Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial.
Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial.
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在雌激素受体阳性、PIK3CA突变、HER2阴性的晚期乳腺癌中，他塞西布或安慰剂与富维斯特联合治疗的第三阶段随机研究：Sandpiper试验。
DOI：
10.1016/j.annonc.2020.10.596
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Jacot W
中科院分区：
文献类型：
--
作者：
Dent S;Cortés J;Im YH;Diéras V;Harbeck N;Krop IE;Wilson TR;Cui N;Schimmoller F;Hsu JY;He J;De Laurentiis M;Sousa S;Drullinsky P;Jacot W
Sandpiper的第三阶段研究评估了Taselisib(GDC-0032)，一种有效的、选择性的PI3K抑制剂，加上氟维斯特治疗雌激素受体阳性、HER2阴性、PIK3CA突变的局部晚期或转移性乳腺癌。在服用芳香酶抑制剂期间/之后，有疾病复发/进展的绝经后妇女被随机分为两组，分别接受taselisib(4毫克；taselisib组)或安慰剂(安慰剂组)加氟维司特(500 Mg)治疗。分层因素包括内脏疾病、内分泌敏感性和地理区域。有PIK3CA突变的肿瘤患者(中央眼镜蛇PIK3CA突变测试)与未检测到突变的患者被随机分开。主要终点是研究人员评估的PIK3CA突变肿瘤患者的无进展生存期(INV-PFS)。次要终点包括客观缓解率、总存活率、临床受益率、客观缓解期、BICR-PFS(BICR-PFS)、安全性和与健康相关的生活质量恶化时间。PIK3CA突变意向治疗人群包括516名患者(安慰剂组：176例；taselisib组：340例)。与安慰剂组(5.4月[95%可信区间，3.68-7.29])(分层危险比[HR]0.70；95%可信区间，0.56-0.89；P=0.0037)相比，Taselisib组的INV-PFS显著改善(95%可信区间，7.26-9.07)，BICR-PFS(HR0.66)证实。次要终点，包括客观应答率、临床受益率和客观应答期，在taselisib臂中显示出持续的改善。安全性评估是在所有随机接受至少一剂他赛西布/安慰剂或弗维斯特的患者中进行的，与PIK3CA突变状态无关(n=629)。服用安慰剂的患者严重不良反应发生率低于服用他赛西布的患者(8.9%比32.0%)。在taselisib组中有更多的停药(安慰剂组：2.3%；taselisib组：16.8%)和剂量减少(安慰剂组：2.3%；taselisib组：36.5%)。Sandpiper达到了其主要终点；然而，考虑到其安全性和适度的临床益处，taselisib和fulvestrant的组合没有临床实用价值。
The phase III SANDPIPER study assessed taselisib (GDC-0032), a potent, selective PI3K inhibitor, plus fulvestrant in estrogen receptor-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer. Postmenopausal women with disease recurrence/progression during/after an aromatase inhibitor were randomized 2 : 1 to receive taselisib (4 mg; taselisib arm) or placebo (placebo arm) plus fulvestrant (500 mg). Stratification factors were visceral disease, endocrine sensitivity, and geographic region. Patients with PIK3CA-mutant tumors (central cobas® PIK3CA Mutation Test) were randomized separately from those without detectable mutations. The primary endpoint was investigator-assessed progression-free survival (INV-PFS) in patients with PIK3CA-mutant tumors. Secondary endpoints included objective response rate, overall survival, clinical benefit rate, duration of objective response, PFS by blinded independent central review (BICR-PFS), safety, and time to deterioration in health-related quality of life. The PIK3CA-mutant intention-to-treat population comprised 516 patients (placebo arm: n = 176; taselisib arm: n = 340). INV-PFS was significantly improved in the taselisib {7.4 months [95% confidence interval (CI), 7.26-9.07]} versus placebo arm (5.4 months [95% CI, 3.68-7.29]) (stratified hazard ratio [HR] 0.70; 95% CI, 0.56-0.89; P = 0.0037) and confirmed by BICR-PFS (HR 0.66). Secondary endpoints, including objective response rate, clinical benefit rate, and duration of objective response, showed consistent improvements in the taselisib arm. Safety was assessed in all randomized patients who received at least one dose of taselisib/placebo or fulvestrant regardless of PIK3CA-mutation status (n = 629). Serious adverse events were lower in the placebo versus taselisib arm (8.9% versus 32.0%). There were more discontinuations (placebo arm: 2.3%; taselisib arm: 16.8%) and dose reductions (placebo arm: 2.3%; taselisib arm: 36.5%) in the taselisib arm. SANDPIPER met its primary endpoint; however, the combination of taselisib plus fulvestrant has no clinical utility given its safety profile and modest clinical benefit.
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DOI：
10.1158/1078-0432.ccr-14-0947
发表时间：
2015-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
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通讯作者：
de Bono JS
影响因子：
28.2
作者：
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DOI：
10.1016/s1470-2045(17)30376-5
发表时间：
2017-07
期刊：
The Lancet. Oncology
影响因子：
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作者：
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通讯作者：
Campone M
DOI：
10.1126/science.aah6893
发表时间：
2017-03-24
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Toska E;Osmanbeyoglu HU;Castel P;Chan C;Hendrickson RC;Elkabets M;Dickler MN;Scaltriti M;Leslie CS;Armstrong SA;Baselga J
通讯作者：
Baselga J
影响因子：
3.8
作者：
Arthur, L. M.;Turnbull, A. K.;Dixon, J. M.
通讯作者：
Dixon, J. M.