Gynecologic Cancer Program, University of Milan-Bicocca and European Institute of Oncology IRCCS, via Ripamonti 435, 20146 Milan, Italy.
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Ave, Toronto, ON, Canada.
Gynecol Oncol. 2020 Oct;159(1):101-111. doi: 10.1016/j.ygyno.2020.05.045. Epub 2020 Aug 26.
In the phase 3 trial ARIEL3, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib provided clinical benefit versus placebo for patients with recurrent, platinum-sensitive ovarian cancer. Here, we evaluate the impact of age on the clinical utility of rucaparib in ARIEL3.
Patients with platinum-sensitive, recurrent ovarian carcinoma with ≥2 prior platinum-based chemotherapies who responded to their last platinum-based therapy were enrolled in ARIEL3 and randomized 2:1 to rucaparib 600 mg twice daily or placebo. Exploratory, post hoc analyses of progression-free survival (PFS), patient-centered outcomes (quality-adjusted PFS [QA-PFS] and quality-adjusted time without symptoms or toxicity [Q-TWiST]), and safety were conducted in three age subgroups (<65 years, 65-74 years, and ≥75 years).
Investigator-assessed PFS was significantly longer with rucaparib than placebo in patients aged <65 years (rucaparib n = 237 vs placebo n = 117; median, 11.1 vs 5.4 months; hazard ratio [HR]: 0.33 [95% confidence interval (95% CI) 0.25-0.43]; P < 0.0001) and 65-74 years (n = 113 vs n = 64; median, 8.3 vs 5.3 months; HR 0.43 [95% CI 0.29-0.63]; P < 0.0001) and numerically longer in patients aged ≥75 years (n = 25 vs n = 8; median, 9.2 vs 5.5 months; HR 0.47 [95% CI 0.16-1.35]; P = 0.1593). QA-PFS and Q-TWiST were significantly longer with rucaparib than placebo across all age subgroups. Safety of rucaparib was generally similar across the age subgroups.
Efficacy, patient-centered outcomes, and safety of rucaparib were similar between age subgroups, indicating that all eligible women with recurrent ovarian cancer should be offered this therapeutic option, irrespective of age. https://clinicaltrials.gov/ct2/show/NCT01968213.
在 3 期 ARIEL3 试验中，聚（ADP-核糖）聚合酶（PARP）抑制剂芦卡帕尼作为维持治疗，为铂类敏感复发性卵巢癌患者提供了优于安慰剂的临床获益。在此，我们评估年龄对 ARIEL3 中芦卡帕尼临床应用的影响。
在 ARIEL3 中，入组了铂类敏感、复发的卵巢癌患者，这些患者在最后一次铂类化疗时曾有应答，并且在铂类化疗后复发，且接受过≥2 线铂类化疗。对无进展生存期（PFS）、患者为中心的结局（校正 PFS 质量调整后（QA-PFS）和无症状或毒性时间校正后质量调整后（Q-TWiST））以及安全性进行了探索性、事后分析，分为三个年龄亚组（<65 岁、65-74 岁和≥75 岁）。
在<65 岁（芦卡帕尼 n=237 例，安慰剂 n=117 例；中位 PFS，11.1 个月 vs 5.4 个月；风险比[HR]：0.33[95%置信区间（95%CI）0.25-0.43]；P<0.0001）和 65-74 岁（n=113 例，安慰剂 n=64 例；中位 PFS，8.3 个月 vs 5.3 个月；HR 0.43[95%CI 0.29-0.63]；P<0.0001）患者中，研究者评估的 PFS 显著长于安慰剂，在≥75 岁患者中也呈数值延长（n=25 例，安慰剂 n=8 例；中位 PFS，9.2 个月 vs 5.5 个月；HR 0.47[95%CI 0.16-1.35]；P=0.1593）。在所有年龄亚组中，QA-PFS 和 Q-TWiST 均显著长于安慰剂。在各年龄亚组中，芦卡帕尼的安全性大致相似。
在各年龄亚组中，芦卡帕尼的疗效、患者为中心的结局和安全性相似，这表明所有符合条件的复发性卵巢癌女性均应提供这种治疗选择，无论年龄大小。
