In a French phase I/II trial (TROPHAMET) reported in JAMA Oncology, You et al found that first-line avelumab plus methotrexate was associated with high efficacy in patients with low-risk gestational trophoblastic tumors.
Study Details
In the multicenter study, 27 patients with low-risk gestational trophoblastic tumors (International Federation of Gynecology and Obstetrics [FIGO] score ≤ 6) enrolled between April 2020 and December 2023 received avelumab at 800 mg on day 1 plus intramuscular methotrexate at 1 mg/kg on days 1, 3, 5, and 7 alternating with oral folinic acid in 2-week cycles until normalization of human chorionic gonadotropin (hCG) level; patients then received three consolidation cycles. The phase II primary endpoint was the rate of serum hCG normalization that allowed treatment discontinuation.
Key Findings
The regimen showed acceptable safety in phase I. One patient experienced dose-limiting toxicity (grade 3 sepsis). Treatment-related adverse events of grade 2 or higher occurred in six patients (22%), with grade 3 mucositis and grade 3 liver toxicity occurring in two patients each; no grade 4 to 5 events were observed.
Among 26 patients evaluable for efficacy, 8 (31%) had FIGO scores of 1 to 2, 8 (31%) had scores of 3 to 4, and 10 (38%) had scores of 5 to 6. The rate of successful hCG normalization was 96.2% (90% confidence interval [CI] = 85.9%–97.9%).
No relapses were observed after a median follow-up of 41 months (interquartile range = 37–45 months).
Among 14 patients with childbearing potential and pregnancy intention, pregnancy was achieved in 13 (93%).
The investigators concluded: “In this nonrandomized clinical trial, avelumab combined with methotrexate demonstrated a manageable safety profile and high efficacy in low-risk [gestational trophoblastic tumors] in more than 95% of patients, with durable responses and preserved fertility. This combination may represent a promising first-line strategy warranting evaluation in comparative studies, particularly for patients at higher risk of chemoresistance.”
Benoit You, MD, PhD, of Centre Hospitalier Lyon–Sud, Centre d’Investigation de Thérapeutiques en Oncologie et Hématologie de Lyon, Lyon, France, is the corresponding author for the JAMA Oncology article.
DISCLOSURE: The study was funded by Merck KGaA. For full disclosures of the study authors, visit jamanetwork.com.
