In a Chinese single-institution phase II trial (CAP 01) reported in The Lancet Oncology, Cheng et al found that the PD-1 inhibitor camrelizumab in combination with the antiangiogenic agent apatinib produced a high rate of complete responses in women with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia.

Study Details

The study enrolled 20 patients between August 2019 and March 2020 at Peking Union Medical College Hospital, Beijing. They received 4-week cycles of camrelizumab at 200 mg every 2 weeks plus oral apatinib at 250 mg once daily until disease progression or unacceptable toxicity. Patients had to have received at least two lines of unsuccessful multidrug chemotherapy.

The primary endpoint was objective response rate assessed according to serum human chorionic gonadotropin concentration.

Responses

At data cutoff (May 2021), median follow-up was 18.5 months (interquartile range = 14.6–20.9 months). Objective response was observed in 11 patients (55%, 95% confidence interval [CI] = 32%–77%), with complete response in 10 (53%, 95% CI = 29%–76%). None of the patients with complete response had relapse after discontinuation of camrelizumab and apatinib. Median duration of response was not reached (95% CI = not reached–not reached).

Among the nine patients discontinuing study treatment after disease progression, salvage multidrug chemotherapy regimens produced complete response in seven, including five with complete response to the unsuccessful chemotherapy regimens received prior to study treatment.

Median progression-free survival was 9.5 months (95% CI = not reached–not reached). Death occurred in two patients; overall survival rates were 100% at 6 months and 90% at 12 months.  

Adverse Events

No treatment-related grade 4 or 5 adverse events were observed. The most common grade 3 treatment-related adverse events were hypertension (25%), rash (20%), neutropenia (10%), leukocytopenia (10%), and increased aspartate aminotransferase (AST; 10%). Treatment-related serious adverse events occurred in one patient (5%; elevated AST). Immune-mediated adverse events of any grade occurred in 50% of patients, including rash and reactive cutaneous capillary endothelial proliferation in five patients (25%) each.

The investigators concluded, “Camrelizumab plus apatinib showed promising antitumor activity and acceptable toxicity and could be a salvage therapy option for the treatment of high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combined with chemotherapy for heavily treated patients and upfront use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia are under investigation in phase II trials.”

Yang Xiang, MD, of the National Clinical Research Centre for Obstetric and Gynecologic Diseases, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Natural Science Foundation of China and Jiangsu Hengrui Pharmaceuticals. For full disclosures of the study authors, visit thelancet.com.