David Geffen School of Medicine at UCLA and Jonsson Comprehensive Cancer Center, 2825 Santa Monica Blvd, Suite 200, Santa Monica, CA, USA.
University of Minnesota, Masonic Cancer Center, 420 Delaware Street SE, NHH 3-112, CCRB 3-130 Minneapolis, MN 55455, USA.
Lung Cancer. 2018 Sep;123:91-98. doi: 10.1016/j.lungcan.2018.06.013. Epub 2018 Jun 22.
This open-label, randomized phase II trial evaluated antitumor efficacy of an antiestrogen, fulvestrant, in combination with human epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in advanced non-small cell lung cancer (NSCLC) patients.
Patients with advanced or metastatic NSCLC, ECOG 0-2, previous chemotherapy unless patient refusal, and no prior EGFR-directed therapy were randomized 2:1 to erlotinib 150 mg oral daily plus 500 mg intramuscular fulvestrant on day 1, 15, 29 and every 28 days thereafter or erlotinib alone 150 mg oral daily. The primary end point was objective response rate (ORR); secondary endpoints included progression free survival (PFS) and overall survival (OS).
Among 106 randomized patients, 100 received at least one dose of study drug. ORR was 16.4% (11 of 67 patients) for the combination versus 12.1% (4 of 33 patients) for erlotinib (p = 0.77). PFS median 3.5 versus 1.9 months [HR = 0.86, 95% CI (0.52-1.43), p = 0.29] and OS median 9.5 versus 5.8 months [HR = 0.92, 95% CI (0.57-1.48), p = 0.74] numerically favored the combination. In an unplanned subset analysis, among EGFR wild type patients (n = 51), but not EGFR mutant patients (n = 17), median PFS was 3.5 versus 1.7 months [HR = 0.35, 95% CI (0.14-0.86), p = 0.02] and OS was 6.2 versus 5.2 months [HR = 0.72, 95% CI (0.35-1.48), p = 0.37] for combined therapy versus erlotinib, respectively. Notably, EGFR WT patients were more likely to be hormone receptor-positive (either estrogen receptor α- and/or progesterone receptor-positive) compared to EGFR mutant patients (50% versus 9.1%, respectively) (p = 0.03). Treatment was well tolerated with predominant grade 1-2 dermatologic and gastrointestinal adverse effects.
Addition of fulvestrant to erlotinib was well tolerated, with increased activity noted among EGFR wild type patients compared to erlotinib alone, albeit in an unplanned subset analysis.
这项开放标签、随机的 II 期试验评估了抗雌激素氟维司群联合表皮生长因子受体（EGFR）抑制剂厄洛替尼在晚期非小细胞肺癌（NSCLC）患者中的抗肿瘤疗效。
患者为晚期或转移性 NSCLC，ECOG 0-2，既往化疗（除非患者拒绝），且无既往 EGFR 靶向治疗史，按 2:1 随机分组接受厄洛替尼 150mg 口服每日一次加氟维司群 500mg 肌肉注射，第 1、15、29 天和此后每 28 天一次，或厄洛替尼单药 150mg 口服每日一次。主要终点为客观缓解率（ORR）；次要终点包括无进展生存期（PFS）和总生存期（OS）。
在 106 例随机患者中，100 例至少接受了一剂研究药物。联合治疗组的 ORR 为 16.4%（67 例患者中的 11 例），而厄洛替尼组为 12.1%（33 例患者中的 4 例）（p=0.77）。PFS 中位数分别为 3.5 个月和 1.9 个月[HR=0.86，95%CI（0.52-1.43），p=0.29]，OS 中位数分别为 9.5 个月和 5.8 个月[HR=0.92，95%CI（0.57-1.48），p=0.74]，联合治疗组略占优势。在一项未计划的亚组分析中，在 EGFR 野生型患者（n=51）中，而非 EGFR 突变型患者（n=17）中，PFS 中位数分别为 3.5 个月和 1.7 个月[HR=0.35，95%CI（0.14-0.86），p=0.02]，OS 中位数分别为 6.2 个月和 5.2 个月[HR=0.72，95%CI（0.35-1.48），p=0.37]，联合治疗组优于厄洛替尼。值得注意的是，与 EGFR 突变型患者相比，EGFR WT 患者更有可能为激素受体阳性（雌激素受体α和/或孕激素受体阳性）（分别为 50%和 9.1%）（p=0.03）。治疗耐受性良好，主要为 1-2 级皮肤和胃肠道不良事件。
与厄洛替尼单药治疗相比，氟维司群联合厄洛替尼耐受性良好，在 EGFR 野生型患者中观察到活性增加，尽管这是在一项未计划的亚组分析中。
