提示: 手机请竖屏浏览!

氟维司群联合阿那曲唑治疗转移性乳腺癌的患者总生存期
Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer


Rita S. Mehta ... 肿瘤 • 2019.03.28
相关阅读
• 指导乳腺癌辅助治疗的临床和基因组风险 • alpelisib治疗有PIK3CA突变的激素受体阳性晚期乳腺癌 • 新辅助化疗联合贝伐单抗治疗HER2阴性乳腺癌 • 帕博利珠单抗治疗ER+/HER2-转移性乳腺癌 • 曲妥珠单抗-美坦新偶联物治疗残留浸润性HER2阳性乳腺癌

双剑合璧——内分泌联合治疗改善转移性乳腺癌总生存

 

马飞

国家癌症中心/中国医学科学院肿瘤医院内科

 

2019年3月28日,《新英格兰医学杂志》(NEJM)发表了Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer一文(N Engl J Med 2019;380:1226-34)。在最后一例患者入组近10年后,作者们在此文报告了氟维司群联合阿那曲唑一线治疗转移性乳腺癌这一临床试验(S0226)的最终结果。

查看更多

摘要


背景

我们之前报告,患激素受体阳性转移性乳腺癌的绝经后患者被随机分组,分别接受芳香化酶抑制剂阿那曲唑联合选择性雌激素受体下调剂氟维司群一线治疗,或者接受阿那曲唑单独一线治疗,结果表明联合治疗组的无进展生存期较长,总生存期略长。我们在本文中报告了最终的生存结局。

 

方法

我们将患者随机分组,分别接受阿那曲唑单独治疗或氟维司群+阿那曲唑联合治疗。根据接受他莫昔芬辅助治疗的情况对随机化进行分层。通过双侧分层时序检验和Cox回归进行生存分析。在全部患者和患者亚组中比较了两组的疗效和安全性。

 

结果

在被随机分组的707例患者中,694例有可用于分析的数据。联合治疗组349例女性患者中的247例(71%)死亡,中位总生存期为49.8个月,而阿那曲唑单独治疗组345例女性患者中的261例(76%)死亡,中位总生存期为42.0个月,差异显著(死亡的风险比,0.82;95%置信区间[CI],0.69~0.98;时序检验P=0.03)。在两层的亚组分析中,在既往未接受过他莫昔芬治疗的女性患者中,联合治疗组的总生存期比阿那曲唑单独治疗组长(中位数,分别为52.2个月和40.3个月;风险比,0.73;95% CI,0.58~0.92);在既往接受过他莫昔芬治疗的女性患者中,两组的总生存期相似(中位数,分别为48.2个月和43.5个月;风险比,0.97;95% CI,0.74~1.27)(对于交互作用,P=0.09)。两组中3至5级长期毒性作用的发生率相似。阿那曲唑单独治疗组约45%的患者交叉后接受了氟维司群治疗。

 

结论

虽然在阿那曲唑单独治疗期间发生疾病进展的大量患者交叉后接受了氟维司群治疗,但与阿那曲唑单独治疗组相比,阿那曲唑加用氟维司群仍与长期生存期延长相关。结果提示,在既往未接受过辅助内分泌治疗的患者中,获益尤其显著(由美国国立癌症研究所[National Cancer Institute]和阿斯利康资助;在ClinicalTrials.gov注册号为NCT00075764)。





作者信息

Rita S. Mehta, M.D., William E. Barlow, Ph.D., Kathy S. Albain, M.D., Ted A. Vandenberg, M.D., Shaker R. Dakhil, M.D., Nagendra R. Tirumali, M.D., Danika L. Lew, M.A., Daniel F. Hayes, M.D., Julie R. Gralow, M.D., Hannah M. Linden, M.D., Robert B. Livingston, M.D., and Gabriel N. Hortobagyi, M.D.
From the Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange (R.S.M.); the SWOG Statistics and Data Management Center (W.E.B., D.L.L.) and Seattle Cancer Care Alliance and University of Washington Medical Center (J.R.G., H.H.L.) — both in Seattle; Loyola University Chicago Stritch School of Medicine, Maywood, IL (K.S.A.); London Health Sciences Centre and the National Cancer Institute of Canada Clinical Trials Group, London, ON, Canada (T.A.V.); the Cancer Center of Kansas and Wichita National Cancer Institute Community Oncology Research Program (NCORP), Wichita (S.R.D.); Kaiser Permanente NCORP, Portland, OR (N.R.T.); the University of Michigan, Ann Arbor (D.F.H.); the University of Arizona Cancer Center, Tucson (R.B.L.); and the University of Texas M.D. Anderson Cancer Center, Houston (G.N.H.). Address reprint requests to Dr. Mehta at the Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, 101 The City Dr., Bldg. 23, Orange, CA 92868, or at rsmehta@uci.edu. Robert B. Livingston, M.D., is deceased.

 

参考文献

1. Mehta RS, Barlow WE, Albain KS, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med 2012;367:435-444.

2. Di Leo A, Jerusalem G, Petruzelka L, et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol 2010;28:4594-4600.

3. Bergh J, Jönsson PE, Lidbrink EK, et al. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol 2012;30:1919-1925.

4. Johnston SR, Kilburn LS, Ellis P, et al. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol 2013;14:989-998.

5. Di Leo A, Jerusalem G, Torres R, et al. First-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: a post-hoc analysis of the CONFIRM study. Breast 2018;38:144-149.

6. Ellis MJ, Llombart-Cussac A, Feltl D, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: overall survival analysis from the phase II FIRST study. J Clin Oncol 2015;33:3781-3787.

7. Robertson JFR, Bondarenko IM, Trishkina E, et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet 2016;388:2997-3005.

8. Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015;16:25-35.

9. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016;375:1738-1748.

10. Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med 2016;375:1925-1936.

11. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017;35:3638-3646.

12. Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol 2018;19:904-915.

13. Slamon DJ, Neven P, Chia S, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol 2018;36:2465-2472.

14. Dickler MN, Barry WT, Cirrincione CT, et al. Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance). J Clin Oncol 2016;34:2602-2609.

15. Martín M, Loibl S, von Minckwitz G, et al. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the Letrozole/Fulvestrant and Avastin (LEA) study. J Clin Oncol 2015;33:1045-1052.

16. Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med 2018;379:1926-1936.

服务条款 | 隐私政策 | 联系我们