Avelumab Shows Early Promise For Treatment-Resistant Gestational Trophoblastic Tumours

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Women with gestational trophoblastic tumours (GTT) resistant to single-agent chemotherapy may benefit from avelumab treatment, the TROPHIMMUN investigators say.

“TROPHIMMUN is a proof-of-concept trial showing that immunotherapy with avelumab could potentially cure approximately 50% of patients with GTT who have resistance to single-agent chemotherapy while avoiding the toxic effects of chemotherapy, expanding treatment options in this disease”, the researchers write in the Journal of Clinical Oncology.

The phase II open-label study included 15 patients, aged a median 34 years, with progressive disease after methotrexate, and in one case treatment with actinomycin D. The patients had stage I (53.3%) or stage III (46.7%) disease and FIGO scores of 0–4 (33.3%), 5–6 (46.7%) or at least 7 (20.0%).

After a median nine cycles of avelumab 10 mg/kg at 2-week intervals, the primary endpoint of human chorionic gonadotropin (hCG) normalisation was achieved by eight of the patients, one of whom had a response after treatment discontinuation.

None of these patients experienced relapse over a median follow-up of 29 months, “meaning they are likely to be cured”, the investigators say, noting that five of these patients would otherwise have required combination chemotherapy.

Among the seven patients who did not achieve hCG normalisation after a median 4.5 cycles, 42.3% were successfully treated with actinomycin D, 42.3% with combination chemotherapy, and one (14.3%) underwent hysterectomy, report Benoit You, from the Lyon Investigational Center for Treatments in Oncology and Hematology in France, and co-authors.

Safety analysis identified treatment-related adverse events in 93.3% of patients but all were at grade 1 or 2. These included fatigue (33.3%), nausea or vomiting (33.3%) and infusion-related reactions (26.7%), as well as immune-related hyperthyroidism (13.3%) and hypothyroidism (6.7%).

One patient who was successfully treated with avelumab went on to a healthy pregnancy, which the researchers say provides “reassurance about the lack of impact on fertility in this patient population, which includes many women of child-bearing potential.”

Acknowledging the study’s small size and lack of comparator treatment arm, Benoit You et al write that further research is required to identify “potential predictive markers, long-term safety, efficacy, and cost effectiveness” of avelumab therapy.

The second cohort of the TROPHIMMUN study will assess avelumab in patients whose GTT is resistant to combination therapy, they say, while the TROPHAMET study is investigating the combination of avelumab and methotrexate as a first-line therapy for GTT.

Reference

You B, Bolze P-A, Lotz J-P, et al. Avelumab in patients with gestational trophoblastic tumors with resistance to single-agent chemotherapy: Cohort A of the TROPHIMMUN phase II trial. J Clin Oncol; Advance online publication 27 July 2020. DOI:10.1200/JCO.20.00803