Chambers Laura M, O'Malley David M, Coleman Robert L, Herzog Thomas J
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The James Cancer Hospital and Solove Research Institute, The Ohio State University Medical Center, Columbus, OH.
US Oncology Research, The Woodlands, TX.
Am J Obstet Gynecol. 2022 Nov;227(5):728-734. doi: 10.1016/j.ajog.2022.05.047. Epub 2022 May 28.
Ovarian cancer is the leading cause of gynecologic cancer-related death in the United States. Historically, studies have demonstrated that ovarian cancer is a heterogeneous disease with several patient and oncologic characteristics, including BRCA status and residual disease at surgery, known to be predictive of clinical outcomes. However, during the last decade, the discovery and approval of bevacizumab and poly(adenosine diphosphate-ribose) polymerase inhibitors have moved the frontline treatment paradigm beyond platinum-doublet therapy for women with advanced ovarian cancer. Subsequently, investigators have sought to assess the therapeutic efficacy of these agents in women who are considered "high" risk and "low" risk to determine which patients may benefit the most from aggressive therapy and in whom additional treatment may be avoided. We reviewed historic and contemporary definitions of "high-risk" and "low-risk" ovarian cancer and how this has been incorporated into the subset analyses of randomized, clinical trials of therapeutic agents, including bevacizumab and poly(adenosine diphosphate-ribose) polymerase inhibitors. Next, we provided an in-depth discussion of landmark trials for frontline maintenance therapy with bevacizumab and/or poly(adenosine diphosphate-ribose) polymerase inhibitors, focusing on the impact of treatment efficacy according to a "high-risk" and "low-risk" paradigm. Furthermore, we highlighted that recent data have challenged this dichotomous classification, notably from the Gynecologic Oncology Group-0218, ICON7, SOLO-1, and PAOLA-1 trials. Although some studies have suggested that certain populations of women with advanced ovarian cancer may have a more favorable prognosis and be considered "low risk," the risk of progression and death remains unacceptably high in all women. Furthermore, in many cases, those considered the lowest risk have the most treatment benefit from maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors and/or bevacizumab. From these data, we have advocated that virtually all women with advanced ovarian cancer are high risk and that the use of our most effective therapies in the frontline setting holds promise for potentially curing more patients. Lastly, we critically discuss the practice of using subanalyses in clinical trials, with emphasis that although this practice is important for hypothesis generation, caution must be taken before accepting findings from subanalyses as actual treatment effects.
卵巢癌是美国妇科癌症相关死亡的主要原因。从历史上看，研究表明卵巢癌是一种异质性疾病，具有多种患者和肿瘤学特征，包括BRCA状态和手术时的残留疾病，已知这些特征可预测临床结果。然而，在过去十年中，贝伐单抗和聚（腺苷二磷酸 - 核糖）聚合酶抑制剂的发现和批准，使晚期卵巢癌女性的一线治疗模式超越了铂类双联疗法。随后，研究人员试图评估这些药物在被认为“高”风险和“低”风险女性中的治疗效果，以确定哪些患者可能从积极治疗中获益最大，以及哪些患者可以避免额外治疗。我们回顾了“高风险”和“低风险”卵巢癌的历史和当代定义，以及这是如何纳入治疗药物（包括贝伐单抗和聚（腺苷二磷酸 - 核糖）聚合酶抑制剂）随机临床试验的亚组分析中的。接下来，我们深入讨论了贝伐单抗和/或聚（腺苷二磷酸 - 核糖）聚合酶抑制剂一线维持治疗的标志性试验，重点关注根据“高风险”和“低风险”模式的治疗效果影响。此外，我们强调最近的数据对这种二分法分类提出了挑战，特别是来自妇科肿瘤学组 - 0218、ICON7、SOLO - 1和PAOLA - 1试验的数据。尽管一些研究表明，某些晚期卵巢癌女性群体可能预后较好，被认为是“低风险”，但所有女性的进展和死亡风险仍然高得令人无法接受。此外，在许多情况下，那些被认为风险最低的女性从聚（腺苷二磷酸 - 核糖）聚合酶抑制剂和/或贝伐单抗维持治疗中获得的治疗益处最大。根据这些数据，我们主张几乎所有晚期卵巢癌女性都是高风险的，并且在一线治疗中使用我们最有效的疗法有望治愈更多患者。最后，我们批判性地讨论了在临床试验中使用亚组分析的做法，强调虽然这种做法对于提出假设很重要，但在将亚组分析的结果作为实际治疗效果接受之前必须谨慎。
