Abstract
Ovarian cancer (OC) is associated with poor survival because there are a limited number of effective therapies. Two processes key to OC progression, angiogenesis and immune evasion, act synergistically to promote tumor progression. Tumor-associated angiogenesis promotes immune evasion, and tumor-related immune responses in the peritoneal cavity and tumor microenvironment (TME) affect neovascular formation. Therefore, suppressing the angiogenic pathways could facilitate the arrival of immune effector cells and reduce the presence of myeloid cells involved in immune suppression. To date, clinical studies have shown significant benefits with antiangiogenic therapy as first-line therapy in OC, as well as in recurrent disease, and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab is now an established therapy. Clinical data with immunomodulators in OC are more limited, but suggest that they could benefit some patients with recurrent disease. The preliminary results of two phase III trials have shown that the addition of immunomodulators to chemotherapy does not improve progression-free survival. For this reason, it could be interesting to look for synergistic effects between immunomodulators and other active drugs in OC. Since bevacizumab is approved for use in OC, and is tolerable when used in combination with immunotherapy in other indications, a number of clinical studies are underway to investigate the use of bevacizumab in combination with immunotherapeutic agents in OC. This strategy seeks to normalize the TME via the anti-VEGF actions of bevacizumab, while simultaneously stimulating the immune response via the immunotherapy. Results of these studies are awaited with interest.
Highlights
According to 2018 estimates, approximately 300,000 women around the world are diagnosed with ovarian cancer (OC) each year and approximately 185,000 women die from OC [1, 2]
Specific genomic patterns provide an opportunity for targeted therapy, such as inhibitors of poly ADP ribose polymerase (PARP) in patients with BRCA1/2 mutations [5], mainly high-grade serous carcinoma, or Ras/Raf/MEK/ERK inhibitors in patients with lowgrade serous carcinoma or mucinous ovarian carcinoma [4]
Preclinical data strongly suggest that antiangiogenic treatment facilitates the arrival of immune effectors and reduces the presence of myeloid cells involved in immune suppression, which could translate into a possible synergistic effect with immunomodulators [51]
Summary
According to 2018 estimates, approximately 300,000 women around the world are diagnosed with ovarian cancer (OC) each year and approximately 185,000 women die from OC [1, 2]. Preclinical data strongly suggest that antiangiogenic treatment facilitates the arrival of immune effectors and reduces the presence of myeloid cells involved in immune suppression, which could translate into a possible synergistic effect with immunomodulators [51] This has been demonstrated in a number of in vivo cancer models, including breast cancer, pancreatic neuroendocrine tumors, colon cancer, small-cell lung cancer, renal cell carcinoma, and melanoma whereby the administration of immunotherapy (cancer vaccine, adoptive cell therapy, a PD-1 or PD-L1 inhibitor, or a CTLA-4 inhibitor) and antiangiogenic agents showed more marked antitumor activity than the administration of either strategy alone [52, 53, 54, 55, 56, 57, 58, 59]. Clinical studies provide consistent evidence of durable responses with the combination of antiangiogenic therapy and immune checkpoint inhibitors in patients with in other tumor types, such as renal cell carcinoma (RCC) [63], non-small-cell lung cancer [64], or endometrial cancer [65]. II Platinum-resistant recurrent epithelial OC, primary peritoneal cancer and/or fallopian tube cancer
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