Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.
Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.
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DOI：
10.1007/s10549-017-4518-8
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发表时间：
2018-03
影响因子：
3.8
通讯作者：
Hortobagyi GN
中科院分区：
文献类型：
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作者：
O'Shaughnessy J;Petrakova K;Sonke GS;Conte P;Arteaga CL;Cameron DA;Hart LL;Villanueva C;Jakobsen E;Beck JT;Lindquist D;Souami F;Mondal S;Germa C;Hortobagyi GN
确定ribociclib联合来曲唑一线治疗原发晚期乳腺癌患者的疗效和安全性。III期MONALEESA-2试验（NCT 01958021）入组了HR+、HER 2 −晚期乳腺癌且既往未接受过晚期疾病全身治疗的绝经后女性。患者被随机分配至ribociclib（600 mg/天; 3周给药/1周停药）+来曲唑（2.5 mg/天;连续）或安慰剂+来曲唑组，直至疾病进展、不可接受的毒性、死亡或治疗中止。主要终点是评估者评估的无进展生存期;预定义的亚组分析评估了新发晚期乳腺癌患者的无进展生存期。次要终点包括安全性和总体缓解率。入组了668例患者，其中227例患者（34%; ribociclib+来曲唑vs安慰剂+来曲唑组：n = 114 vs. n = 113）患有新发晚期乳腺癌。在新发晚期乳腺癌患者中，ribociclib+来曲唑组未达到中位无进展生存期，而安慰剂+来曲唑组为16.4个月（风险比0.45，95%置信区间0.27-0.75）。最常见的3/4级不良事件为中性粒细胞减少症和白细胞减少症;发生率与整个MONALEESA-2人群中观察到的发生率相似。新发疾病患者中Ribociclib剂量中断和减量的发生频率与总体研究人群相似。Ribociclib联合来曲唑与安慰剂联合来曲唑相比，改善了无进展生存期，并且在HR+、HER 2 −新发晚期乳腺癌绝经后女性中耐受良好。
Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Postmenopausal women with HR+ , HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27–0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2− de novo advanced breast cancer.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
3.9
作者：
Cardoso, F.;Costa, A.;Winer, E.
通讯作者：
Winer, E.
DOI：
10.1093/annonc/mdw544
发表时间：
2017-01-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Cardoso F;Costa A;Senkus E;Aapro M;André F;Barrios CH;Bergh J;Bhattacharyya G;Biganzoli L;Cardoso MJ;Carey L;Corneliussen-James D;Curigliano G;Dieras V;El Saghir N;Eniu A;Fallowfield L;Fenech D;Francis P;Gelmon K;Gennari A;Harbeck N;Hudis C;Kaufman B;Krop I;Mayer M;Meijer H;Mertz S;Ohno S;Pagani O;Papadopoulos E;Peccatori F;Penault-Llorca F;Piccart MJ;Pierga JY;Rugo H;Shockney L;Sledge G;Swain S;Thomssen C;Tutt A;Vorobiof D;Xu B;Norton L;Winer E
通讯作者：
Winer E
影响因子：
3.9
作者：
Thangavel C;Dean JL;Ertel A;Knudsen KE;Aldaz CM;Witkiewicz AK;Clarke R;Knudsen ES
通讯作者：
Knudsen ES
影响因子：
168.9
作者：
Robertson, John F. R.;Bondarenko, Igor M.;Ellis, Matthew J.
通讯作者：
Ellis, Matthew J.