Introduction/Background*In patients with gestational trophoblastic tumors (GTT) with a FIGO score ≥ 7, or GTT resistant to both standard monotherapies, the recommended polychemotherapy regimen is EMA-CO. In case of resistance to polychemotherapy, the prognosis is poor. The anti-PD-L1 monoclonal antibody avelumab may be effective for GTT resistant to monochemotherapy (You et al JCO 2020). The efficacy data of avelumab in patients with GTT resistant to polychemotherapy enrolled in cohort B of TROPHIMMUN trial (NCT03135769) are presented.

Methodology In cohort B, patients with GTT resistant to polychemotherapy received avelumab 10 mg/kg Q2W until hCG normalization, and for 3 additional cycles thereafter. The primary endpoint was the rate of patients with hCG normalization, following a 2-step Simon design. The cohort was closed prematurely for futility.

Result(s)*2017-2020 : seven patients were treated with the French Gestational Trophoblastic Center (median age was 37 ; choriocarcinoma: 4; placental-site: 1; epithelioid: 1; other: 1) ; stage I/III: 43%/57%; FIGO score 8-10: 43%; score 11-15: 57%. Patients had experienced previous failures to monochemotherapy (n=5), pelvis surgery (n=2), and polychemotherapy (EMA-CO, n=5; EMA-EP, n=1; TP/TE, n=1; APE; n=1). They received a median of 6 avelumab cycles (range: 3-13). Six (85.7%) patients achieved initial hCG stabilization/decline, and one patient (14.2%) had successful hCG normalization after 13 cycles. Another patient experienced favorable hCG decline, but avelumab was discontinued for hemostatic hysterectomy, followed by sustained hCG normalization. The 5 other patients (71.4%) experienced hCG re-increase suggesting avelumab resistance, including two patients who developed brain hemorrhage after 4 cycles (brain metastases in one patient; arteriovenous malformation in one patient who died). The 4 remaining patients were subsequently treated with hysterectomy, other polychemotherapy, including high-dose/bone-marrow-transplant for two; pembrolizumab for one (who died).

Conclusion*TROPHIMMUN is the first trial of immunotherapy in GTT. Contrarily to avelumab suggested effectiveness in patients with monotherapy resistance (Cohort A), avelumab activity was limited in patients with polychemotherapy resistance. Despite initial changes in hCG kinetics in most patients, eventual hCG normalization was rare (14%). The prognosis of patients experiencing polychemotherapy resistance remains poor. Combination treatments with immunotherapy should be considered.