
ESMO 2026
2026 年 10 月 23–27 日 · Madrid · 共 4873 条
LITESPARK-012
★★★20 人 · 22 条
本事件热度走势
当前热度 1·可比范围峰值 2(10月26日 04:00)·近 24 小时可比范围变化 –·当前参与者 3
晚期透明细胞肾癌(ccRCC)的一线标准治疗是以免疫检查点抑制剂为基础的双联方案,包括双免联合或免疫联合VEGF-TKI[3]。在这条主干上做加法的尝试有两个方向:一是HIF-2α抑制剂belzutifan,它是目前唯一获批的HIF-2α抑制剂,2021年获批用于VHL病相关肾癌,2023年又获批多线治疗进展后的晚期散发性RCC,而多数ccRCC存在VHL缺失或失活、导致HIF-2α持续激活并驱动血管生成与肿瘤生长,靶点的生物学依据相当扎实[5][6];二是CTLA-4抑制剂quavonlimab[1]。III期LITESPARK-012(NCT04736706)的设计目的,正是在帕博利珠单抗+仑伐替尼基础上加用belzutifan或quavonlimab,检验三联能否成为新的标准治疗[1];其早期依据来自Ib/II期KEYMAKER-U03子研究03A,后者在未经治疗的晚期ccRCC中探索了quavonlimab/帕博利珠单抗+仑伐替尼、帕博利珠单抗+仑伐替尼+belzutifan等方案,并以帕博利珠单抗+仑伐替尼为同期对照,主要终点为BICR评估的ORR[2]。
本次ESMO26现场报道的正是LITESPARK-012的III期结果:共入组1688例未经治疗的晚期ccRCC患者,随机接受帕博利珠单抗+仑伐替尼+belzutifan(A组)、MK-1308A+仑伐替尼(B组,即CTLA-4阻断方向,方案中对应quavonlimab[1])或帕博利珠单抗+仑伐替尼对照,双重主要终点为BICR评估的PFS和OS。结果A组PFS HR 1.08(0.93–1.26)、OS HR 1.04(0.87–1.25);B组PFS HR 1.07(0.92–1.25)、OS HR 1.12(0.94–1.35);因不良事件导致的停药率A组51.6%、B组51.4%、对照组36.2%。结论明确:无论加入belzutifan还是CTLA-4阻断,均未带来疗效改善,帕博利珠单抗+仑伐替尼仍是一线标准治疗。
这一阴性读数的价值,在于把“三联优于双联”的假设放在一线III期对照下给出了否定答案:尽管HIF-2α通路在VHL失活的ccRCC中有明确的致病作用[6],早期研究中三联方案也显示出活性[2],但都没有转化为PFS或OS获益,代价则是停药率从36.2%抬升到51%以上——而belzutifan已知的在靶不良事件贫血以及低氧本就需要在治疗中监测[5],三联方案的耐受性负担是绕不开的现实问题。现场评论同时点出另一条线索:LITESPARK-011(IO经治后belzutifan+仑伐替尼)才是对HIF-2α更干净的检验,属另一项研究,不应与本次读数混同。
需要留意的局限:本研究为随机开放标签设计,现场帖明确说明其内容仅基于ESMO网站公开的摘要整理,除双主要终点的HR与停药率外,ORR、具体安全性谱、亚组分析与随访时长等细节均未披露,最终判断有待完整数据发表。
- 1.LITESPARK-012: pembrolizumab plus lenvatinib with or without belzutifan or quavonlimab for advanced renal cell carcinoma · Future Oncol 2023
- 2.Novel pembrolizumab-based treatments as first-line therapy in advanced clear-cell renal cell carcinoma: substudy 03A of the open-label, umbrella platform, phase I/II KEYMAKER-U03 trial · Ann Oncol 2026
- 3.Treatment Landscape of Renal Cell Carcinoma · Curr Treat Options Oncol 2023
- 4.The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation · Trends Biochem Sci 2025
- 5.Belzutifan for the treatment of renal cell carcinoma · Ther Adv Med Oncol 2025
- 6.Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma · Cancers (Basel) 2024
OncoAlert@OncoAlert Gil Morgan, MD@weoncologists 引用@OncoAlert 4Sight Abstracts to be Presented at #ESMO26 First-Line Pembrolizumab + Lenvatinib + Belzutifan or MK-1308A + Lenvatinib in Advanced RCC: The Randomized Open-Label Phase 3 LITESPARK-012 Study @DrChoueiri @tompowles1 @MVossMD @ERPlimackMD @HowardGurney @brian_rini 🔬 Phase 3 (n=1688), untreated advanced ccRCC: pembrolizumab + lenvatinib + belzutifan (Arm A) or MK-1308A + lenvatinib (Arm B) vs pembrolizumab + lenvatinib. Dual primary: PFS by BICR and OS. ➡️ Arm A: PFS HR 1.08 (0.93–1.26); OS HR 1.04 (0.87–1.25) ➡️ Arm B: PFS HR 1.07 (0.92–1.25); OS HR 1.12 (0.94–1.35) ➡️ Discontinuation due to AEs: 51.6% (A), 51.4% (B), 36.2% (control) ✅ Neither belzutifan nor CTLA-4 blockade added to pembrolizumab + lenvatinib improved efficacy; pembrolizumab + lenvatinib remains a 1L SOC. #KidneyCancer 🎙️ Toni Choueiri 👥 Thomas Powles · Martin Voss · Elizabeth Plimack · Howard Gurney · Yue Song · Rodolfo Perini · Karla Rodriguez-Lopez · Brian