Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.
Hua Xu, Xin Yao, Zhisong He, Hong Luo, Guiling Li, Jianming Guo, Lei Diao, Yu Fan, Yuan Li, Jiquan Fan, Xiaoyi Hu, Puhan Lu, Haiyan Shi, Keyan Chen, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su, Dingwei Ye
{"title":"Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.","authors":"Hua Xu, Xin Yao, Zhisong He, Hong Luo, Guiling Li, Jianming Guo, Lei Diao, Yu Fan, Yuan Li, Jiquan Fan, Xiaoyi Hu, Puhan Lu, Haiyan Shi, Keyan Chen, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su, Dingwei Ye","doi":"10.1007/s11523-024-01120-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).</p><p><strong>Objective: </strong>We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).</p><p><strong>Patients and methods: </strong>Eligible patients had pathologically confirmed advanced ccRCC. Patients received fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus sintilimab 200 mg every 3 weeks in 3-week cycles. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1.</p><p><strong>Results: </strong>By March 31, 2023, 42 patients (median age 58.9 years; 81.0% male) had been treated in the RCC cohort. Among treatment-naive patients (n = 22), confirmed ORR was 68.2% (95% confidence interval [CI] 45.1-86.1). The median progression-free survival (PFS) was not reached, and 18-month PFS rate was 59.4%. Among previously treated patients (n = 20), the confirmed ORR was 60.0% (95% CI 36.1-80.9), and the median PFS was 15.9 (95% CI 5.4-19.3) months. All patients had adverse events related to study treatment, 52.4% of which were grade ≥ 3 in severity. Treatment-related adverse events with an incidence of ≥ 40% included proteinuria, hypothyroidism, hypercholesterolemia, hypertriglyceridemia, and hypoalbuminemia.</p><p><strong>Conclusions: </strong>Fruquintinib plus sintilimab demonstrated promising efficacy in advanced ccRCC and was well tolerated. A phase III study (FRUSICA-02) using this combination regimen in patients with previously treated advanced ccRCC is ongoing.</p><p><strong>Trial registration number: </strong>The study was registered with ClinicalTrials.gov (NCT03903705).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"113-125"},"PeriodicalIF":4.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Targeted Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11523-024-01120-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/13 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).
Objective: We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).
Patients and methods: Eligible patients had pathologically confirmed advanced ccRCC. Patients received fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus sintilimab 200 mg every 3 weeks in 3-week cycles. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1.
Results: By March 31, 2023, 42 patients (median age 58.9 years; 81.0% male) had been treated in the RCC cohort. Among treatment-naive patients (n = 22), confirmed ORR was 68.2% (95% confidence interval [CI] 45.1-86.1). The median progression-free survival (PFS) was not reached, and 18-month PFS rate was 59.4%. Among previously treated patients (n = 20), the confirmed ORR was 60.0% (95% CI 36.1-80.9), and the median PFS was 15.9 (95% CI 5.4-19.3) months. All patients had adverse events related to study treatment, 52.4% of which were grade ≥ 3 in severity. Treatment-related adverse events with an incidence of ≥ 40% included proteinuria, hypothyroidism, hypercholesterolemia, hypertriglyceridemia, and hypoalbuminemia.
Conclusions: Fruquintinib plus sintilimab demonstrated promising efficacy in advanced ccRCC and was well tolerated. A phase III study (FRUSICA-02) using this combination regimen in patients with previously treated advanced ccRCC is ongoing.
Trial registration number: The study was registered with ClinicalTrials.gov (NCT03903705).
期刊介绍:
Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes:
Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches.
Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways.
Current Opinion articles that place interesting areas in perspective.
Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations.
Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement.
Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.