Camrelizumab plus apatinib demonstrated efficacious anti-tumor activity and could be a worthwhile salvage therapy in high-risk chemorefractory or relapsed gestational trophoblastic neoplasia.
Treatment with camrelizumab (SHR-1210) plus apatinib (Aitan) may prove to be a viable salvage therapy option for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia in light of its promising antitumor activity and tolerable safety profile, according to results from the phase 2 CAP 01 study (NCT04047017) published in The Lancet Oncology.
After a median follow-up of 18.5 months, investigators reported an objective response rate of 55% (95% CI, 32%-77%) among those who received the combination. Additionally, 50% of responders had a complete response (CR; 95% CI, 27%-73%).
“Camrelizumab combined with apatinib showed promising activity and acceptable toxicity in
patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. In addition to determining the contribution of apatinib for these patients in the clinical setting, the use of immune checkpoint inhibitors combined with chemotherapy for heavily-treated patients and up-front use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia warrant investigation,” investigators wrote.
A total of 20 patients enrolled on the study and received the drug combination, 95% of whom had been diagnosed with choriocarcinoma and 1 patient had a placental site trophoblastic tumor. The median time from antecedent pregnancy to enrolment was 3.1 years. The most common prior treatment were a combination of etoposide, methotrexate, and dactinomycin plus cyclophosphamide and vincristine (n = 19) and floxuridine, dactinomycin, etoposide, and vincristine (FAEV) in (n = 16).
The patient who had a placental site trophoblastic tumor had a Federation of Gynecology and Obstetrics score of 12 at diagnosis and 16 at enrollment; they also had stage IV disease and liver metastases. Patients underwent full term caesarean section during antecedent pregnancy. The interval from antecedent pregnancy to enrollment was 5.2 years.
Patients were given 200 mg of camrelizumab intravenously every 2 weeks, and apatinib at 250 mg orally once per day. The trial enrolled patients between the ages of 18 to 70 years old who had chemorefractory or relapsed gestational trophoblastic neoplasia. Patients were required to have received 2 or more previous lines of therapy.
In total, 53% (95% CI, 29%-76%)of patients with choriocarcinoma had an objective response during the post-hoc analysis. The median number of treatment cycles until an objective response was reached was 3.0. For the patient with the placental site trophoblastic tumor a partial response was achieved following 3 cycles of treatment; treatment was then discontinued due to treatment-related adverse effects (TRAEs). The patient was switched to a FAEV regimen, but died 8 months thereafter.
The median duration of response was not reached, and 45% of patients discontinued the treatment following disease progression and switched to a salvage therapy. Of these patients, 7 had a relapse by the cutoff date and 5 had a CR to the chemotherapy regimens that had been unsuccessful prior to enrollment.
One patient died from chemorefractory disease, and another progressed following salvage therapy, although they were still seeking an effective salvage chemotherapy regimen as of May 2021.
After enrollment, 11 patients had surgery after enrolling, with 5 receiving pulmonary metastasectomies, 3 had hysterectomies, 2 had oophorectomies, and 1 had a liver metastasectomy. Of the 10 patients who had a CR, 5 received surgery.
During the study, 9 progression events were reported. The median progression-free survival was 9.5 months. By the cutoff date, 2 patients had died, and the overall survival (OS) was not reached. In the post-hoc analysis, the 6-month OS was 100% (95% CI, 100%-100%), and the 12-month OS was 90% (95% CI, 66%-97%).
TRAEs of any grade occurred in 90% of patients, and grade 3 TRAEs occurred in 60% of patients. The most common grade 3 TRAEs were hypertension (25%), rash (20%), neutropenia (10%), leukocytopenia (10%), and aspartate aminotransferase increase (10%). Dose reductions occurred in 5 patients because of grade 3 hypertension, and 4 patients delayed treatment because of rash and fever. No grade 4 TRAEs occurred. Grade 3 immune-related AEs occurred in 5 patients, 3 of whom developed a rash and 2 developed neutropenia, all of which were reversible.
Cheng H, Zong L, Kong Y, et al. Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial. Lancet Oncol. Published Online October 5, 2021. doi:10.1016/S1470-2045(21)00460-5