Rini (4Sight Made solely from Abstracts publicly available at the ESMO website) Pinging Our Faculty @tompowles1, @apolo_andrea, @neerajaiims, @montypal, @Silke_Gillessen, @AOmlin, @PGrivasMDPhD, @TiansterZhang, @amerseburger, @DrDanielHeng, @HHammersMD, @scocmem, @AndreaNecchi, @AmandaNizamMD, @drenriquegrande, @nataliagandur, @AlbigesL, @cdanicas, @declangmurphy, @seanmmcbride, @shilpaonc, @DrRanaMcKay, @scserendipity1, @DrYukselUrun, @ravikanesvaran, @BraunMDPhD, @EfstathiouEleni, @mzugman, @crisbergerot, @niklas_kluemper
OncoAlert@OncoAlert Yüksel Ürün@DrYukselUrun 引用@📢 #ESMO26 concomitant paper - Pembrolizumab plus lenvatinib with belzutifan or quavonlimab as first-line therapy for advanced renal-cell carcinoma: randomized open-label phase 3 LITESPARK-012 study. 🔗https://tinyurl.com/3mx946h6 @brian_rini @tompowles1
Aya Mohamed | MSc, MD 🎗@Dr_Oncologista Toni Choueiri, MD@DrChoueiri Dra. María Natalia Gandur Quiroga@nataliagandur 引用@🚨 #ESMO26 #Podium2Screen: LITESPARK-012 in advanced #RCC Our @OncoAlert founding faculty @DrChoueiri presents ➡️ Adding belzutifan or CTLA-4 blockade (quavonlimab) to pembrolizumab + lenvatinib did NOT improve PFS, OS or ORR (n=1688) @tompowles1 @MVossMD @ERPlimackMD @HowardGurney @brian_rini ➡️ Higher discontinuation rates in the triplet arms Pembro + lenvatinib remains a 1L standard 👇 #KidneyCancer Pinging Our Faculty @DrChoueiri, @tompowles1, @apolo_andrea, @neerajaiims, @montypal, @Silke_Gillessen, @AOmlin, @brian_rini, @PGrivasMDPhD, @TiansterZhang, @amerseburger, @DrDanielHeng, @HHammersMD, @scocmem, @AndreaNecchi, @AmandaNizamMD, @drenriquegrande, @nataliagandur, @AlbigesL, @cdanicas, @declangmurphy, @seanmmcbride, @shilpaonc, @DrRanaMcKay, @scserendipity1, @DrYukselUrun, @ravikanesvaran, @BraunMDPhD, @EfstathiouEleni, @mzugman, @crisbergerot, @niklas_kluemper @Markuseckstein3
Dr Rishabh Jain@DrRishabhOnco 引用@🚨 ESMO 2026 | TOP 10 GU CANCER TRIALS TO WATCH! From perioperative immunotherapy and AR pathway intensification to HIF-2α inhibition and long-term survival updates, GU oncology is set for some major presentations at #ESMO26. Here are my Top 10, grouped by subspecialty. 👇 🔵 PROSTATE CANCER 1️⃣ DASL-HiCaP (LBA4) Can adding darolutamide to ADT + radiotherapy improve outcomes in very high-risk localized prostate cancer? 2️⃣ PROTEUS (LBA53) Perioperative apalutamide + ADT in high-risk localized prostate cancer. Important additional data from the PROTEUS programme. 3️⃣ CAPItello-281 (LBA56) Updated overall survival with capivasertib + abiraterone in PTEN-deficient mHSPC. Could AKT inhibition redefine biomarker-driven treatment? 4️⃣ PEACE-1 (2215O) Long-term survival outcomes with abiraterone-based treatment intensification in de novo metastatic castration-sensitive prostate cancer. 🟢 BLADDER / UROTHELIAL CANCER 5️⃣ VOLGA (LBA2) One of the biggest presentations at ESMO 2026! Can perioperative durvalumab ± tremelimumab with neoadjuvant enfortumab vedotin improve outcomes in cisplatin-ineligible muscle-invasive bladder cancer? 