Avelumab did not appear to be a suitable frontline treatment for patients with advanced epithelial ovarian cancer, according to findings from a phase 3 clinical trial.
“Generally more than 70% of women diagnosed with ovarian cancer have advanced disease,” Bradley J. Monk, MD, of the Department of Obstetrics and Gynecology at the University of Arizona College of Medicine, Phoenix, and colleagues wrote in The Lancet Oncology. “...Trials of immune checkpoint inhibitors as monotherapy in patients with previously treated epithelial ovarian cancer have shown modest clinical activity, prompting interest in the use of immune checkpoint inhibitors in combination with established treatments. Furthermore, accumulating evidence suggests that chemotherapy drugs might regulate antitumor immune responses.”
The researchers performed an open-label, three-arm, randomized controlled trial of 998 patients in 25 countries. Monk and colleagues randomly assigned patients with stage III or stage IV epithelial ovarian cancer at a 1:1:1 ratio to receive chemotherapy followed by maintenance with the immunotherapy drug avelumab (n = 332), chemotherapy plus avelumab followed by avelumab maintenance (n = 331 or chemotherapy followed by observation (control group; n = 335). The main outcome was progression-free survival (PFS).
At the time of the planned interim analysis, an independent review committee called a halt to the trial because it had passed “prespecified futility boundaries.” The median PFS was 16.8 months (95% CI, 13.5-not estimable [NE]) for patients assigned to chemotherapy and avelumab maintenance, the researchers reported, 18.1 months (95% CI, 14.8-NE) for the group assigned to combination therapy and not estimable for the control group (18.2 months-NE).
In the avelumab maintenance group, the stratified hazard ratio for PFS was 1.43 (95% CI, 1.05-1.95; one-sided P = 0·99) compared with the control group, whereas in the combination group, the HR was 1.14 (95% CI, 0.83-1·56; one-sided P = 0.79).
There were several common grade 3 or 4 adverse events: anemia (21% for the maintenance group, 19% for combination and 16% for controls), neutropenia (28% for maintenance, 30% for combination and 26% for controls) and decreased neutrophil count (15% for maintenance, 14% for combination and 18% for controls).
Slightly more than one-fourth (28%) of the maintenance group experienced serious adverse events of any grade, compared with 36% of the combination group and 19% of the control group.
Although researchers reported finding no new safety signals, they concluded avelumab was not an effective first-line treatment for these patients.
“In conclusion, the JAVELIN Ovarian 100 trial showed that avelumab as a maintenance therapy or in combination with chemotherapy did not improve progression-free survival compared with chemotherapy alone in patients with previously untreated epithelial ovarian cancer,” Monk and colleagues wrote.
Disclosures: Monk reports advising and consulting fees, as well as honoraria, from Agenus, Akeso, Aravive, AstraZeneca, Clovis Oncology, Eisai, Elevar Therapeutics, Genentech (subsidiary of Roche), Genmab and Seattle Genetics, GOG Foundation, Gradalis, ImmunoGen, Karyopharm Therapeutics, Iovance Biotherapeutics, Merck & Co, US Oncology Network (owned by McKesson), Mersana Therapeutics, Myriad Genetics, Novocure, Pfizer, Puma Biotechnology, Sorrento Therapeutics, Tesaro (owned by GlaxoSmithKline) and VBL Therapeutics. Please see the study for all authors’ disclosures.
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