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

Autor: Sylvie Bin, Touria Hajri, Laurence Gladieff, Gilles Freyer, Jérôme Massardier, Daniele Grazziotin, Benoit You, Catherine Mercier, Pascal Rousset, Adeline Roux, Laurent Villeneuve, Pierre-Adrien Bolze, Delphine Maucort-Boulch, Marine Alves-Ferreira, François Golfier, Jean-Pierre Lotz, Florence Joly
Rok vydání: 2020
Předmět:
Zdroj: Journal of Clinical Oncology. 38:LBA6008-LBA6008
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2020.38.18_suppl.lba6008
Popis: LBA6008 Background: Patients with gestational trophoblastic tumors (GTT) resistant to monochemotherapy are treated with historic chemotherapy regimens known to be effective, but toxic. PD-L1 is constitutively expressed in all GTT subtypes (Bolze et al. Int J Gynecol Cancer 2017). HLA-G and natural killer (NK) cells are involved in GTT immune-surveillance. The anti-PD-L1 monoclonal antibody avelumab (Pfizer & Merck KGaA) triggers cytotoxicity through NK cells. The objective of TROPHIMMUN trial was to assess the efficacy of avelumab in patients with chemoresistant GTT. Methods: In the cohort A of this academic multicenter trial (NCT03135769), avelumab was given at 10 mg/kg Q2W in patients with GTT resistant to monochemotherapy. Avelumab was prescribed until hCG normalization, and then for 3 consolidation cycles. The primary objective was the rate of patients with hCG normalization, with a 2 step Simon design. Results: 15 patients (median 34 y old) followed by the French Gestational Trophoblastic Center were treated from Dec 2016 to Sept 2019 (stage I/III: 53%/47%; FIGO score 0-4: 33%; score 5-6: 47%; score >6: 20%). They all had progressed with previous methotrexate, and 1 patient with actinomycin-D. They received median 8 avelumab cycles (range: 2-11). The tolerability was favorable. 93 % of patients developed drug-related grade 1-2 toxicities (86% grade 1), mainly including fatigue (33% patients); nausea-vomiting (33%); infusion-related reactions (27%); thyroid disorder (20%); dry eyes (20%) & diarrhea (20%). A grade 3 uterus bleeding (treatment unrelated) was observed in 1 patient. Median follow-up was 30 months. Successful hCG normalizations were obtained in 8 patients (53%, median 9 avelumab cycles), either during avelumab treatment in 7 patients, or after avelumab discontinuation in 1 patient. None presented relapse afterwards, and 1 patient had a subsequent healthy pregnancy. Avelumab resistances requiring switch to chemotherapy were observed in 7 patients (47%), who normalized hCG with subsequent actinomycin-D (42%), or surgery/polychemotherapy (57%). The likelihood of success with avelumab was not related to the FIGO score, or disease stages. Conclusions: TROPHIMMUN is the first trial of immunotherapy in GTT patients. The anti-PD-L1 monoclonal antibody avelumab was effective, with a favorable safety profile compared to chemotherapy, in patients with resistance to mono-chemotherapy. About 50 % patients could be cured of their chemoresistant diseases. Avelumab may be a new therapeutic option. Clinical trial information: NCT03135769 .
Databáze: OpenAIRE
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