Survival Predictors in Ovarian Cancer and Current Immunotherapeutic Strategies
Researchers have found 3 major predictors for survival: tumor infiltrating leukocytes (TIL), programmed death-ligand 1 (PD-L1) expression, and mutational burden.
|The following article features coverage from the Chemotherapy Foundation Symposium (CFS) in New York, NY. Click here to read more of Cancer Therapy Advisor's conference coverage.|
The evidence for immune checkpoint inhibitors as treatment for patients with ovarian cancer is growing, with several studies demonstrating durable and complete tumor regression in chemotherapy-refractory disease, according to an oral presentation given at the 35th Annual Chemotherapy Foundation Symposium in New York.1
Bradley J. Monk, MD, FACS, FACOG, discussed several immunotherapeutic approaches currently being explored and utilized for the treatment of ovarian cancer. Researchers have identified 3 major predictors for survival, which include tumor infiltrating leukocytes (TIL), programmed death-ligand 1 (PD-L1) expression, and mutational burden.
Although the presence of TILs at time of newly diagnosed ovarian cancer was found to be the most important prognostic factor for improved survival (hazard ratio [HR], 2.24; 95% CI, 1.71-2.92), in a prior study only 55% of tumor samples had TILs. PD-L1 expression is another major prognostic factor, but it is only identified in approximately 68% of patients. High levels of PD-L1 expression in ovarian cancer not only lead to poorer overall survival (OS) outcomes, but negatively affect progression-free survival (PFS) as well. Mutational burden is typically low in ovarian cancer.
Monotherapy with anti-PD-1 agents, such as nivolumab and pembrolizumab, only result in a 10% to 15% response rate among patients with ovarian cancer. One of the treatment challenges with checkpoint inhibitors for patients with ovarian cancer moving forward is increasing the amount of TILs, and thus immunogenicity, in tumor cells.
Previous studies have demonstrated that chemotherapy is immunogenic and enhances antigen presentation, immunogenicity, and increases cell susceptibility to immune attack. Pegylated liposomal doxorubicin (PLD) and carboplatin plus paclitaxel have demonstrated clinical efficacy in animal studies.
PARP inhibitors (PARPi) (eg, olaparib, rucaparib, niraparib) cause genomic instability and increase immunogenicity through an increase in mutational burden, neoantigens, and eventual PD-L1 expression and increased TIL. Researchers believe that combing PARPi and checkpoint inhibitor combinations may have a synergistic effect.
Moving forward, Dr Monk stressed that the identification of appropriate biomarkers is a crucial step. He concluded “Microsatellite instability and BRCA status are promising biomarkers, but further investigation in ovarian cancer is needed.”
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- Monk BJ. Elucidating a role for immunotherapy in ovarian cancer. Oral presentation at: 35th Annual Chemotherapy Foundation Symposium. November 8-10, 2017; New York, NY.