Avelumab + axitinib vs sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase 3 JAVELIN Renal 101 trial.

IF 56.7 1区医学 Q1 ONCOLOGY Annals of Oncology Pub Date : 2024-12-18 DOI:10.1016/j.annonc.2024.12.008

T K Choueiri, K Penkov, H Uemura, M T Campbell, S Pal, C Kollmannsberger, J L Lee, B Venugopal, A J M van den Eertwegh, S Negrier, H Gurney, L Albiges, R Berger, J B A G Haanen, V Oyervides Juárez, B I Rini, J Larkin, F Nolè, M Schmidinger, M B Atkins, Y Tomita, B Ellers-Lenz, J Hoffman, R Sandner, J Wang, A di Pietro, R J Motzer

{"title":"Avelumab + axitinib vs sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase 3 JAVELIN Renal 101 trial.","authors":"T K Choueiri, K Penkov, H Uemura, M T Campbell, S Pal, C Kollmannsberger, J L Lee, B Venugopal, A J M van den Eertwegh, S Negrier, H Gurney, L Albiges, R Berger, J B A G Haanen, V Oyervides Juárez, B I Rini, J Larkin, F Nolè, M Schmidinger, M B Atkins, Y Tomita, B Ellers-Lenz, J Hoffman, R Sandner, J Wang, A di Pietro, R J Motzer","doi":"10.1016/j.annonc.2024.12.008","DOIUrl":null,"url":null,"abstract":"Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS).Patients and methods: Patients with untreated aRCC (any prognostic risk score) were enrolled. Primary endpoints were OS and PFS in the programmed death ligand 1-positive (PD-L1+) population. ORR, duration of response (DOR), safety, and patient-reported outcomes (PROs) were also assessed.Results: Minimum follow-up was 68 months in all patients. Median OS (95% CI) with avelumab + axitinib vs sunitinib, respectively, was 43.2 (36.5-51.7) vs 36.2 (29.8-44.2) months in the PD-L1+ population (hazard ratio [HR], 0.86 [95% CI, 0.701-1.057]; P=0.0755) and 44.8 (39.7-51.1) vs 38.9 (31.4-45.2) months in the overall population (HR, 0.88 [95% CI, 0.749-1.039]; P=0.0669). Investigator-assessed PFS remained prolonged with avelumab + axitinib vs sunitinib (5-year event-free rate [95% CI] in the overall population, 12.0% [8.9%-15.6%] vs 4.4% [2.5%-7.3%]). ORR (95% CI) in the overall population was 59.7% (55.0%-64.3%) with avelumab + axitinib vs 32.0% (27.7%-36.5%) with sunitinib; DOR (95% CI) was ≥5 years in 16.4% (12.0%-21.4%) vs 9.2% (4.6%-15.7%), respectively. Rates of grade ≥3 treatment-related adverse events were 66.8% vs 61.5%, respectively. PROs were similar between arms.Conclusions: JAVELIN Renal 101 provides the longest follow-up to date for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase 3 trial in aRCC. OS analyses favored avelumab + axitinib vs sunitinib but did not reach statistical significance; subsequent treatment may have impacted results. Avelumab + axitinib provided long-term efficacy benefits vs sunitinib, including prolonged PFS, a nearly doubled ORR, and more durable responses, with a manageable long-term safety profile.","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.annonc.2024.12.008","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS).

Patients and methods: Patients with untreated aRCC (any prognostic risk score) were enrolled. Primary endpoints were OS and PFS in the programmed death ligand 1-positive (PD-L1+) population. ORR, duration of response (DOR), safety, and patient-reported outcomes (PROs) were also assessed.

Results: Minimum follow-up was 68 months in all patients. Median OS (95% CI) with avelumab + axitinib vs sunitinib, respectively, was 43.2 (36.5-51.7) vs 36.2 (29.8-44.2) months in the PD-L1+ population (hazard ratio [HR], 0.86 [95% CI, 0.701-1.057]; P=0.0755) and 44.8 (39.7-51.1) vs 38.9 (31.4-45.2) months in the overall population (HR, 0.88 [95% CI, 0.749-1.039]; P=0.0669). Investigator-assessed PFS remained prolonged with avelumab + axitinib vs sunitinib (5-year event-free rate [95% CI] in the overall population, 12.0% [8.9%-15.6%] vs 4.4% [2.5%-7.3%]). ORR (95% CI) in the overall population was 59.7% (55.0%-64.3%) with avelumab + axitinib vs 32.0% (27.7%-36.5%) with sunitinib; DOR (95% CI) was ≥5 years in 16.4% (12.0%-21.4%) vs 9.2% (4.6%-15.7%), respectively. Rates of grade ≥3 treatment-related adverse events were 66.8% vs 61.5%, respectively. PROs were similar between arms.

Conclusions: JAVELIN Renal 101 provides the longest follow-up to date for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase 3 trial in aRCC. OS analyses favored avelumab + axitinib vs sunitinib but did not reach statistical significance; subsequent treatment may have impacted results. Avelumab + axitinib provided long-term efficacy benefits vs sunitinib, including prolonged PFS, a nearly doubled ORR, and more durable responses, with a manageable long-term safety profile.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

求助全文

约1分钟内获得全文去求助

来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.