Avelumab in Patients With Gestational Trophoblastic Tumors With Resistance to Single-Agent Chemotherapy: Cohort A of the TROPHIMMUN Phase II Trial

J Clin Oncol. 2020 Sep 20;38(27):3129-3137. doi: 10.1200/JCO.20.00803. Epub 2020 Jul 27.

Abstract

Purpose: Women with gestational trophoblastic tumors (GTT) resistant to single-agent chemotherapy receive alternative chemotherapy regimens, which, although effective, cause considerable toxicity. All GTT subtypes express programmed death-ligand 1 (PD-L1), and natural killer (NK) cells are involved in trophoblast immunosurveillance. Avelumab (anti-PD-L1) induces NK cell-mediated cytotoxicity. The TROPHIMMUN trial assessed avelumab in women with chemotherapy-resistant GTT.

Methods: In this phase II multicenter trial (ClinicalTrials.gov identifier: NCT03135769), women with GTT who experienced disease progression after single-agent chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. Rate of hCG normalization was the primary endpoint (2-step Simon design).

Results: Between December 2016 and September 2018, 15 patients were treated. Median age was 34 years; disease stage was I or III in 53.3% and 46.7% of women, respectively; and International Federation of Gynecology and Obstetrics (FIGO) score was 0-4 in 33.3%, 5-6 in 46.7%, and ≥ 7 in 20% of patients. Prior treatment included methotrexate (100%) and actinomycin D (7%). Median follow-up was 25 months, and median number of avelumab cycles was 8 (range, 2-11). Grade 1-2 treatment-related adverse events occurred in 93% of patients, most commonly (≥ 25%) fatigue (33.3%), nausea/vomiting (33.3%), and infusion-related reaction (26.7%). One patient had grade 3 uterine bleeding (treatment unrelated). Eight patients (53.3%) had hCG normalization after a median of 9 avelumab cycles; none subsequently relapsed. Probability of normalization was not associated with disease stage, FIGO score, or baseline hCG. One patient subsequently had a healthy pregnancy. In avelumab-resistant patients (46.7%), hCG was normalized with actinomycin D (42.3%) or combination chemotherapy/surgery (57.1%).

Conclusion: In patients with single-agent chemotherapy-resistant GTT, avelumab had a favorable safety profile and cured approximately 50% of patients. Avelumab could be a new therapeutic option, particularly in patients who would otherwise receive combination chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibiotics, Antineoplastic / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Chorionic Gonadotropin / blood*
  • Dactinomycin / therapeutic use
  • Drug Resistance, Neoplasm
  • Fatigue / chemically induced
  • Female
  • Follow-Up Studies
  • Gestational Trophoblastic Disease / blood
  • Gestational Trophoblastic Disease / drug therapy*
  • Humans
  • Injection Site Reaction / etiology
  • Methotrexate / therapeutic use
  • Middle Aged
  • Nausea / chemically induced
  • Pregnancy
  • Retreatment
  • Vomiting / chemically induced
  • Young Adult

Substances

  • Antibiotics, Antineoplastic
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Immunological
  • Chorionic Gonadotropin
  • Dactinomycin
  • avelumab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT03135769