Goh Jeffrey C H, Gourley Charlie, Tan David S P, Nogueira-Rodrigues Angélica, Elghazaly Hesham, Edy Pierre Marc, Giornelli Gonzalo, Kim Byoung-Gie, Morales-Vasquez Flavia, Tyulyandina Alexandra
Department of Oncology - Cancer Care Services, Level 5, Joyce Tweddell Building, Royal Brisbane & Women's Hospital, Butterfield Street, Herston, Queensland 4029, University of Queensland, St Lucia, Australia.
Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road South Edinburgh, EH4 2XR, UK.
Gynecol Oncol Rep. 2022 Jun 17;42:101028. doi: 10.1016/j.gore.2022.101028. eCollection 2022 Aug.
The incidence and mortality rates of ovarian cancer are increasing globally. Ovarian cancer is diagnosed at an advanced stage in 80% of women. After standard, platinum-based, front-line chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors and antiangiogenic agents are successfully employed as maintenance strategies for newly diagnosed, advanced ovarian cancer patients. Landmark clinical studies, including SOLO-1, PAOLA-1, PRIMA, and VELIA, have provided crucial insights on optimizing first-line maintenance treatment using PARP inhibitors. A group of ovarian cancer experts, primarily from low- and middle-income countries, met in September 2019 to discuss new developments for the first-line treatment of ovarian cancer and its implications. Key implications of the evolving clinical data included: (1) olaparib or niraparib maintenance therapy appears to be the preferred choice for patients with 1/2 mutations; hence, testing is beneficial in identifying these patients; (2) niraparib monotherapy and olaparib in combination with bevacizumab have demonstrated significant benefit in progression-free survival (PFS) in homologous recombination deficiency (HRD)-positive patients; (3) bevacizumab, niraparib alone, or observation can be an alternative for HRD-negative patients; (4) further data is warranted to explore the role of PARP inhibitors in treating HRD-negative, ovarian cancer patients to confirm findings of the exploratory analysis of PRIMA; (5) PARP inhibitors may be beneficial for stage IV ovarian cancer patients with inoperable disease and patients with prior neoadjuvant chemotherapy; and (6) there is an urgent need to increase awareness in both clinicians and patients on and HRD testing for optimizing treatment decision-making and improving clinical outcomes in newly diagnosed, advanced ovarian cancer patients. In clinical medicine, the limited availability of family history (FH) information and the complexity of FH criteria has hampered the implementation of BRCA testing. Moreover, many cancer patients with BRCA mutations are not tested because they do not meet the criteria for FH. Consequently, BRCA testing in many high income countries, including the US and Australia, is underused and used inappropriately, which has resulted in the loss of valuable opportunities for better cancer management and cancer prevention.
全球范围内，卵巢癌的发病率和死亡率都在上升。80%的女性在卵巢癌晚期才被确诊。在采用以铂类为基础的标准一线化疗后，聚（ADP - 核糖）聚合酶（PARP）抑制剂和抗血管生成药物被成功用作新诊断的晚期卵巢癌患者的维持治疗策略。包括SOLO - 1、PAOLA - 1、PRIMA和VELIA在内的里程碑式临床研究，为优化使用PARP抑制剂的一线维持治疗提供了关键见解。2019年9月，一群主要来自低收入和中等收入国家的卵巢癌专家齐聚一堂，讨论卵巢癌一线治疗的新进展及其影响。不断演变的临床数据的关键影响包括：（1）奥拉帕利或尼拉帕利维持治疗似乎是携带1/2种突变患者的首选；因此，进行检测有助于识别这些患者；（2）尼拉帕利单药治疗以及奥拉帕利与贝伐单抗联合使用，已在同源重组缺陷（HRD）阳性患者的无进展生存期（PFS）方面显示出显著益处；（3）对于HRD阴性患者，贝伐单抗、单独使用尼拉帕利或观察可以作为一种选择；（4）需要更多数据来探索PARP抑制剂在治疗HRD阴性卵巢癌患者中的作用，以证实PRIMA探索性分析的结果；（5）PARP抑制剂可能对患有无法手术疾病的IV期卵巢癌患者以及先前接受过新辅助化疗的患者有益；（6）迫切需要提高临床医生和患者对HRD检测的认识，以优化新诊断的晚期卵巢癌患者的治疗决策并改善临床结果。在临床医学中，家族史（FH）信息的有限可用性以及FH标准的复杂性阻碍了BRCA检测的实施。此外，许多携带BRCA突变的癌症患者未接受检测，因为他们不符合FH标准。因此，在美国和澳大利亚等许多高收入国家，BRCA检测未得到充分利用且使用不当，这导致失去了更好地管理癌症和预防癌症的宝贵机会。
