Preliminary study of PD-1 inhibitor in the treatment of drug-resistant recurrent gestational trophoblastic neoplasia

Abstract

Objective: To investigate the therapeutic effect of programmed cell death receptor 1 (PD-1) inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia (GTN). Methods: Clinicopathological features, previous treatments, PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab， in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed. Results: (1) Clinicopathological features: the average age of onset of 8 GTN patients was 32.9 years old (31-39 years old); pathological types: choriocarcinoma in 7 cases, epithelioid trophoblastic tumor in 1 case. International Federation of Gynecology and Obstetrics (FIGO) stages: stage Ⅲ in 5 cases, stage Ⅳ in 3 cases; FIGO score: 4 patients with 7-12 points (high-risk group) and 4 patients with ≥13 points (ultra high-risk group). All the 8 patients had lung metastasis, 2 patients with brain metastasis, 1 patient with kidney and 1 patient with intestinal metastasis. (2) Previous treatments: ① Chemotherapy: 8 patients with GTN received an average of 21.1 courses (5-30 courses) of chemotherapy; the main route was systemic intravenous chemotherapy. One patient received intrathecal methotrexate chemotherapy due to brain metastasis. ② Surgery: 7 of 8 patients with GTN received surgical treatment, including 5 cases of pelvic surgury, 6 cases of pulmonary lobectomy and 1 case of right hemicolectomy. ③ Radiotherapy: 2 of 8 patients with GTN received radiotherapy, among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis, and the other one received radiotherapy for lung, right sacroiliac joint and skull for a total of 22 times. (3) PD-1 inhibitor treatment: 8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9 (2-12 courses). Six patients appeared Ⅰ-Ⅱ grade of immune related adverse events (AE), and no severe AE occurred. (4) Prognosis: after 2-3 courses of PD-1 inhibitor treatment, serum β-hCG level came to normalization in 4 patients. They were followed up for 2-7 months without any recurrence after 0-9 courses of consolidation treatment. One patient received 12 courses of PD-1 inhibitor treatment. The serum β-hCG level normalized after the 6th courses but increased 1 months later, and then received bevacizumab treatment due to the progression of the disease. The remaining 3 patients received other chemotherapy regiments due to disease progression during PD-1 inhibitor treatment. Conclusions: PD-1 could be used as a remedial treatment for drug-resistant recurrent GTN, with a high effective rate and relatively mild AE. However, more cases need to be accumulated clinically and efficacy should be comprehensively evaluated in combination with pathology and immunohistochemical examination.