Women with advanced ovarian cancer who expressed the tumor antigen NY-ESO-1 demonstrated shorter PFS and OS than those without the antigen, according to study results published in Gynecologic Oncology.
However, patients with NY-ESO-1–expressing tumors who enrolled in immunotherapy trials had significantly improved OS, researchers reported.
“The most significant finding of the present study is we have identified a biomarker for aggressive ovarian cancer that is not only highly expressed, but is targetable with immunotherapy,” Kunle Odunsi, MD, PhD, FRCOG, deputy director and chair of the department of gynecologic oncology at Roswell Park, told HemOnc Today.
Ovarian cancer is the most lethal gynecological malignancy in the United States, accounting for about 14,000 deaths in 2016, and only incremental improvements have been made in survival rates. In their study, Odunsi and colleagues at Roswell Park aimed to provide an update on the prevalence of NY-ESO-1 expression in ovarian cancer, assess the association between NY-ESO-1 expression and clinical outcomes, and evaluate the survival impact of targeting NY-ESO-1 with immunotherapy.
From Jan. 1, 2002 to June 30, 2016, researchers tested 1,002 patients (median age, 61 years; 62.8% stage IIIc, 13.2% stage IV) for NY-ESO-1 expression.
Of these, 40.7% (n = 408) expressed NY-ESO-1. Women with NY-ESO-1 averaged 3 years older in age (62 years vs. 59 years; P < .001) and appeared more likely to have stage IIIc (62.7% vs. 52%) or stage IV (13.5% vs. 11%) disease.
NY-ESO-1 appeared associated with shorter PFS (22.2 months vs. 25 months; P = .009) and OS (42.9 months vs. 50 months; P = .002).
“NY-ESO-1 appears play a role in ovarian cancer similar to HER-2/neu in breast cancer, where overexpression is associated with a worse prognosis, until trastuzumab (Herceptin, Genentech) became available, and now those patients have improved outcomes,” Odunsi said. “Therefore, we encourage ovarian cancer patients to have their tumors tested for NY-ESO-1.”
Researchers offered 11 immunotherapy vaccine trials to the 408 women who tested positive for NY-ESO-1; 68 patients accepted. Women who enrolled tended to be younger (54.5 years vs. 64 years; P = .002) and had similar stage, grade and histology of disease.
Women who received immunotherapy had longer OS (75.3 months) than women who did not enroll (38 months; P < .001) and women without NY-ESO-1 expression (50 months; P = .046).
“The patients received various forms of NY-ESO-1–targeted vaccine therapies,” J. Brian Szender, MD, MPH, fellow in the department of gynecologic oncology at Roswell Park Cancer Institute, told HemOnc Today. “Our vaccine therapy approaches are focused on ovarian cancer patients in remission or with minimal residual disease burden in order to minimize the risk for relapse. For patients with large-volume disease, we have developed adoptive T-cell therapies using engineered T cells that are programed to bear T-cell receptors that recognize NY-ESO-1 in tumors.”
Researchers encourage patients with NY-ESO-1 expression to participate in vaccine clinical trials to reduce their risk for relapse.
“For patients with recurrent or progressive ovarian cancer who have failed more than two lines of standard chemotherapies, we encourage participation in clinical trials of adoptive T-cell therapy targeting NY-ESO-1,” Odunsi said. “Because NY-ESO-1 is not expressed by all patients, we have developed a clinical trial where NY-ESO-1 expression is enforced pharmacologically, followed by adoptive T-cell therapy with TCR–engineered cells targeting NY-ESO-1.”
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