Avelumab in patients with gestational trophoblastic tumors with resistance to polychemotherapy: Cohort B of the TROPHIMMUN phase 2 trial

ElsevierVolume 168, January 2023, Pages 62-67Gynecologic OncologyHighlights•

In patients with gestational trophoblastic tumor resistant to polychemotherapy, single agent avelumab had limited activity

The prognosis of patients with gestational trophoblastic tumors resistant to polychemotherapy is unfavorable

In this population, there is a need for immunotherapy-based innovative combinations

AbstractPurpose

There is a need for innovative treatments in women with gestational trophoblastic tumors (GTT) resistant to chemotherapy. The TROPHIMMUN trial assessed the efficacy of avelumab in patients with resistance to single-agent chemotherapy (cohort A), or to polychemotherapy (cohort B). Cohort B outcomes are reported here.

Methods

In the cohort B of this phase 2 multicenter trial (NCT03135769), women with GTT progressing after polychemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. The primary endpoint was the rate of hCG normalization enabling treatment discontinuation (2-stage Simon design).

Results

Between February 2017 and August 2020, 7 patients were enrolled. Median age was 37 years (range: 29–47); disease stage was I or III in 42.9% and 57.1%; FIGO score was 9–10 in 28.6%, 11 in 28.6%, and 16 in 14.3%, respectively. Median follow-up was 18.2 months. One patient (14.3%) experienced hCG normalization enabling treatment discontinuation. However, resistance to avelumab was observed in the remaining 6 patients (85.7%). The cohort B was stopped for futility. Grade 1–2 treatment-related adverse events occurred in 57.1%, most commonly fatigue (42.9%), nausea, diarrhea, infusion-related reaction, muscle pains, dry eyes (each 14.3%). The median resistance-free survival was 1.4 months (95% CI 0.7–5.3).

Conclusions

Although avelumab is active in patients with single-agent chemotherapy-resistant GTT (cohort A), it was associated with limited efficacy in patients with resistance to polychemotherapy (cohort B). The prognosis of patients with polychemotherapy resistance remains poor, and innovative immunotherapy-based therapeutic combinations are needed.

Keywords

Gestational trophoblastic disease

Antibodies

Monoclonal

Drug resistance

Neoplasm

Immunotherapy

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