Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Department of Hematology-Oncology, Chungbuk National University Hospital, Cheongju, Korea.
Cancer Res Treat. 2017 Oct;49(4):1001-1011. doi: 10.4143/crt.2016.546. Epub 2017 Jan 13.
This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC).
Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR).
Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (EGFR) mutation (p=0.122), EGFR fluorescence in situ hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005).
There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.
本 II 期研究旨在评估与阿法替尼单药治疗相比，辛伐他汀联合阿法替尼治疗既往接受过治疗的非腺癌非小细胞肺癌（NA-NSCLC）患者是否具有临床获益。
接受过一种或两种化疗方案治疗后进展的晚期 NA-NSCLC 患者被随机分配至辛伐他汀（40mg/天）+阿法替尼（40mg/天）（AS）组或阿法替尼（A）组。主要终点为缓解率（RR）。
共纳入 68 例患者（AS 组 36 例，A 组 32 例）。AS 组的 RR 为 5.7%（95%CI，0.7 至 19.2），A 组为 9.4%（95%CI，2.0 至 25.0）（p=0.440）。AS 组和 A 组的中位无进展生存期（PFS）分别为 1.0 个月和 3.6 个月（p=0.240），总生存期分别为 10.0 个月和 7.0 个月（p=0.930）。两组中最常见的不良事件均为皮疹、口腔炎和腹泻。A 组 3 级或 4 级腹泻发生率高于 AS 组（18.8%比 5.6%）。在所有患者中，接受阿法替尼治疗的中位 PFS 与表皮生长因子受体（EGFR）突变状态（p=0.122）、EGFR 荧光原位杂交（p=0.944）或 EGFR 免疫组化（p=0.976）均无相关性。然而，皮疹严重程度与阿法替尼进展风险显著相关（皮疹等级≥2 与等级<2 的风险比，0.44；95%CI，0.25 至 0.78；p=0.005）。
在 NA-NSCLC 患者中，AS 组与 A 组的疗效无显著差异。
