Division of Gynecologic Oncology, University of Alabama at Birmingham Hospital, South Birmingham, Alabama, USA.
Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Int J Gynecol Cancer. 2020 May;30(5):684-694. doi: 10.1136/ijgc-2019-001041. Epub 2020 Feb 19.
Most women with ovarian cancer experience disease relapse, presenting numerous treatment challenges for clinicians. Maintenance therapy in the relapsed setting aims to extend the time taken for a cancer to progress, thus delaying the need for additional treatments. Four therapies are currently approved in the USA for secondline maintenance treatment of platinum sensitive, recurrent ovarian cancer: one antivascular endothelial growth factor agent (bevacizumab) and three poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors (olaparib, niraparib, and rucaparib). In addition to efficacy, maintenance therapies must have a good tolerability profile and no significant detrimental impact on quality of life, as patients who receive maintenance are generally free from cancer related symptoms. Data from key bevacizumab trials (OCEANS, NCT00434642; GOG-0213, NCT00565851; MITO16B, NCT01802749) and PARP inhibitor trials (Study 19, NCT00753545; SOLO2, NCT01874353; NOVA, NCT01847274; ARIEL3, NCT01968213) indicate that bevacizumab and the PARP inhibitors are effective in patients with platinum sensitive, recurrent ovarian cancer but differ in their tolerability profiles. In addition, the efficacy of PARP inhibitors is dependent on the presence of homologous recombination repair deficiency, with patients with the deficiency experiencing greater responses from treatment compared with those who are homologous recombination repair proficient. Allowing for caveats of cross trial comparisons, we advise that clinicians account for the following points when choosing whether and when to administer a secondline maintenance treatment for a specific patient: presence of a homologous recombination repair deficient tumor; the patient's baseline characteristics, such as platelet count and blood pressure; mode of administration of therapy; and consideration of future treatment options for thirdline and later therapy.
大多数卵巢癌患者都会经历疾病复发，这给临床医生带来了诸多治疗挑战。复发后的维持治疗旨在延长癌症进展所需的时间，从而延缓额外治疗的需要。目前，美国有四种疗法被批准用于铂类敏感、复发性卵巢癌的二线维持治疗：一种抗血管内皮生长因子药物（贝伐珠单抗）和三种聚（腺苷二磷酸核糖）聚合酶（PARP）抑制剂（奥拉帕利、尼拉帕利和鲁卡帕利）。除了疗效外，维持治疗还必须具有良好的耐受性，且对生活质量没有显著的不利影响，因为接受维持治疗的患者通常没有癌症相关的症状。来自贝伐珠单抗关键试验（OCEANS，NCT00434642；GOG-0213，NCT00565851；MITO16B，NCT01802749）和 PARP 抑制剂试验（Study 19，NCT00753545；SOLO2，NCT01874353；NOVA，NCT01847274；ARIEL3，NCT01968213）的数据表明，贝伐珠单抗和 PARP 抑制剂对铂类敏感、复发性卵巢癌患者有效，但在耐受性方面存在差异。此外，PARP 抑制剂的疗效取决于同源重组修复缺陷的存在，与同源重组修复有效的患者相比，存在缺陷的患者对治疗的反应更大。考虑到交叉试验比较的注意事项，我们建议临床医生在为特定患者选择是否以及何时进行二线维持治疗时，考虑以下几点：肿瘤是否存在同源重组修复缺陷；患者的基线特征，如血小板计数和血压；治疗方式；以及对三线及以后治疗的未来治疗选择的考虑。
