Combining the vascular endothelial growth factor (VEGF) receptor–targeting tyrosine kinase inhibitor apatinib with oral etoposide in people with platinum resistant or refractory ovarian cancer has shown promising efficacy and manageable toxicity in a Phase 2 study.
Angiogenesis was a “hallmark” process in cancer, and antiangiogenic therapy, including anti-VEGF antibodies and multireceptor tyrosine kinase inhibitors, has been shown to be an attractive therapeutic strategy for ovarian cancer.
“Increasing evidence suggests that the combination of antiangiogenic therapy and single-agent chemotherapy improves the outcome of platinum-resistant ovarian cancer,” Chun-Yan Lan, MD, of the Collaborative Innovation Center for Cancer Medicine at Sun Yat-sen University Cancer Center in Guangzhou, China, and colleagues wrote in.
The investigators chose apatinib because it has shown encouraging antitumor activities and tolerable toxicities in several malignant tumors and was available in mainland China, they said.
The single-arm prospective study enrolled 35 women aged 18-70 years with heavily pretreated ovarian cancer that was refractory to platinum (defined as progression during the initial platinum-based treatment) or resistant to platinum (defined as progression within 6 months after the last platinum treatment).
Women were treated with apatinib at an initial dose of 500 mg once daily on a continuous basis and with oral etoposide at a dose of 50 mg once daily on days 1-14 of a 21-day cycle. Oral etoposide was administered for a maximum of six cycles. Dose modifications, including dose interruptions, were allowed in order to manage adverse events.
Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint of the study was the proportion of patients achieving an objective response according to Response Evaluation Criteria in Solid Tumors (RECIST). The study authors analyzed efficacy data using three populations: intention-to-treat, per-protocol, and safety populations.
Results showed that 19 of 35 patients achieved an objective response (54%; 95% confidence interval, 36.6%-71.2%) in an intention-to-treat analysis. In the per-protocol population, 19 of 31 patients (61%; 95% CI, 42.2%-78.2%) achieved an objective response.
Median progression-free survival was 8.1 months (interquartile range, 4.3-14.6; 95% CI, 2.8-13.4), and the median duration of response was 7.4 months (IQR, 4.0-13.0; 95% CI, 2.3-12.0).
The most common grade 3 or 4 adverse events reported were neutropenia (n = 17), fatigue (n = 11), anemia n = 10), and mucositis (n = 8). Serious adverse events were reported in two patients who were admitted to the hospital.
Dose reductions were required in 82% (n = 28) of 34 patients on apatinib and 77% (n = 26) for etoposide. The authors said they would suggest future studies use a lower starting dose of apatinib and give etoposide for 10 days rather than 14.
“Our study showed that the combination therapy of apatinib with oral etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant or platinum-refractory recurrent ovarian cancer and further study in phase 3 trials is warranted,” the study authors concluded.
They said that a strength of their study was that both apatinib and oral etoposide were able to be given orally without the need for hospital admission or an infusion pump, factors that could improve adherence and cost effectiveness for patients.
However, they noted that one limitation was that it was a single-arm study with no control group, which meant the selection bias could not be ruled out.
Source: Lan CY et al. Lancet Oncol. 2018 Aug 3..