0个月，ORR为36.4%。不同亚型中，乳头状癌ORR最高，DCR为90.9%，中位PFS为15.1个月。此外，研究中对于双抗药物的3级以上不良反应发生率更低（41.5%，KEYNOTE-426研究为75.8%），表现出了很好的发展前景。 △ PM8002/BNT327治疗nccRCC的ORR、DCR和PFS分析 随着靶免治疗及双免治疗的不断发展，晚期肾癌患者的生存取得了显著进展。未来，随着预测标志物的探索，有望进行个体化治疗，进一步改善患者生存。 参考文献 上下滑动查看更多内容 [1]. Robert J. Motzer, et al. Avelumab + axitinib vs sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC): Final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3 trial. ASCO 2024. 4508. [2]. Xinan Sheng, et al. Anlotinib in combined with anti-PD-L1 antibody Benmelstobart(TQB2450) versus sunitinib in first-line treatment of advanced renal cell carcinoma (RCC) -A randomized, open-label, phase III study (ETER100). ESMO 2024 Abstract LBA76. [3]. Maria Teresa Bourlon, et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Results from 55-month follow-up of the CheckMate 9ER trial.  2024 ASCO GU, Abs 362. [4]. Tannir NM, Escudier B, McDermott DF, et al. Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial. 2024 ASCO GU, Abstr 363. [5]. Martin Zarba, et al. Systemic treatments in favorable and very favorable risk metastatic renal cell carcinoma (mRCC): Real world evidence from the International mRCC Database Consortium (IMDC). J Clin Oncol 42, 2024 (suppl 16; abstr 4514) [6]. Braun, D. A., et al. 1694MO Novel serum glycoproteomic biomarkers predict response to nivolumab plus cabozantinib (NIVO+ CABO) versus sunitinib (SUN) in advanced RCC (aRCC): Analysis from CheckMate 9ER. Annals of Oncology 35 (2024): S1012-S1013. [7]. Bedke J, Grünwald V, Müller-Huesmann H, et al. Prognostic factors for Overall Survival (OS) in patients receiving First-line (1L) Nivolumab plus Ipilimumab (NIVO+IPI) for advanced/metastatic Renal Cell Carcinoma (aRCC) in a real-world setting in Germany. 2024 EAU, Abstr A0829. [8]. Choueiri T K, Albiges L, Barthélémy P, et al. Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study[J]. 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Belzutifan plus lenvatinib (len) for Chinese patients (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): Preliminary results of cohort 1 of the phase 1 LITESPARK-010 study[J]. ASCO 2024. 4537 [13]. Martin H Voss, et al. First-line pembrolizumab plus lenvatinib for non–clear cell renal carcinomas (nccRCC): Extended follow-up of the phase 2 KEYNOTE-B61 study. 2024 ASCO GU 2. [14]. Hao Zeng, Xingming Zhang, Jiayu Liang, et al, Sintilimab plus axitinib for advanced fumarate hydratase-deficient renal cell carcinoma: A multi-center, open-label, single-arm, phase II study (SAFH) [J]. JCO 42, 4523-4523(2024).DOI:10.1200/JCO.2024.42.16_suppl.4523. [15]. L. Bergmann et al, LBA75 - Prospective randomised phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer: Results of the SUNNIFORECAST trial. Annals of Oncology (2024) 35 (suppl_2): 1-72. 10.1016/annonc/annonc1623 [16]. Xinan Sheng, et al, 1692P - A phase Ib/IIa trial to evaluate the safety and efficacy of PM8002/ BNT327, a bispecific antibody targeting PD-L1 and VEGF-A, as a monotherapy in patients with advanced renal cell. Annals of Oncology (2024) 35 (suppl_2): S1012-S1030. 10.1016/annonc/annonc1609 盛锡楠 教授 主任医师，教授，博士生导师 北京大学肿瘤医院泌尿肿瘤内科副主任 中国抗癌协会泌尿生殖肿瘤整合康复专业委员会副主任委员 中国抗癌协会泌尿系统肿瘤专业委员会常委 中国临床肿瘤学会(CSCO)理事 中国临床肿瘤学会肾癌专家委员会常委兼秘书长 中国临床肿瘤学会尿路上皮癌专家委员会常委 国家肿瘤质控中心膀胱癌质控专家委员会委员 北京肿瘤防治研究会泌尿肿瘤分委会候任主任委员 北京抗癌协会泌尿生殖肿瘤专委会青委会主任委员 北京医学会肿瘤分会常委 （来源：《肿瘤瞭望-泌尿时讯》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。