The phase II trial evaluated dendritic cell–based immunotherapy with concomitant administration of chemotherapy vs chemotherapy alone.
Dendritic cell–based immunotherapy in combination with chemotherapy prolonged survival by longer than 1 year in women with recurrent ovarian cancer compared with chemotherapy alone, showed an open-label, randomized, multicenter, phase II trial presented at the 2019 Society of Gynecologic Oncology (SGO) 50th Annual Meeting on Women’s Cancer, held March 16–19 in Honolulu, Hawaii.
During an interview with Cancer Network, Robert Edwards, MD, Gynecologic Oncology Research, UPMC Magee-Womens Hospital, described the responses seen for the dendritic cell–based immunotherapy combination as “extremely dramatic.” He said, “Compared to incremental increases we’ve seen with cytotoxic therapy, this is a major leap forward.”
Between November 2013 and May 2015, the phase II trial (ClinicalTrials.gov identifier: NCT02107950) enrolled women from 15 centers in Europe with serous, endometrioid, or mucinous ovarian carcinoma that was platinum-sensitive. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 and at least one measurable lesion.
Patients were randomly assigned to treatment with either dendritic cell–based immunotherapy with concomitant administration of chemotherapy or chemotherapy alone, which is the standard of care. The chemotherapy regimen administered was carboplatin and gemcitabine for 6 to 10 cycles. For patients on the investigational arm, starting with the second cycle of chemotherapy, patients began receiving 5 induction doses of dendritic cell–based immunotherapy every 3 weeks, followed by 5 maintenance doses every 6 weeks.
The intention-to-treat analysis included 32 patients in each arm. At a median follow-up of 36.6 months, no significant difference in median progression-free survival (PFS) was found between treatment arms; patients on the dendritic cell–based immunotherapy plus chemotherapy arm had a median PFS of 11.3 months compared with 10.1 months for the chemotherapy-alone arm (hazard ratio [HR] = 0.77; 95% CI, 0.44–1.35; P = .35).
In contrast, the median overall survival (OS) was more than 1 year longer for patients on the dendritic cell–based immunotherapy plus chemotherapy arm compared with the chemotherapy-alone arm (35.5 vs 22.1 months; HR = 0.38; 95% CI, 0.20–0.74; P = .0032). At 2 years, 72.4% of those on the dendritic cell–based immunotherapy plus chemotherapy arm were still alive compared with 40.9% on the chemotherapy-alone arm.
Edwards explained that the lack of PFS benefit makes sense because the dendritic cell–based immunotherapy doesn’t add to the already high response rate seen with chemotherapy in this population of patients. As the tumors cell are dying from the chemotherapy, the immunotherapy induces an immune response and in essence creates a vaccination process in the patient. “That vaccination process leads to the long-term benefit of having more immune cells in the tumors when they eventually do recur, and so the patients live longer,” he explained.
Overall, Edwards said, he’s not surprised by the positive results of the trial. Involved in a comparable trial with a similar design, he said the findings are “completely consistent” with his group’s work in preclinical mouse models as well as in the clinic. He did find it “very encouraging” that this trial was done at multiple centers and was still able to show benefit.
A phase III trial to further evaluate dendritic cell–based immunotherapy in combination with chemotherapy for recurrent ovarian cancer is planned for 2019.