Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial
Mené en Chine sur 20 patientes atteintes d'une tumeur gestationnelle trophoblastique récidivante ou réfractaire, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant camrélizumab et apatinib (durée médiane de suivi : 18,5 mois)
Background : Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapyand antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGFreceptor inhibitor) in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Methods : This was a single-arm, open-label, phase 2 trial, done at a single tertiary health-carecentre in Beijing, China. Women (18–70 years) with high-risk (International Federationof Gynecology and Obstetrics score ≥7) chemorefractory or relapsed gestational trophoblasticneoplasia who had received at least two lines of previously unsuccessful multidrugchemotherapy regimens and had an Eastern Cooperative Oncology Group performance status of 0–2 were eligible for inclusion. Patients received 4-week cycles of intravenouscamrelizumab 200 mg every 2 weeks plus oral apatinib 250 mg once per day until diseaseprogression or unacceptable toxicity. The primary endpoint was objective response rate assessed according to serum human chorionic gonadotrophin concentration. Activityand safety were analysed in all patients who received at least one dose of study drug.The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT04047017. Findings : Between Aug 7, 2019, and March 18, 2020, 20 patients enrolled; 19 (95%) were diagnosed with choriocarcinoma and one (5%) had placental site trophoblastic tumour. The median follow-up duration was 18·5 months (IQR 14·6–20·9). The objective response rate was55% (95% CI 32–77); ten (50%; 95% CI 27–73) patients had complete response. The mostcommon grade 3 treatment-related adverse events were hypertension (five [25%] patients),rash (four [20%] patients), neutropenia (two [10%]), leukocytopenia (two [10%]), andaspartate aminotransferase increase (two [10%]). One patient had a treatment-relatedserious adverse event (aspartate aminotransferase 19-times higher than the upper limitof normal). No grade 4 or 5 treatment-related adverse events were reported. Interpretation : Camrelizumab plus apatinib showed promising antitumour activity and acceptable toxicityand could be a salvage therapy option for the treatment of high-risk chemorefractoryor relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combinedwith chemotherapy for heavily-treated patients and upfront use of camrelizumab plusapatinib for patients with high-risk gestational trophoblastic neoplasia are underinvestigation in phase 2 trials.
The Lancet Oncology , 2021