Promising first immunotherapy trial in placental trophoblastic tumours

Featured video: Avelumab in patients with gestational trophoblastic tumors resistant to monochemotherapy: Final outcomes of TROPHIMMUN phase II trial, cohort A.

 

Chemoresistant patients with a gestational trophoblastic tumour (GTT) responded well to avelumab in the TROPHIMMUN trial, presented by Prof. Benoit You (Lyon University Hospital, France). One patient went on to a normal pregnancy 1 year after treatment, in the first study of its kind in this rare tumour [1].

GTTs are rare tumours developing in the placenta during pregnancy, characterised by high human chorionic gonadotropin (hCG) blood levels. Low-risk patients with GTT receive a standard single-agent treatment (methotrexate or actinomycin-D) to achieve hCG normalisation, which can be obtained in 65-75% of patients. Patients who are chemoresistant to this approach typically receive polychemotherapy regimens, such as EMA-CO or BEP, with potential impact on future fertility [2].

In the current study, patients with GTT 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 normalising blood hCG levels. Over a period of 2 years, 17 patients were enrolled, and 15 patients were treated.

With a 27-month follow-up, normalisation 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. Reassuring for the impact of immunotherapy on fertility, a normal pregnancy occurred in 1 of the patients 1 year after successful treatment with avelumab.

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, diarrhoea), and there were no severe adverse events.

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

1. You B, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract LBA6008.
2. Seckl MJ, et al. Lancet. 2010;376(9742):717‐729.
3. Veras E, et al. Int J Gynecol Pathol. 2017;36(2):146‐153.

Posted on 9 September, 202022 February, 2024