奧拉帕尼（Olaparib）是一種創新的、潛在首創口服多聚ADP核糖聚合酶(PARP)抑制劑， 在臨床前模型中已被證明， 能夠利用DNA修復途徑的缺陷， 優先殺死癌細胞。 這種作用模式， 賦予奧拉帕尼Olaparib治療具有DNA修復缺陷的廣泛腫瘤類型的潛力。 PARP與廣泛的腫瘤類型相關， 尤其是乳腺癌和卵巢癌。
《柳葉刀腫瘤分冊》2017年7月25日線上先發
http://thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30469-2/fulltext
奧拉帕尼片對BRCA1/2突變、鉑類敏感的復發性卵巢癌患者進行維持治療（SOLO2/ENGOT-Ov21試驗）：一項雙盲、隨機化、安慰劑對照的3期臨床試驗
背景
奧拉帕尼是一種多聚（ADP-核糖）聚合酶（PARP）抑制劑， 在既往的一項2期研究中， 對鉑類敏感、復發性、高級別的漿液性卵巢癌患者來者不拒地給予奧拉帕尼膠囊， 顯現出療效。 ， 我們旨在採用奧拉帕尼片劑， 在BRCA1或BRCA2（BRCA1/2）突變的患者中證實這些結果。
方法
這項國際性、多中心、雙盲、隨機化、安慰劑對照的3期臨床試驗， 對BRCA1/2突變、鉑類敏感的復發性卵巢癌患者，
結果
2013年9月3日至2014年11月21日， 我們入組了295名符合條件的患者， 這些患者隨機分組到奧拉帕尼組（n=196）或安慰劑組（n=99）。
解釋
在BRCA1/2突變、鉑類敏感、復發性卵巢癌患者中， 奧拉帕尼片維持治療使得無進展生存期明顯延長， 且對患者生活品質沒有產生有害影響。 除貧血以外， 奧拉帕尼的毒性低且可控。
Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial
Background
Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2) mutation using a tablet formulation of olaparib.
Methods
This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0–1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6–12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients.
Findings
Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3–25·7]) than with placebo (5·5 months [5·2–5·8]; hazard ratio [HR] 0·30 [95% CI 0·22–0·41], p
Interpretation
Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable.
Funding
AstraZeneca.
責任編輯：腫瘤資訊-Ruby