What question did this study set out to answer?

This research aims to compare the efficacy of avelumab plus methotrexate versus methotrexate alone in treating low-risk gestational trophoblastic neoplasia.

March 12, 2026Open Access

31MO Comparing efficacy of avelumab + methotrexate vs. methotrexate alone in low-risk gestational trophoblastic neoplasia: A national registry-based external control comparison

Puntos clave

This research aims to compare the efficacy of avelumab plus methotrexate versus methotrexate alone in treating low-risk gestational trophoblastic neoplasia.
Performed an external control comparison using a national registry of GTN patients with a FIGO score of 6.
Analyzed data from patients treated between 2020 and 2025 at the French Reference Center for Trophoblastic Diseases.
Main outcome measured was serum hCG normalization, allowing for treatment discontinuation.
Used G-computation and bootstrap methods for statistical analysis.
The probability of hCG normalization for patients treated with methotrexate plus avelumab was 96.6%.
Observed risk ratio for hCG normalization was 1.21 (95% CI, 1.06 to 1.39).
Risk difference was 0.17 (95% CI, 0.05 to 0.28).
Sensitivity analyses produced consistent results.

Resumen

Background: Low-risk gestational trophoblastic neoplasia (GTN) affects young women.The standard "8-day methotrexate" (MTX) regimen achieves a 70-80% cure rate as first-line treatment, but resistance may require second-line chemotherapy, delaying fertility and causing toxicity.The TROPHAMET single-arm phase I/II trial showed that combining avelumab (AVE) with MTX achieved a 96.2% success rate.Methods: To compare these first-line strategies before a potential phase III trial, we designed an external control comparison in the target trial framework using data from GTN patients with a FIGO (International Federation of Gynecology and Obstetrics) score 6 treated between 2020 and 2025 and prospectively registered to the French Reference Center for Trophoblastic Diseases (FRCTD).The main outcome was serum human chorionic gonadotropin (hCG) normalization allowing treatment discontinuation.G-computation was performed to compare results between MTX + AVE and MTX alone, using the FIGO score as the main confounding factor.The 95% confidence intervals (CI) for risk ratio and risk difference estimates were constructed using a percentile-based bootstrap CI with 10,000 bootstrap samples.Several sensitivity analyses were performed.Results: Among the 276 eligible patients in the FRCTD database (mean age, 35 years, 268 post molar GTN 97%, 44 FIGO score 5-6 16%, 104 FIGO stage III 38%), 29 received the experimental treatment MTX + AVE (i.e., the single-arm group) and 247 received the control treatment MTX (i.e., the external control group).In the patients treated with MTX + AVE, the observed probability of hCG normalization was 96.6%.Risk ratio was 1.21 (95%CI, 1.06 to 1.39) and risk difference was 0.17 (95%CI, 0.05 to 0.28).Sensitivity analyses showed consistent results. Conclusions:This study shows that, for low-risk GTN patients, a first-line treatment of MTX+AVE leads to a higher rate of hCG normalization than MTX alone.These findings reinforce the suggestions of the TROPHAMET clinical trial and encourage the conduct of a phase III trial.

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