Promising first immunotherapy trial in placental trophoblastic tumors

Chemoresistant patients with a gestational trophoblastic tumor (GTT) responded well to avelumab, and 1 patient went on to a normal pregnancy 1 year after treatment, in the first study of its kind.

Chemo-resistant patients with a gestational trophoblastic tumor (GTT) responded well to avelumab, and 1 patient went on to a normal pregnancy 1 year after treatment, in the first study of its kind in this rare tumor.

Prof. Benoit You (Lyon University Hospital, France) presented the results of the TROPHIMMUN trial [1]. GTTs are rare tumors developing in the placenta during pregnancy, characterized by high human chorionic gonadotropin (hCG) blood levels. Low-risk patients with GTT receive single-agent treatment (methotrexate or actinomycin-D) to achieve hCG normalization, which can be obtained in 65-75% of patients. Patients who are chemo-resistant to this approach typically receive polychemotherapy regimens, such as EMA-CO or BEP, with a potential impact on future fertility [2].

In the current study, patients with GTT that are resistant to single-agent chemotherapy received avelumab every 2 weeks (Cohort A), based on the rationale that GTTs are known to express PD-L1 [3]. The objective of the trial was to assess the efficacy of avelumab in normalizing blood hCG levels.

Over a period of 2 years, 17 patients were enrolled, and 15 patients were treated. With a 27-month follow-up, normalization of hCG was achieved in 8 patients (53%), allowing avelumab discontinuation. No subsequent relapse was observed after discontinuation, suggesting durable responses. Resistance to avelumab was observed in the remaining 7 patients (47%), who were managed with chemotherapy with or without surgery. No patients died. A normal pregnancy occurred in 1 of the patients 1 year after successful treatment with avelumab, providing reassurance for the impact of immunotherapy on fertility.

No new safety events were reported, and no dose reduction or treatment delay was due to toxicity. Only mild or moderate adverse events were reported (fatigue, nausea, infusion-related reaction, dry eye, diarrhea), and there were no severe adverse events.

In conclusion, this first trial of immunotherapy demonstrated the feasibility of avelumab treatment in GTT patients resistant to single-agent chemotherapy. There is an ongoing phase 1-2 trial TROPHAMET, examining the safety and efficacy of methotrexate together with avelumab in the first-line setting.

Resources:
1. You, B et al. Avelumab in patients with gestational trophoblastic tumors resistant to monochemotherapy: Final outcomes of TROPHIMMUN phase II trial, cohort A. ASCO Virtual Meeting, 29-31 May 2020, Abstract LBA6008.
2. Seckl MJ, et al. Gestational trophoblastic disease. Lancet. 2010;376(9742):717‐729.
3. Veras E, et al. PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases. Int J Gynecol Pathol. 2017;36(2):146‐153.

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