In the French phase II TROPHIMMUN trial reported in the Journal of Clinical Oncology, Benoit You, MD, PhD, and colleagues found that avelumab normalized human chorionic gonadotropin (hCG) levels in approximately half of women with gestational trophoblastic tumors resistant to single-agent chemotherapy.
As stated by the investigators, “Women with gestational trophoblastic tumors resistant to single-agent chemotherapy receive alternative chemotherapy regimens, which, although effective, cause considerable toxicity. All gestational trophoblastic tumors subtypes express PD-L1, and natural killer cells are involved in trophoblast immunosurveillance. Avelumab (anti–PD-L1) induces natural killer cell–mediated cytotoxicity.”
Benoit You, MD, PhD
Study Details
In a cohort of the multicenter trial, 15 women whose disease progressed after single-agent chemotherapy were treated between December 2016 and September 2018 with 10 mg/kg of avelumab every 2 weeks until hCG normalization, followed by three consolidation cycles. The women had a median age of 34 years. Prior treatment included methotrexate (100%) and dactinomycin (7%). The primary endpoint was the rate of hCG normalization (cure).
hCG Normalization
Median follow-up was 25 months, and the median number of avelumab cycles was eight (range = 2–11). Normalization of hCG occurred in eight patients (53.3%) after a median of nine avelumab cycles, with no relapses observed among these patients.
Normalization of hCG occurred irrespective of disease stage, Federation of Gynecology and Obstetrics score, or baseline hCG level. One patient cured with 11 cycles of avelumab subsequently had a healthy pregnancy. Among the seven avelumab-resistant patients, hCG was subsequently normalized with dactinomycin in three, chemotherapy in three, and the combination of chemotherapy and hysterectomy in one.
KEY POINTS
- Normalization of hCG occurred in 8 of 15 patients receiving avelumab.
- No treatment-related grade ≥ 3 adverse events were observed.
Adverse Events
Treatment-related adverse events, all grade 1 or 2, occurred in 93% of patients, with the most commonly reported being fatigue (33.3%), nausea/vomiting (33.3%), and infusion-related reactions (26.7%). Serious adverse events occurred in two patients (13.3%), consisting of grade 2 ovarian cyst in one and grade 3 uterine bleeding in one, with both considered unrelated to treatment. Immune-related adverse events of any grade occurred in three patients, consisting of hyperthyroidism in two and hypothyroidism in one.
The investigators concluded: “In patients with single-agent chemotherapy-resistant gestational trophoblastic tumors, avelumab had a favorable safety profile and cured approximately 50% of patients. Avelumab could be a new therapeutic option, particularly in patients who would otherwise receive combination chemotherapy.”
Dr. You, of the Centre Hospitalier Lyon-Sud, Lyon Investigational Center for Treatments in Oncology and Hematology, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck KGaA, as part of an alliance between Merck KGaA and Pfizer. For full disclosures of the study authors, visit ascopubs.org.
