Medical University of Gdańsk, Gdańsk, Poland.
Institut Gustave Roussy, Villejuif, France.
Int J Cancer. 2023 Aug 15;153(4):803-814. doi: 10.1002/ijc.34525. Epub 2023 Apr 6.
In the primary analysis of the phase III OlympiAD trial, olaparib significantly prolonged progression-free survival (PFS) vs chemotherapy treatment of physician's choice (TPC) in patients with germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer (mBC). We report subgroup analyses for the final analysis at a median OS follow-up of 18.9 months (olaparib) and 15.5 months (TPC). Patients (N = 302) with gBRCAm, HER2-negative mBC and ≤2 previous lines of chemotherapy for mBC were randomized 2:1 to open-label olaparib (300 mg twice daily) or TPC. All subgroup analyses were prespecified except site of metastases. Investigator-assessed median PFS was 8.0 months (95% confidence interval [CI] 5.8-8.4; 176/205 events) for olaparib and 3.8 months (95% CI 2.8-4.2; 83/97 events) for TPC (hazard ratio 0.51, 95% CI 0.39-0.66). In subgroup analyses, median PFS hazard ratios (95% CI) favored olaparib: hormone receptor status (triple-negative: 0.47, 0.32-0.69; hormone receptor-positive: 0.52, 0.36-0.75); gBRCAm (BRCA1: 0.49, 0.35-0.71; BRCA2: 0.49, 0.33-0.74); site of metastases (visceral/CNS: 0.53, 0.40-0.71; non-visceral: 0.45, 0.23-0.98); prior chemotherapy for mBC (yes: 0.51, 0.38-0.70; no: 0.49, 0.30-0.82); prior platinum-based chemotherapy for BC (yes: 0.49, 0.30-0.83; no: 0.50, 0.37-0.69); progressive disease at randomization (yes: 0.48, 0.35-0.65; no: 0.61, 0.36-1.07). Investigator-assessed objective response rates were higher across all subgroups with olaparib (35-68%) vs TPC (5-40%). Global health status/health-related quality of life increased in all subgroups with olaparib vs decreased/no change with TPC. These data confirm the consistency of olaparib benefit across patient subgroups in OlympiAD.
在 OlympiAD 试验的 III 期主要分析中，奥拉帕利与医生选择的化疗（TPC）相比，显著延长了种系 BRCA 突变（gBRCAm）、HER2 阴性转移性乳腺癌（mBC）患者的无进展生存期（PFS）。我们报告了在中位 OS 随访 18.9 个月（奥拉帕利）和 15.5 个月（TPC）时最终分析的亚组分析。gBRCAm、HER2 阴性 mBC 和 mBC 既往接受 ≤2 线化疗的患者按 2:1 随机分配接受奥拉帕利（300mg 每日两次）或 TPC。除转移部位外，所有亚组分析均为预设。研究者评估的中位 PFS 为奥拉帕利组 8.0 个月（95%置信区间[CI] 5.8-8.4；176/205 例事件）和 TPC 组 3.8 个月（95%CI 2.8-4.2；83/97 例事件）（风险比 0.51，95%CI 0.39-0.66）。在亚组分析中，中位 PFS 风险比（95%CI）有利于奥拉帕利：激素受体状态（三阴性：0.47，0.32-0.69；激素受体阳性：0.52，0.36-0.75）；gBRCAm（BRCA1：0.49，0.35-0.71；BRCA2：0.49，0.33-0.74）；转移部位（内脏/CNS：0.53，0.40-0.71；非内脏：0.45，0.23-0.98）；mBC 的既往化疗（是：0.51，0.38-0.70；否：0.49，0.30-0.82）；BC 的既往铂类化疗（是：0.49，0.30-0.83；否：0.50，0.37-0.69）；随机时疾病进展（是：0.48，0.35-0.65；否：0.61，0.36-1.07）。奥拉帕利组的客观缓解率高于所有亚组（35-68%），而 TPC 组的客观缓解率为 5-40%。奥拉帕利组所有亚组的全球健康状况/健康相关生活质量均增加，而 TPC 组则下降或无变化。这些数据证实了奥拉帕利在 OlympiAD 中的获益在各患者亚组中的一致性。
