De Velasco Guillermo, Xie Wanling, Donskov Frede, Albiges Laurence, Beuselinck Benoit, Srinivas Sandy, Agarwal Neeraj, Lee Jae Lyun, Brugarolas James, Wood Lori A, Rha Sun-Young, Kollmannsberger Christian, North Scott, Kanesvaran Ravindran, Rini Brian I, Broom Reuben, Yamamoto Haru, Kaymakcalan Marina D, Heng Daniel Y C, Choueiri Toni K
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA; Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain.
Deparment of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA.
Clin Genitourin Cancer. 2017 Jun;15(3):403-410.e2. doi: 10.1016/j.clgc.2017.01.005. Epub 2017 Jan 12.
A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason for discontinuation of first-line (1L) therapy is unknown.
Patients from 15 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) centers who started 2L targeted therapy were included and the reason for discontinuation of 1L therapy retrospectively collected. Treatment outcomes of 2L, including response, time to treatment failure, and overall survival (OS) were assessed.
In total, 1124 patients were identified: 866 patients (77%) discontinued 1L VEGF-TT because of disease progression, and 208 patients (19%) because of toxicity. The reason for discontinuation of 1L therapy did not differ according to IMDC risk group. Compared with patients who stopped 1L VEGF-TT because of disease progression, patients who stopped because of toxicity had greater clinical benefit (nonprogressive disease as best response) in 2L treatment (68% vs. 56%; adjusted odds ratio, 1.58; 95% confidence interval [CI], 1.07-2.35; P = .023) and longer OS (17.4 vs. 11.2 months; adjusted hazard ratio, 0.69; 95% CI, 0.56-0.84; P = .0002) adjusted for type of therapy, time to initiation of 2L treatment, IMDC risk group, and number of metastases at initiation of 2L treatment.
mRCC patients who discontinue 1L VEGF-TT because of toxicity have better outcomes with 2L therapy than patients who stop therapy because of disease progression. These findings should be taken into consideration when designing clinical trials for 2L therapies in mRCC.
相当一部分转移性肾细胞癌（mRCC）患者因毒性反应而停用血管内皮生长因子靶向治疗（VEGF-TT）。基于一线（1L）治疗停药原因接受二线（2L）靶向治疗的患者，其临床结局是否存在差异尚不清楚。
纳入来自15个国际转移性肾细胞癌数据库联盟（IMDC）中心开始接受2L靶向治疗的患者，并回顾性收集1L治疗停药原因。评估2L治疗结局，包括缓解情况、治疗失败时间和总生存期（OS）。
共识别出1124例患者：866例患者（77%）因疾病进展停用1L VEGF-TT，208例患者（19%）因毒性反应停药。1L治疗停药原因在IMDC风险组间无差异。与因疾病进展停用1L VEGF-TT的患者相比，因毒性反应停药的患者在2L治疗中具有更大的临床获益（最佳缓解为疾病无进展）（68%对56%；调整优势比，1.58；95%置信区间[CI]，1.07 - 2.35；P = .023）以及更长的OS（17.4个月对11.2个月；调整风险比，0.69；95% CI，0.56 - 0.84；P = .0002），对治疗类型、开始2L治疗的时间、IMDC风险组以及开始2L治疗时的转移灶数量进行了校正。
因毒性反应停用1L VEGF-TT的mRCC患者接受2L治疗的结局优于因疾病进展停药的患者。在设计mRCC的2L治疗临床试验时应考虑这些发现。
