第3轮POLO研究表明，在转移性胰腺癌和生殖系BRCA突变患者中，使用奥拉帕尼进行积极维护治疗与安慰剂相比，可以显著延长无进展生存期(PFS)并保持健康相关生命质量(HRQOL)。在这里，我们提供了一项基于患者中心结果的事后分析：没有疾病进展或毒性症状的时间(TWiST)和质量调整TWiST(Q-TWiST)。患者被随机分配到维护奥拉帕尼(300毫克片剂，每日两次)或安慰剂，比例为3:2。总生存时间分为TWiST、毒性(TOX；疾病进展前有显著毒性症状的时间)和复发(REL；疾病进展后至死亡或截尾的时间)。Q-TWiST是TWiST、TOX和REL之和，每个周期的健康状态期间通过HRQOL效用分数加权。采用不同的TOX定义进行基本情况和三个敏感度分析。总共随机到154名患者(奥拉帕尼组n=92；安慰剂组n=62)。在基本情况和所有敏感度分析中，奥拉帕尼组的TWiST明显长于安慰剂组(14.6比7.1个月；95% CI，2.9-12.0；p=0.001)。在基本情况和敏感度分析中，Q-TWiST没有明显的益处(18.4比15.9个月；95% CI，-1.1至6.1；p=0.171)。这些结果支持以前的研究发现，维护奥拉帕尼相对于安慰剂显著改善PFS而不损害HRQOL，并证明即使考虑毒性症状，奥拉帕尼的临床意义的益处仍然存在。 ©2023年美国癌症协会。

The phase 3 POLO study demonstrated a significant progression-free survival (PFS) benefit and preserved health-related quality of life (HRQOL) for active maintenance treatment with olaparib vs placebo in patients with metastatic pancreatic cancer and a germline BRCA mutation. Here, we present a post hoc analysis of the patient-centered outcomes: time without significant symptoms of disease progression or toxicity (TWiST) and quality-adjusted TWiST (Q-TWiST).Patients were randomized 3:2 to maintenance olaparib (300 mg tablets twice daily) or placebo. Overall survival time was divided into TWiST, toxicity (TOX; time before disease progression with significant symptoms of toxicity), and relapse (REL; time after disease progression until death or censoring). Q-TWiST was the sum of TWiST, TOX, and REL, each weighted by HRQOL utility scores during the relevant health-state period. A base-case and three sensitivity analyses were performed using differing definitions of TOX.In total, 154 patients were randomized (olaparib, n = 92; placebo, n = 62). TWiST was significantly longer for olaparib than placebo in the base-case analysis (14.6 vs 7.1 months; 95% CI, 2.9-12.0; p = .001) and all sensitivity analyses. No statistically significant benefit for Q-TWiST was observed in the base-case analysis (18.4 vs 15.9 months; 95% CI, -1.1 to 6.1; p = .171) or the sensitivity analyses.These results support the previous findings that maintenance olaparib significantly improves PFS relative to placebo without compromising HRQOL and demonstrate that the clinically meaningful benefits of olaparib persist even when symptoms of toxicity are considered.© 2023 American Cancer Society.