Laboratory of Experimental Oncology, Department of Oncology, University of Leuven, Leuven, Belgium; Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, Institut Universitaire Hématologie, Paris, France.
Clin Genitourin Cancer. 2018 Jun;16(3):e605-e612. doi: 10.1016/j.clgc.2017.10.017. Epub 2017 Nov 7.
We previously described 4 molecular subtypes of metastatic clear cell renal cell carcinoma (mccRCC), named ccrcc1-4 (Beuselinck et al, 2015). These have both prognostic and predictive value for patients treated with first-line sunitinib, with distinctive objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The ccrcc2 and ccrcc3 tumors have the best outcomes, followed by ccrcc1 and then ccrcc4. We hypothesized that these molecular subtypes would show similar outcomes with first-line pazopanib treatment.
We classified 28 mccRCC tumors treated with pazopanib as first-line therapy, as described previously. The primary endpoints were PFS and OS from the start of pazopanib. A secondary endpoint was ORR. Because there were only 2 ccrcc3 tumors, they were pooled with the ccrcc2 tumors for outcome analysis.
PFS was 9 months for the ccrcc2 and ccrcc3 tumors, 5 months for ccrcc1 tumors, and 3 months for the ccrcc4 tumors (P = .011). The corresponding OS duration was 69, 19, and 5 months (P = .003). The corresponding ORR was 50%, 33%, and 0%. The corresponding mean tumor size decreased by 34%, 6%, and 2% (P = .032). The ccrcc1-4 classification was a stronger predictor of outcome than the International Metastatic Renal Cell Carcinoma Database Consortium score on univariate analysis (P = .011 vs. P = .094 for PFS and P = .003 vs. .013 for OS). Both remained independent on bivariate analysis.
The molecular subtypes of mccRCC are associated with outcome on pazopanib as first-line therapy. The prognostic and predictive value of the ccrcc1-4 molecular classification requires validation in prospective trials.
我们之前描述了 4 种转移性透明细胞肾细胞癌（mccRCC）的分子亚型，分别命名为 ccrcc1-4（Beuselinck 等人，2015 年）。这些对于接受一线舒尼替尼治疗的患者具有预后和预测价值，具有独特的客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。ccrcc2 和 ccrcc3 肿瘤的结局最好，其次是 ccrcc1，然后是 ccrcc4。我们假设这些分子亚型在接受一线帕唑帕尼治疗时会有类似的结果。
我们按照之前的描述，将 28 例接受帕唑帕尼一线治疗的 mccRCC 肿瘤进行分类。主要终点是从开始使用帕唑帕尼起的 PFS 和 OS。次要终点是 ORR。由于只有 2 例 ccrcc3 肿瘤，因此将其与 ccrcc2 肿瘤一起进行结局分析。
ccrcc2 和 ccrcc3 肿瘤的 PFS 为 9 个月，ccrcc1 肿瘤为 5 个月，ccrcc4 肿瘤为 3 个月（P=0.011）。相应的 OS 持续时间为 69、19 和 5 个月（P=0.003）。相应的 ORR 为 50%、33%和 0%。相应的平均肿瘤大小分别减少了 34%、6%和 2%（P=0.032）。在单变量分析中，ccrcc1-4 分类是比国际转移性肾细胞癌数据库联盟评分更好的预后预测指标（P=0.011 对 PFS，P=0.003 对 OS）。两者在双变量分析中仍然是独立的。
mccRCC 的分子亚型与帕唑帕尼作为一线治疗的疗效相关。ccrcc1-4 分子分类的预后和预测价值需要在前瞻性试验中验证。
