As reported by Bradley J. Monk, MD, and colleagues in The Lancet Oncology, the phase III JAVELIN Ovarian 100 trial showed no progression-free survival benefit with the addition of concurrent and/or maintenance avelumab to chemotherapy in previously untreated patients with advanced epithelial ovarian cancer. The fully enrolled trial was stopped for futility at a planned interim analysis.
Bradley J. Monk, MD
Study Details
In the open-label trial, 998 patients with stage III or IV disease from sites in 25 countries were randomly assigned 1:1:1 between May 2016 and January 2018 to receive chemotherapy with carboplatin/paclitaxel followed by avelumab maintenance (avelumab maintenance group, n = 332), chemotherapy plus avelumab followed by avelumab maintenance (avelumab combination group, n = 331), or chemotherapy alone (control group, n = 335).
Chemotherapy consisted of six cycles of carboplatin at AUC 5 or 6 every 3 weeks, plus investigator’s choice of paclitaxel at 175 mg/m² every 3 weeks or 80 mg/m² once a week. Avelumab was given in combination with chemotherapy at 10 mg/kg every 3 weeks and as maintenance at 10 mg/kg every 2 weeks.
The primary endpoint was progression-free survival as assessed by blinded independent central review in the intention-to-treat population.
Progression-Free Survival
At the planned interim analysis (data cutoff in September 2018), prespecified futility boundaries were crossed for the progression-free survival analysis, and the trial was stopped based on the recommendation of the independent data monitoring committee.
Median follow-up for progression-free survival was 11.1 months for the avelumab maintenance group, 11.0 months for the avelumab combination group, and 10.2 months for the control group. Median progression-free survival was 16.8 months (95% confidence interval [CI] = 13.5 months–not estimable) in the avelumab maintenance group, 18.1 months (95% CI = 14.8 months–not estimable) in the avelumab combination group, and not reached (95% CI = 18.2 months–not estimable) in the control group. Compared with the control group, stratified hazard ratios were 1.43 (95% CI = 1.05–1.95, P = .99) for the avelumab maintenance group and 1.14 (95% CI = 0.83–1.56, P = .79) for the avelumab combination group.
Assessment of maintenance phase progression-free survival among 248 patients in the avelumab maintenance group, 267 in the avelumab combination group, and 247 in the control group without disease progression during the chemotherapy phase showed median durations of 13.6 months, 13.8 months, and not reached, respectively. Compared with the control group, stratified hazard ratios were 1.56 (95% CI = 1.08–2.27, P = .99) in the avelumab maintenance group and 1.26 (95% CI = 0.86–1.85, P = .89) in the avelumab combination group.
Overall survival data were not mature at the time of the interim analysis. Death had occurred in 6% of patients in the avelumab maintenance group, 6% of the avelumab combination group, and 4% of the control group at time of analysis.
KEY POINTS
- The trial was stopped for futility after preplanned interim analysis.
- Neither the addition of avelumab to chemotherapy plus avelumab maintenance nor avelumab maintenance after chemotherapy improved progression-free survival vs chemotherapy alone.
Adverse Events
The most common grade 3 and 4 adverse events were anemia (21% in avelumab maintenance group, 19% in avelumab combination group, and 16% in control group), neutropenia (28%, 30%, and 6%), and decreased neutrophil count (15%, 14%, and 18%). Serious adverse events occurred in 28%, 36%, and 19% of patients, respectively. Death considered related to treatment occurred in one patient in the avelumab maintenance group (due to atrial fibrillation) and one patient in the avelumab combination group (due to disease progression).
The investigators concluded, “Although no new safety signals were observed, results do not support the use of avelumab in the front-line treatment setting. Alternative treatment regimens are needed to improve outcomes in patients with advanced epithelial ovarian cancer.”
Dr. Monk, of Arizona Oncology (The US Oncology Network), Phoenix, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Pfizer and Merck KGaA. For full disclosures of the study authors, visit thelancet.com.
