Dendritic Cell-Based Immunotherapy Plus Second-Line Chemotherapy Shows Significant OS Increase for Patients with Ovarian Cancer

Combining dendritic cell-based immunotherapy (DCVAC/OvCa) with second-line chemotherapy in patients with platinum-sensitive ovarian cancer did not improve progression-free survival (PFS) but did prolong overall survival (OS), according to data from Gynecologic Oncology.¹

In an open-label phase 2 trial (NCT02107950) 71 patients with platinum-sensitive ovarian cancer who relapsed after first-line chemotherapy were randomized to either 10 doses of DCVAC/OvCa every 3-6 weeks plus chemotherapy or chemotherapy alone. PFS was not found to be improved (HR 0.73; 95% CI 0.42–1.28, P = 0.27), but median OS was significantly prolonged by 13.4 months in the DCVAC/OvCa and chemotherapy group (HR 0.38, 95% CI 0.20–0.74, P = 0.003).

PFS was the primary efficacy end point of the study along with secondary end points of OS, biological progression-free interval (PFIBIO), objective response rate (ORR), and immune responses.

Median PFS in the treatment arm was 11.3 months compared to 9.5 months in the chemotherapy alone arm, moreover, PFIBIO was not significantly greater in the DCVAC/OvCa at 10.3 months compared to 10.1 months (HR 0.82; 95% CI 0.47–1.43, P = 0.478) in the control group. The OS was initially not significant at the time of analysis with a median OS of 23.8 months in the DCVAC/OvCa group vs 21.5 months in the control group (HR 0.63, 95% CI: 0.26–1.54, P = 0.30), but these data were immature at the time according to the researchers.

An exploratory analysis, conducted through May 2018, showed an OS increase by 13.4 months in the DCVAC/OvCa group from 29.5 months to 35.5 months of OS. Furthermore, for the 14 of 20 patients withdrawn from the trial the median OS was 7.3 months longer in the DCVAC/OvCa group at 29.5 versus 22.2 months in the chemotherapy arm.

ORR was also greater in the DCVAC/OvCa group at 87.5% (95% CI, 71%–96.5%) compared with the control group at 62.5% (95% CI, 43.7%–78.9%). Risk reduction for death was also 62% in the treatment group compared to chemotherapy alone.

“The reason why DCVAC/OvCa prolonged OS, but not PFS, is not fully clear,” the researchers wrote in their analysis of the study results. “We hypothesize that DCVAC/OvCa induces a delayed, yet durable anticancer immune response that leads to long-term disease stabilization and slower progression, resulting in prolonged survival.”

In both groups, similar proportions of patients experienced treatment-emergent adverse events (TEAEs) from the chemotherapy, however, grade 3 or greater TEAEs were experienced in patients in the control group than the treatment group at 78.4% versus 83.9%, respectively. The most common grade 3 or greater TEAEs were thrombocytopenia (64.9% vs 80.6%), anemia (64.9% vs 67.7%), neutropenia (59.5% vs 67.75), and leukopenia (45.9% vs 32.3%).

All these TEAES occurred in 10 or more patients among each group, and most of these events were related to chemotherapy, according to the researchers. TEAEs reported to be only related to treatment with DCVAC/OvCa were abdominal rigidity, injection site erythema, and lymphadenopathy. Two patients in the treatment arm had TEAEs which led to death compared to none in the chemotherapy group, while only 1 patient had TEAEs that led to trial withdrawal due to chemotherapy.

“DCVAC/OvCa did not improve PFS, but exploratory analyses showed it may have prolonged OS and enhanced surrogate antigen-specific T-cell activity,” the researchers concluded. “These findings warrant confirmation in appropriately powered randomized studies.”

_Reference

_{Cibula D, Rob L, Mallmann P, et al. Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial. Gynecol Oncol. 2021 Sep;162(3):652-660. doi: 10.1016/j.ygyno.2021.07.003}