Department of Gynecological Oncology, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia.
Curr Treat Options Oncol. 2015 Jan;16(1):318. doi: 10.1007/s11864-014-0318-0.
In ovarian cancer (OC), the best established anti-angiogenic drug, bevacizumab, has demonstrated only modest prolonged progression free survival (PFS) and no increased overall survival (OS). The unanswered question is in which clinical situation bevacizumab might benefit ovarian cancer patients most. The cost-benefit analysis in the primary treatment was found not to be favorable but the use in the recurrent OC setting might be more compelling. Multi-targeted anti-angiogenic tyrosine kinase inhibitors (TKI) such as cediranib and pazopanib have shown some therapeutic benefits with improvements of PFS and OS in patients with platinum-sensitive as well as resistant OC, in whom there is a major need for novel therapies. Very promising is also the observed improvement of PFS in recurrent OC in patients when combining cediranib with the PARP inhibitor olaparib without giving additional chemotherapy. The anti-angiogenic agent trebananib has achieved similar results like TKI, but has a favorable toxicity profile which does not overlap with those of VEGF inhibitors. In cervical cancer the addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent or metastatic chemotherapy-naive disease results in a significant increase in OS. Considering the lack of therapeutic options in this difficult clinical setting, the inclusion of bevacizumab most likely will become a new standard for recurrent cervical cancer. In uterine sarcomas as very aggressive malignancies with a substantial need for better therapies the observed improved PFS with sorafenib warrants further investigation. No data showing a convincing improvement of survival in endometrial cancer have been presented yet. In view of the limited PFS and OS benefit observed with anti-angiogenics in gynecologic oncology, increased morbidity due to side effects of this treatment resulting in loss of quality of life and also substantial costs have to be taken into consideration. Thorough case selection based on molecular subgrouping of gynecologic cancers will therefore be a prerequisite for future anti-angiogenic therapy. This will require the integration of molecular diagnostics which still have to be developed and standardized.
在卵巢癌 (OC) 中，经过充分验证的抗血管生成药物贝伐珠单抗仅显示出适度的延长无进展生存期 (PFS)，并未增加总生存期 (OS)。目前尚未解决的问题是在何种临床情况下贝伐珠单抗最能使卵巢癌患者受益。初步治疗中的成本效益分析结果并不有利，但在复发性 OC 环境中的使用可能更具吸引力。多靶点抗血管生成酪氨酸激酶抑制剂（TKI），如西地尼布和帕唑帕尼，已显示出在铂敏感和耐药 OC 患者中具有一定的治疗益处，可改善 PFS 和 OS，而这些患者对新型疗法有很大需求。在复发性 OC 患者中，西地尼布联合 PARP 抑制剂奥拉帕利而不给予额外化疗，观察到 PFS 得到改善，这也非常有希望。抗血管生成剂替加尼布取得了与 TKI 类似的结果，但具有有利的毒性特征，与 VEGF 抑制剂无重叠。在复发性、持续性或转移性化疗初治疾病患者中，将贝伐珠单抗添加到联合化疗中，可显著增加 OS。鉴于在这种困难的临床环境中缺乏治疗选择，贝伐珠单抗的加入很可能成为复发性宫颈癌的新标准。在子宫肉瘤等非常侵袭性的恶性肿瘤中，索拉非尼观察到的 PFS 改善值得进一步研究。子宫内膜癌尚未提供令人信服的生存改善数据。鉴于抗血管生成药物在妇科肿瘤学中观察到的 PFS 和 OS 获益有限，由于这种治疗的副作用而导致的发病率增加，从而导致生活质量下降和大量费用，都需要考虑在内。因此，基于妇科癌症的分子亚组进行仔细的病例选择将是未来抗血管生成治疗的前提。这将需要整合分子诊断学，而这仍需要进一步开发和标准化。
