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根据2015ASCO年会报告的一项3期临床试验的结果，化疗新药etirinotecan pegol表现出改善晚期乳腺癌患者生存的趋势(摘要号1001）。医脉通对此进行了报道。

尽管etirinotecan pegol(NKTR-102; Nektar制药)治疗没有达到预先设定的使所有患者获得显著获益，但亚组患者，尤其是那些大脑或肝转移的患者，使用etirinotecan pegol可显著提高总生存时间。

“化疗仍然是许多晚期乳腺癌患者主要的治疗方法，”佛罗里达州杰克逊维尔Mayo Clinic癌症中心副主任Edith A. Perez博士在一次采访中说。“所以我们正在寻找新型化疗药物有更好的药物动力学，并且没有神经系统不良反应，很少的骨髓抑制或心脏毒性。”

Etirinotecan pegol是第一个长效拓扑异构酶1抑制剂，可持续提供活性代谢物SN-38。

BEACON研究，纳入852名晚期乳腺癌患者，患者的ER/HER-2状态不定。Perez和他的同事将患者随机分为接受etirinotecan pegol组和医生选择化疗组。在医生选择化疗组中,40%的患者接受了eribulin，23%使用了长春瑞滨，18%接受吉西他滨，15%使用紫杉烷类和4%使用了ixabepalone。OS为主要研究终点。

研究人员观察到，所有人群中etirinotecan pegol组的中位OS为(12.4个月)，比医生选择化疗组(10.3个月)，提高了2.1月(HR = 0.87;P =.08)。

在预先选定的脑转移患者亚组(n = 67)中，etirinotecan pegol组的中位OS为10个月，而医生选择化疗组中位OS为4.8月(HR = 0.51;P<.01)。而且，接受etirinotecan pegol组中脑转移患者OS达到12个月的比例，较医生选择化疗组更高(44.4% vs.19.4%)。

Etirinotecan pegol还表现出对肝转移患者的活性(n = 456)。那些使用etirinotecan pegol的亚组患者的中位OS为10.9个月，而标准化疗组为8.3个月(HR = 0.73;P = .002)。

“我们证实对于肝脏或脑转移患者，该药可显著改善患者的总生存”，Perez说。“而且值得注意的是，这个新化疗药物的毒性与市场上常用的标准化疗药物相比更低，因此患者的生存质量更高。对于这两个较难治疗的亚组患者，使用该药让我们看到一些生存方面的改善。”

etirinotecan pegol组比医生选择化疗组发生3级或以上药物不良反应的比例更低(48% vs. 63%)。etirinotecan pego组最常见的不良反应为腹泻(9.6%)、中性粒细胞减少(9.6%)、贫血(4.7%)和呼吸困难(4.4%)。

严重的神经病变，医生选择化疗组发生率为3.7%，而etirinotecan pego组为0.5%。tirinotecan pegol组秃头症发生率比医生选择化疗组更低(10% vs. 23%)。

“对于该药还需要更多的研究,但如果这种药物现在上市,我们真的会考虑将其用于病人身上“Perez说。“公司正与药品监管机构协商如何将其上市。我们观察到，该药可显著改善脑转移患者总生存。我希望公司进行更大的研究，纳入更多的脑转移患者，因为我觉得这是可行的。因为该药有很好的抗癌活性。”——Anthony SanFilippo

医脉通编译自：Novel chemotherapy drug demonstrates activity in advanced breast cancer, Healio, June 5, 2015

会议专题》》》2015年ASCO年会专题报道

摘要原文

Phase III trial of etirinotecan pegol (EP) versus Treatment of Physician’s Choice (TPC) in patients (pts) with advanced breast cancer (aBC) whose disease has progressed following anthracycline (A), taxane (T) and capecitabine (C): The BEACON study.

Abstract Number: 1001

Background: EP is the first long-acting topoisomerase 1 inhibitor providing sustained levels of SN38. In Phase II, EP demonstrated a 29% ORR following a median of 2 prior regimens for aBC. BEACON study (NCT01492101) randomized (1:1) pts with aBC and progressive disease following A,T and C to EP (145 mg/m2q3w over 90 minutes) or TPC (any of 7 cytotoxics). 

Methods: Eligible pts had any ER/HER2 and ECOG 0-1; stable brain metastases were allowed. 852 pts enrolled over 20 months and reached target for events in Dec2014. The choice of TPC: eribulin 40%, vinorelbine 23%, gemcitabine 18%, taxane 15%, ixabepilone 4%. Primary efficacy endpoint was overall survival (OS) by 2-sided log-rank test stratified by region, prior eribulin and receptor status; the study had 90% power to detect a target Hazard Ratio (HR) of 0.77. Circulating tumor cells (CTCs) were isolated in -80% of pts and analyzed for target-specific pharmacodynamic biomarkers. This is the first presentation of these data.

Results: EP provided a 2.1 month improvement in median OS over TPC (12.4 vs 10.3 months; HR 0.87, p = 0.08). In a pre-specified subgroup of 67 pts with brain metastases, EP showed an improvement of 5.2 months in median OS (10.0 vs 4.8 months; HR 0.51, p < 0.01); the proportion of pts with brain metastases alive at 12-mo survival was higher with EP (44.4% vs 19.4%). Similarly, in pts with liver metastases (n = 456) median OS improved with EP (10.9 vs 8.3 months; HR 0.73, p = 0.002). Grade (G) ≥ 3 AEs were lower with EP (48%) than TPC (63%). Common G ≥ 3 AE with EP: diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%) and fatigue (4.5%); TPC: neutropenia (30.5%), anemia (4.7%) and dyspnea (4.4%). Severe neuropathy: 3.7% of pts (TPC) vs 0.5% (EP). Alopecia was less with EP (10% vs 23%). Data on efficacy in CTC biomarker defined sub-groups (TOP1, TOP2) will be presented.

Conclusions: EP provided a clinically meaningful benefit to pts with late-stage aBC, although this did not reach statistical significance. In pts with brain metastases, median OS doubled; improved survival was also seen in other pt subsets. Toxicity with EP was less than with TPC. Clinical trial information: NCT01492101

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