Domchek Susan M, Aghajanian Carol, Shapira-Frommer Ronnie, Schmutzler Rita K, Audeh M William, Friedlander Michael, Balmaña Judith, Mitchell Gillian, Fried Georgeta, Stemmer Salomon M, Hubert Ayala, Rosengarten Ora, Loman Niklas, Robertson Jane D, Mann Helen, Kaufman Bella
Basser Research Center and Abramson Cancer Center, Philadelphia, PA, USA.
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Gynecol Oncol. 2016 Feb;140(2):199-203. doi: 10.1016/j.ygyno.2015.12.020. Epub 2015 Dec 23.
The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.govNCT01078662) have been reported previously.
Eligible patients were treated with oral olaparib 400mg bid capsule monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for patients with measurable disease at baseline. Safety and tolerability were assessed for all patients by adverse event (AE) incidence and changes in laboratory parameters. Platinum resistance status was obtained retrospectively, and responses to olaparib evaluated.
In patients with gBRCA1/2m ovarian cancer, 154/193 (80%) had received ≥3 prior lines of chemotherapy, of whom 137/154 (89%) had measurable disease at baseline. ORR was 34% (46/137; 95% confidence interval [CI] 26-42) and median DoR was 7.9 (95% CI 5.6-9.6) months. ORR in platinum-resistant tumors was 30%. Median DoR for platinum-sensitive and platinum-resistant disease was similar: 8.2months (95% CI 5.6-13.5) compared with 8.0months (4.8-14.8), respectively. Six of the 193 (3%) patients had an AE with an outcome of death. None of these AEs at time of occurrence was considered causally related to olaparib.
Following ≥3 prior lines of chemotherapy, olaparib 400mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified.
在接受过≥3线先前化疗的种系BRCA1/2突变（gBRCA1/2m）晚期卵巢癌患者亚组中，研究口服聚（ADP-核糖）聚合酶（PARP）抑制剂奥拉帕利的疗效和安全性。该II期研究（研究42，ClinicalTrials.govNCT01078662）的主要数据此前已报道。
符合条件的患者接受口服奥拉帕利400mg每日两次胶囊单药治疗，直至根据RECIST v1.1出现疾病进展。对基线时可测量疾病的患者评估客观缓解率（ORR）和缓解持续时间（DoR）。通过不良事件（AE）发生率和实验室参数变化评估所有患者的安全性和耐受性。回顾性获取铂耐药状态，并评估对奥拉帕利的反应。
在gBRCA1/2m卵巢癌患者中，154/193（80%）接受过≥3线先前化疗，其中137/154（89%）在基线时有可测量疾病。ORR为34%（46/137；95%置信区间[CI]26 - 42），中位DoR为7.9（95%CI 5.6 - 9.6）个月。铂耐药肿瘤的ORR为30%。铂敏感和铂耐药疾病的中位DoR相似：分别为8.2个月（95%CI 5.6 - 13.5）和8.0个月（4.8 - 14.8）。193例患者中有6例（3%）出现AE且结局为死亡。这些AE在发生时均未被认为与奥拉帕利有因果关系。
在接受≥3线先前化疗后，奥拉帕利400mg每日两次（胶囊剂型）单药治疗在gBRCA1/2m晚期卵巢癌患者中显示出显著的抗肿瘤活性。未发现新的安全信号。
