The phase II study was the first trial to explore the use of immunotherapy for patients who were resistant to standard chemotherapy treatment
Treatment with avelumab (Bavencio) prevented relapse in women with gestational trophoblastic tumors (GTT) that were resistant to single-agent chemotherapy, according to results of a study presented during the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.
The small phase II study, which is the first trial to explore the use of immunotherapy in patients with GTT, found that 53% of patients responded to therapy, suggesting that avelumab may be a new therapeutic option for these patients.1
"This proof-of-concept study shows that treatment with the immunotherapy avelumab works against these tumors when resistance to single-agent chemotherapy develops,” said lead author Benoit You, MD, PhD, of the Centre Hospitalier Lyon-Sud and Lyon Investigational Center for Treatments in Oncology and Hematology in France in a press release.2 “Although more evidence is needed before changing clinical practice, these are highly promising results, suggesting that avelumab could prevent patients with chemo-resistant disease from the severe toxicity of chemotherapy combinations.”
The trial enrolled 17 patients over 2 years. Of those, 15 patients were treatable and assessable. Successful normalization of human chorionic gonadotropin (hCG) was seen in 53% (n = 8) of patients, leading to discontinuation of avelumab. There was no sign of disease relapse in any of the patients after 29 months of follow up. Researchers consider patients who reach 12 months disease free with no relapse to be cured.
Intravenous avelumab was given at 10â mg/kg every 2 weeks to patients with GTT who were resistant to monochemotherapy (cohort A) or to polychemotherapy (cohort B). Avelumab was administered until hCG normalization, and for 3 additional cycles thereafter. The primary endpoint was measured as the rate of patients with hCG normalization, following a 2 step Simon design.
Resistance to avelumab was noted in the remaining 47% (n = 7) of patients. Those patients were managed with chemotherapy, either with or without surgery.
One patient who experienced hCG normalization from avelumab treatment developed a normal pregnancy and delivered a healthy baby 1 year after treatment discontinuation. “This is the first report of a normal pregnancy in a patient previously cured from her tumor with immunotherapy,” said You in a prerecorded press briefing.2 “This provides reassuring data about the impact of immunotherapy on subsequent fertility.”
The investigators reported a satisfactory safety profile for avelumab, with no severe adverse events (AEs) reported. Ninety-three percent of patients developed drug-related grade 1-2 AEs (grade 1, 86%), with the most common including fatigue (33%) and nausea-vomiting (33%). Infusion-related reactions (27%), thyroid disorder (20%), dry eyes (20%), and diarrhea (20%) were also reported. A grade 3 uterus bleeding was observed in 1 patient; however, this was unrelated to treatment. Median follow-up was 30 months.
GTTs are rare, abnormal growths in the uterus that develop from the placenta during conception and show an overexpression of programmed death-ligand 1 (PD-L1) proteins. Avelumab inhibits PD-L1, making it a reasonable alternative to chemotherapy for patients with these tumors.
The researchers are currently conducting a similar trial for avelumab in the first-line setting, treating low-risk tumors with methotrexate and avelumab before resistance can develop. “The objective is to cure 95% of patients,” You said during a presscast. “With methotrexate, we estimate that we can cure 70% of patients. What we expect is that with the combination with avelumab, we will be able to cure 95% of patients.”