Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, 80 Vas. Sofias Ave, 115 28, Athens, Greece.
Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloníki, Greece.
Int J Clin Oncol. 2019 Apr;24(4):411-419. doi: 10.1007/s10147-018-1361-9. Epub 2018 Oct 29.
Vascular endothelial growth factor (VEGF) targeting represents the standard first-line therapy for metastatic renal-cell carcinoma (mRCC), while blocking the mammalian target of rapamycin (mTOR) is effective in relapsed disease. Since continuing blockade of VEGF may be of value, we studied the combination of bevacizumab with temsirolimus in mRCC patients relapsing after first-line treatment.
A prospective, phase II study of the combination of bevacizumab (10 mg/kg, every 2 weeks) with temsirolimus (25 mg weekly) in patients with mRCC who failed first-line anti-VEGF treatment. 6-month progression-free survival (PFS) rate was the primary end point. The association of VEGFa, VEGFR2, fibroblast growth factor (FGF) b, platelet-derived growth factor receptor (PDGFR) a and PDGFRb with prognostic factors and outcomes were also studied.
39 patients were enrolled. First-line therapy included: sunitinib (n = 16), bevacizumab/interferon (n = 12), pazopanib (n = 10), sorafenib (n = 1). After a median follow-up of 37 months, 6-month PFS rate was 50.9% [95% confidence interval (CI) 33.8-65.7], median time to progression 6.8 months (95% CI 5.5-9.2) and median overall survival (OS) 18.2 months (95% CI 12.9-27.2). Objective response rate was 27%. The most common AEs were metabolic (33%), renal (8%) and gastrointestinal (GI) (7%). The most common grade 3-5 AEs were GI (18%), infections (14%) and metabolic (25%). Toxicity was the most frequent cause of treatment discontinuation (40%). FGFb levels were associated with OS.
In concert with recent data, our study confirms the efficacy of anti-VEGF/anti-mTOR combination in mRCC relapsing after anti-VEGF therapy. Toxicity was considerable leading to high rate of treatment discontinuations.
ClinicalTrials.gov: NCT01264341.
血管内皮生长因子（VEGF）靶向治疗是转移性肾细胞癌（mRCC）的标准一线治疗方法，而阻断哺乳动物雷帕霉素靶蛋白（mTOR）在复发疾病中有效。由于持续阻断 VEGF 可能具有价值，我们研究了贝伐珠单抗联合替西罗莫司在一线治疗后复发的 mRCC 患者中的联合应用。
前瞻性、Ⅱ期研究贝伐珠单抗（10mg/kg，每 2 周）联合替西罗莫司（25mg 每周）在一线抗 VEGF 治疗失败的 mRCC 患者中的应用。6 个月无进展生存期（PFS）率为主要终点。还研究了 VEGFa、VEGFR2、成纤维细胞生长因子（FGF）b、血小板衍生生长因子受体（PDGFR）a 和 PDGFRb 与预后因素和结果的关系。
39 例患者入组。一线治疗包括：舒尼替尼（n=16）、贝伐珠单抗/干扰素（n=12）、帕唑帕尼（n=10）、索拉非尼（n=1）。中位随访 37 个月后，6 个月 PFS 率为 50.9%（95%CI 33.8-65.7），中位进展时间为 6.8 个月（95%CI 5.5-9.2），中位总生存期（OS）为 18.2 个月（95%CI 12.9-27.2）。客观缓解率为 27%。最常见的 AE 为代谢（33%）、肾脏（8%）和胃肠道（GI）（7%）。最常见的 3-5 级 AE 为 GI（18%）、感染（14%）和代谢（25%）。毒性是导致治疗中断最常见的原因（40%）。FGFb 水平与 OS 相关。
与最近的数据一致，我们的研究证实了抗 VEGF/抗 mTOR 联合治疗在一线抗 VEGF 治疗后复发的 mRCC 中的疗效。毒性相当大，导致治疗中断率较高。
ClinicalTrials.gov：NCT01264341。