6️⃣ KEYNOTE-866 (4735O) Perioperative pembrolizumab + gemcitabine/cisplatin in cisplatin-eligible MIBC. Will the detailed results clarify the role of adding immunotherapy to conventional perioperative chemotherapy? 7️⃣ ENERGIZE / CA017-078 (4736O) Does adding perioperative nivolumab to cisplatin-based chemotherapy improve outcomes in MIBC? 🟠 RENAL CELL CARCINOMA 8️⃣ LITESPARK-011 (3587O) Belzutifan + lenvatinib versus cabozantinib following prior PD-(L)1 therapy in advanced RCC. Can a HIF-2α inhibitor combination improve treatment outcomes? 9️⃣ LITESPARK-012 (3586O) Belzutifan- or quavonlimab-containing regimens with pembrolizumab + lenvatinib in first-line advanced RCC. Important efficacy and safety data for next-generation combinations. 🔟 KEYNOTE-564 (3589RO) Final prespecified analysis of adjuvant pembrolizumab in clear-cell RCC. How durable is the benefit with extended follow-up? 🔬 ALSO ON MY RADAR • PE-PE: Perioperative immunotherapy in oligometastatic RCC • KEYNOTE-B15: ctDNA analysis in MIBC • TALAPRO-3: Molecular and patient-reported outcomes • NIAGARA: Molecular subtype analysis • SWOG S2200: Papillary RCC 🔥 THREE BIG QUESTIONS FOR ESMO 2026 🔹 Will perioperative treatment strategies redefine management of MIBC? 🔹 Can treatment intensification and biomarker selection improve prostate cancer outcomes? 🔹 Will HIF-2α combinations reshape advanced RCC treatment sequencing? 📌 Pre-congress watchlist. Not all trials are expected to report positive results. Which GU trial has the greatest potential to change your clinical practice? 👇 @myesmo @ESMO_open @ASCO @oncoalert #ESMO26 #GUOncology #ClinicalTrials #Oncology
Yüksel Ürün@DrYukselUrun 引用@LITESPARK-12 tested Len/pem/bel (VEGF/PD1/HIF) vs Len/pem in 1st line RCC #ESMO26 (supported by a RII +ve PFS R2 @AlbigesL @crisuarez08). In the R3 both PFS and OS hasd HRs~1 with ⬆️ tox for triplets. Belzutifan doublets seem active so why do the triplets fail. It’s likely due to the increased toxic compromising dose intensity of the extremely active Len/pem (2 yr PFS). There seems a limit to tolerable drug intensity- triplets (COSMIC313 too) maybe a step too far. @OncoAlert @DrChoueiri
Mirrors of Medicine@mirrorsmed UroToday.com@urotoday Martin ZapataLaguado@zapatalaguadomd Stanley Zhou@stanleytor International Urology Cancer Summit@urologysummit レ点🧬💉💊@m0370 引用@First-line Pembrolizumab Plus Lenvatinib Plus Belzutifan or MK-1308A Plus Lenvatinib in Advanced RCC: Randomized Open-label Phase 3 LITESPARK-012 Study. Presented by @DrChoueiri @DanaFarber. #ESMO26 written coverage by @rksayyid @UAUrology > https://bit.ly/4yFu33m #KidneyCancer #RCC @myESMO
ScienceLink@sciencelinkonco Rashid K. Sayyid@RKSayyid OncLive.com@OncLive Álvaro Pinto@dralvaropinto LITESPARK-012:一线 mRCC 的三联疗法未能改善生存期。更多并不总是更好。而且在这种情况下,通常会更具毒性。 #ESMO26
Kohji Takemura, MD@KohjiToncol Annals of Oncology@Annals_Oncology MeDucation@MeDucationai 引用@As always, terrific list from @OncoAlert to provide guidance on which #GU abstracts amongst the many at #ESMO26! @PGrivasMDPhD @TiansterZhang @shilpaonc @tompowles1 @neerajaiims @brian_rini @uromigosjapan @Uromigos @DrChoueiri