Dendritic cell vaccine (DCVAC) with chemotherapy (ct) in patients (pts) with epithelial ovarian carcinoma (EOC) after primary debulking surgery (PDS): Interim analysis of a phase 2, open-label, randomized, multicenter trial.
ABSTRACT
Background: Most pts with EOC relapse after PDS and ct. Autologous DCVAC can present tumor antigens to elicit a durable immune response. We hypothesized that adding DCVAC to ct could improve outcomes, including progression-free survival (PFS).
Methods: Key eligibility criteria were FIGO stage III EOC (serous, endometrioid, or mucinous), PS 0 – 2, post-PDS with < 1cm maximal residuum and no prior systemic therapy. We randomized pts up to 6 weeks after PDS, 1:1:1, into arm A (A; DCVAC concomitantly with ct), arm B (B; DCVAC sequentially after ct) and arm C (C; ct alone). Pts were stratified by tumor residuum (0 or < 1cm). Ct consisted of 6 cycles of carboplatin (AUC 5 – 7) and paclitaxel (175mg/m2). Pts in A and B were to receive 10 doses of DCVAC (1 × 107 DCs/dose). The primary endpoint was investigator-assessed PFS. Key secondary endpoint was overall survival (OS).
Results: Between November 2013 and March 2016, 99 pts were randomized in 3 countries (A/B/C, 34/34/31). Median age was comparable in all arms (range, 61.5 – 62.0 years). The % of pts with complete cytoreduction was 85% in A and B, and 84% in C. At the planned interim analysis, the ITT population included 31 pts in A, 30 pts in B, and 31 pts in C; pts who failed leukapheresis (LP) or manufacturing were excluded. A mean of 9.6 and 9.5 doses of DCVAC were administered in A and B, respectively. Median follow-up time was 26.8 months (range, 3.24 – 43.0; 1 pt withdrew informed consent early in the trial). Median PFS was 18.3 months in A, 24.3 months in B, and 18.6 months in C. Compared to C, PFS hazard ratios (95% CI) were 1.08 (0.53 – 2.21) in A and 0.43 (0.18 – 1.03) in B. The gain in PFS in the sequential arm was statistically significant (p = 0.05), and this was supported by the same trend in OS. Median OS was not reached in any arm (14% events). There were no grade ≥ 3 adverse events (AEs) related solely to DCVAC and it did not worsen the side effects of ct. Most common LP-related AEs were mild pyrexia and moderate hypocalcemia.
Conclusions: DCVAC improved PFS when administered sequentially after ct. This provides a promising maintenance treatment option delaying progression of the disease. Clinical trial information: NCT02107937