Avelumab Shows Modest Activity in Heavily Pretreated Ovarian Cancer, PD-L1 Status Explored
In the JAVELIN Solid Tumor phase 1b expansion, avelumab (anti-PD-L1) achieved a 9.6% objective response rate in 125 women with recurrent or refractory ovarian cancer who had received a median of three prior treatment lines. While responses were durable in select patients, the overall activity was modest. PD-L1 expression-based analyses were performed but did not clearly predict benefit, highlighting the need for better biomarker stratification in ovarian cancer immunotherapy.
The original study
Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial.
- Authors
- Disis ML, Taylor MH, Kelly K, Beck JT, Gordon M, Moore KM, et al.
- Journal
- JAMA oncology
- Type
- Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't
- PMID
- 30676622
Original abstract
IMPORTANCE: Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy. OBJECTIVE: To assess the efficacy and safety of avelumab, an anti-programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS: In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018. INTERVENTION: Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. MAIN OUTCOMES AND MEASURES: Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression-based analyses, and safety. RESULTS: A total of 125 women (median age, 62.0 years [range, 27-84 years]) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6%; 95% CI, 5.1%-16.2%), including a complete response in 1 patient (0.8%) and a partial response in 11 patients (8.8%). The 1-year progression-free survival rate was 10.2% (95% CI, 5.4%-16.7%) and median overall survival was 11.2 months (95% CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0%). Other frequent treatment-related adverse events (any grade event occurring in ≥10% of patients) were fatigue (17 [13.6%]), diarrhea (15 [12.0%]), and nausea (14 [11.2%]). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2%), of which only the level of lipase increased (3 [2.4%]) occurred in more than 1 patient. Twenty-one patients (16.8%) had an immune-related adverse event of any grade. No treatment-related deaths occurred. CONCLUSIONS AND RELEVANCE: Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01772004.