The Ottawa Hospital Cancer Centre, Ottawa, Canada.
IOB Institute of Oncology, Quiron Group, Madrid & Barcelona, Spain; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Ann Oncol. 2021 Feb;32(2):197-207. doi: 10.1016/j.annonc.2020.10.596. Epub 2020 Nov 10.
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.
III 期 SANDPIPER 研究评估了 taselisib（GDC-0032），一种有效的、选择性的 PI3K 抑制剂，联合氟维司群，用于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。
绝经后患者在接受芳香酶抑制剂期间/之后疾病复发/进展，随机分为 2:1 组，接受 taselisib（4mg；taselisib 组）或安慰剂（安慰剂组）联合氟维司群（500mg）。分层因素为内脏疾病、内分泌敏感性和地理位置。有 PIK3CA 突变肿瘤的患者（中心 cobas® PIK3CA 突变检测）与无检测到突变的患者分开随机分组。主要终点是研究者评估的 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、总生存期、临床获益率、客观缓解持续时间、盲法独立中心审查（BICR-PFS）的无进展生存期、安全性和健康相关生活质量恶化时间。
PIK3CA 突变意向治疗人群包括 516 例患者（安慰剂组：n=176；taselisib 组：n=340）。与安慰剂组相比，taselisib 组的 INV-PFS 显著改善（7.4 个月[95%置信区间（CI）：7.26-9.07]）（分层风险比[HR]0.70；95%CI：0.56-0.89；P=0.0037），并通过 BICR-PFS 得到证实（HR0.66）。在 taselisib 组中，包括客观缓解率、临床获益率和客观缓解持续时间在内的次要终点均显示出一致的改善。安全性评估包括所有接受至少一剂 taselisib/安慰剂或氟维司群治疗的随机患者，无论 PIK3CA 突变状态如何（n=629）。安慰剂组的严重不良事件发生率低于 taselisib 组（8.9%比 32.0%）。安慰剂组的停药率（2.3%）和剂量减少率（2.3%）低于 taselisib 组。
SANDPIPER 达到了主要终点；然而，鉴于其安全性和适度的临床获益，taselisib 联合氟维司群的组合没有临床应用价值。
