Dendritic cell-based immunotherapy regimen extends OS in recurrent ovarian cancer
The addition of dendritic cell-based immunotherapy to chemotherapy significantly extended OS among women with platinum-sensitive, relapsed epithelial ovarian carcinoma, according to results of a randomized, phase 2 trial presented at Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
The immunotherapy regimen, however, did not significantly improve PFS compared with chemotherapy alone among these women.
“Dendritic cell-based immunotherapy may induce a delayed immunotherapeutic effect, and despite insignificant difference in PFS, it may still prolong OS,” David Cibula, MD, PhD, chair of Gynecologic Oncology Center at General University Hospital of Charles University in Prague, and colleagues wrote. “Therefore, we aimed to collect additional OS data and analyze long-term survival in this study.”
Cibula and colleagues enrolled 71 women with serous, endometrioid or mucinous ovarian carcinoma from 15 centers in Europe between November 2013 and May 2015. Eligibility criteria included ECOG performance status of 0 to 2, complete response after first-line platinum-based chemotherapy that endured for more than 6 months, and at least one measurable lesion according to RECIST version 1.1 criteria. Researchers excluded seven women who failed leukapheresis.
They randomly assigned the remaining women into one of two groups. Women in group A (n = 32; median age, 58.5 years) received a combination of carboplatin and gemcitabine for six to 10 cycles and, starting with the second chemotherapy cycle, five induction doses of dendritic cell-based chemotherapy every 3 weeks, followed by five maintenance doses every 6 weeks thereafter. Women in group B (median age, 60.5 years) received the chemotherapy regimen alone.
The groups had similar baseline characteristics. Researchers stratified the women based on previous use of bevacizumab (Avastin, Genentech) and length of remission (6-12 months or more than 12 months).
PFS served as the primary endpoint, with OS as the main secondary endpoint. The researchers planned the final cutoff when roughly 32 OS events had occurred.
At median follow-up of 36.6 months, 36 women had died.
The researchers observed no significant difference between group A and group B in median PFS (11.3 months vs. 10.1 months; HR = 0.77; 95% CI, 0.44-1.35).
However, survival curves revealed a significant difference in favor of the group receiving dendritic cell-based immunotherapy with chemotherapy (HR = 0.38; 95% CI, 0.2-0.74), This correlated with 2-year survival rates of 72.4% in group A and 40.9% in group B (difference, 31.5%; 95% CI, 5.3-57.7). Median OS was 35.5 months in group A vs. 22.1 months in group B.
“We hypothesize that the effect on OS but not PFS is due to the induction of long-lasting antitumor immunity by dendritic cell-based immunotherapy,” Cibula and colleagues wrote.
The immunotherapy regimen also had the major advantage of “an excellent safety profile and tolerance by patients, thanks to an almost absence of any toxicity,” Cibula said in a press release.
A larger, phase 3 study is planned for later in 2019.
“There are currently not many alternatives in clinical development with such promising results,” Cibula said in the release. – by Jennifer Byrne
Cibula D, et al. Abstract 35. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 16-19, 2019; Honolulu.
Disclosures: The study was sponsored by SOTIO. HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of reporting.