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新诊断晚期卵巢癌患者的奥拉帕利维持治疗
Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer


Kathleen Moore ... 肿瘤 妇产科和儿科 • 2018.12.27
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• 尼拉帕尼用于铂类敏感型复发性卵巢癌的维持治疗 • 卵巢癌的腹腔热灌注化疗

复发率极高的晚期卵巢癌的维持治疗有了新武器

 

杨佳欣,沈铿*

北京协和医院肿瘤妇科中心

*通讯作者

 

卵巢上皮性癌(简称卵巢癌)是病死率最高的妇科恶性肿瘤。因为缺乏早期诊断方法,卵巢癌的临床现状不佳,其可用两个70%形容——70%以上确诊时为Ⅲc以上的晚期卵巢癌,70%以上晚期卵巢癌在初次治疗后的3年内复发。晚期卵巢癌5年生存率一直徘徊在30%~40%。

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摘要


背景

大多数新诊断的晚期卵巢癌患者在标准治疗(手术+铂类化疗)后3年内复发。复发患者口服聚腺苷二磷酸核糖聚合酶抑制剂奥拉帕利的获益已经得到充分证实,但奥拉帕利作为维持治疗用于新诊断卵巢癌的获益尚未确定。

 

方法

我们开展了一项国际性、随机、双盲、3期试验,在铂类化疗后完全或部分临床缓解,有BRCA1BRCA2或同时有BRCA1/2突变的新诊断晚期(国际妇产科联合会[International Federation of Gynecology and Obstetrics]分期Ⅲ期或Ⅳ期)高级别浆液性或子宫内膜样卵巢癌、原发性腹膜癌或输卵管癌(或这些癌症的组合)患者中,评估了奥拉帕利维持治疗的疗效。以2∶1的比例将患者随机分组,接受奥拉帕利片剂(每日2次、每次300 mg)或安慰剂治疗。主要终点为无进展生存期。

 

结果

在被随机分组的391例患者中,260例被分配接受奥拉帕利治疗,131例被分配接受安慰剂治疗。共有388例患者存在得到集中证实的生殖细胞BRCA1/2突变,2例患者存在得到集中证实的体细胞BRCA1/2突变。中位随访41个月之后,奥拉帕利组的疾病进展或死亡风险比安慰剂组低70%(3年时无疾病进展并且无死亡比率的Kaplan-Meier估计值,60% vs. 27%;疾病进展或死亡的风险比,0.30;95%置信区间,0.23~0.41;P<0.001)。不良事件与奥拉帕利的已知毒性作用一致。

 

结论

在有BRCA 1/2突变的新诊断晚期卵巢癌患者中,奥拉帕利维持治疗在无进展生存期方面有显著获益,奥拉帕利组的疾病进展或死亡风险比安慰剂组低70%(由阿斯利康和默克资助;SOLO 1在ClinicalTrials.gov注册号为NCT01844986)。





作者信息

Kathleen Moore, M.D., Nicoletta Colombo, M.D., Giovanni Scambia, M.D., Byoung-Gie Kim, M.D., Ph.D., Ana Oaknin, M.D., Ph.D., Michael Friedlander, M.D., Alla Lisyanskaya, M.D., Anne Floquet, M.D., Alexandra Leary, M.D., Gabe S. Sonke, M.D., Ph.D., Charlie Gourley, M.D., Ph.D., Susana Banerjee, M.D., Ph.D., Amit Oza, M.D., Antonio González-Martín, M.D., Ph.D., Carol Aghajanian, M.D., William Bradley, M.D., Cara Mathews, M.D., Joyce Liu, M.D., Elizabeth S. Lowe, M.D., Ralph Bloomfield, M.Sc., and Paul DiSilvestro, M.D.
From the Stephenson Cancer Center at the University of Oklahoma, Oklahoma City (K.M.); University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Milan (N.C.), and Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica, Rome (G.S.) — both in Italy; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (B.-G.K.); Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona (A. Oaknin), and M.D. Anderson Cancer Centre Madrid, Madrid (A.G.-M.) — both in Spain; University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, Australia (M.F.); St. Petersburg City Oncology Dispensary, St. Petersburg, Russia (A. Lisyanskaya); Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens, Paris (A.F., A. Leary), Institut Bergonié, Comprehensive Cancer Center, Bordeaux (A.F.), and Gustave-Roussy Cancer Campus, Villejuif (A. Leary) — all in France; the Netherlands Cancer Institute, Amsterdam (G.S.S.); Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (C.G.), the Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London (S.B.), and AstraZeneca, Cambridge (R.B.) — all in the United Kingdom; Princess Margaret Cancer Centre, Toronto (A. Oza); Memorial Sloan Kettering Cancer Center, New York (C.A.); Froedtert and the Medical College of Wisconsin, Milwaukee (W.B.); Women and Infants Hospital, Providence, RI (C.M., P.D.); Dana–Farber Cancer Institute, Boston (J.L.); and AstraZeneca, Gaithersburg, MD (E.S.L.). Address reprint requests to Dr. Moore at the Stephenson Cancer Center at the University of Oklahoma, 800 NE 10th St., Oklahoma City, OK 73104, or at kathleen-moore@ouhsc.edu.

 

参考文献

1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: ovarian cancer version 2. 2018 (https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf).

2. Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24:Suppl 6:vi24-vi32.

3. Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011;365:2473-2483.

4. Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011;365:2484-2496.

5. Burger RA, Enserro D, Tewari KS, et al. Final overall survival (OS) analysis of an international randomized trial evaluating bevacizumab (BEV) in the primary treatment of advanced ovarian cancer: a NRG oncology/Gynecologic Oncology Group (GOG) study. J Clin Oncol 2018;36:5517-5517. abstract.

6. O’Connor MJ. Targeting the DNA damage response in cancer. Mol Cell 2015;60:547-560.

7. AstraZeneca. Lynparza (olaparib) tablets, for oral use: prescribing information. 2018 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s001lbl.pdf).

8. AstraZeneca. Global policy: bioethics. 2016 (https://www.astrazeneca.com/content/dam/az/PDF/2016/Bioethics_policy.pdf).

9. Norquist BM, Brady MF, Harrell MI, et al. Mutations in homologous recombination genes and outcomes in ovarian carcinoma patients in GOG 218: an NRG Oncology/Gynecologic Oncology Group study. Clin Cancer Res 2018;24:777-783.

10. Alsop K, Fereday S, Meldrum C, et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 2012;30:2654-2663.

11. Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:1949-1961.

12. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 2016;375:2154-2164.

13. Pujade-Lauraine E, Ledermann JA, Selle F, et al. 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. Lancet Oncol 2017;18:1274-1284.

14. Gourley C, Friedlander M, Matulonis UA, et al. Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC). J Clin Oncol 2017;35:5533-5533. abstract.

15. Ledermann JA, Harter P, Gourley C, et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol 2016;17:1579-1589.

16. Osoba D, Bezjak A, Brundage M, Zee B, Tu D, Pater J. Analysis and interpretation of health-related quality-of-life data from clinical trials: basic approach of the National Cancer Institute of Canada Clinical Trials Group. Eur J Cancer 2005;41:280-287.

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