ASCO 2018: Dendritic Cell Vaccine

ASCO 2018

Dendritic cell vaccine improved progression-free survival when administered sequentially after chemotherapy. The vaccine provides a promising maintenance treatment option to delay progression of epithelial ovarian carcinoma.

This outcome of an interim analysis of a phase II, open-label, randomized, multicenter trial was reported at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, from June 1 – 5.

Lukas Rob, MD, PhD, of Charles University, Prague, Czech Republic, explained that most patients with epithelial ovarian cancer will relapse after primary debulking surgery and chemotherapy. Autologous dendritic cell vaccine can present tumor antigens to elicit a durable immune response.

Dr. Rob and colleagues hypothesized that adding the dendritic vaccine to chemotherapy would improve outcomes, including progression-free survival.

“Despite available treatment options,” Dr. Rob told Elsevier’s PracticeUpdate, “relapsed disease remains inevitable. Effective maintenance treatment options in the frontline setting are limited and represent an unmet medical need.”

“An innovative option,” he continued, “to prevent relapse is active cellular immunotherapy administered as maintenance treatment after adjuvant platinum-based chemotherapy.”

Key eligibility criteria were International Federation of Gynecology and Obstetrics stage 3 epithelial ovarian carcinoma (serous, endometrioid, or mucinous), performance status 0 – 2, post primary debulking surgery with <1 cm maximal residuum and no prior systemic therapy. Patients were randomized up to 6 weeks after primary debulking surgery, 1:1:1, into:

  • Arm A, n=34, dendritic cell vaccine + chemotherapy
  • Arm B, n=34, dendritic cell vaccine sequentially after chemotherapy
  • Arm C, n=31, chemotherapy alone

Patients were stratified by tumor residuum (0 or <1 cm). Chemotherapy consisted of 6 cycles of carboplatin (area under the curve 5 – 7) and paclitaxel (175 mg/m2 of body surface area). Patients in arms A and B were randomized to 10 doses of dendritic cell vaccine (1 × 107 dendritic cells per dose).

The primary endpoint was investigator-assessed progression-free survival. Key secondary endpoint was overall survival.

Between 2013 and 2016, 99 patients were randomized in 3 countries. Median age was comparable in all arms (range 61.5 – 62.0 years). The percentage of patients with complete cytoreduction was 85% in arms A and B, and 84% in arm C.

At the planned interim analysis, the intent-to-treat population included 31 patients in arm A, 30 patients in arm B, and 31 patients in arm C. Patients who failed leukapheresis or manufacturing were excluded.

A mean of 9.6 and 9.5 doses of dendritic cell vaccine were administered in arms A and B, respectively. Median follow-up duration was 26.8 (range 3.24 – 43.0) months. One patient withdrew informed consent early in the trial. Median progression-free survival was 18.3 months in arm A, 24.3 months in arm B, and 18.6 months in arm C.

Compared with arm C, hazard ratios for progression-free survival (95% confidence interval) were 1.08 (0.53 – 2.21) in arm A and 0.43 (0.18 – 1.03) in arm B. The gain in progression-free survival in the sequential arm was statistically significant (P = .05).

This improvement was supported by the same trend in overall survival. Median overall survival was not reached in any arm (14% events). No grade ≥3 adverse events related solely to dendritic cell therapy were observed.

“When we looked at baseline characteristics,” Dr. Rob noted, “they were well balanced across arms. In the frontline setting, the ability to prolong progression was clinically meaningful. Not only has the vaccine prolonged the time to progression, but patients are surviving longer based on the current hazard ratio (0.13; 95% confidence interval 0.02 – 1.08; P = .03). The results look very promising and if confirmed, the dendritic cell vaccine could be practice-changing.

The dendritic cell vaccine did not worsen the side effects of chemotherapy. The most common leukapheresis-related adverse events were mild pyrexia and moderate hypocalcemia.

Dr. Rob concluded that the dendritic cell vaccine improved progression-free survival when administered sequentially after chemotherapy. The vaccine provides a promising maintenance treatment option to delay progression of epithelial ovarian carcinoma.

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