Background Anti-angiogenic therapy combined with chemotherapy could improve the outcomes of patients with
platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits VEGF
receptor 2. We assessed the efficacy and safety of the combination therapy of apatinib and oral etoposide, considering
the potential advantage of home administration without hospital admission, in patients with platinum-resistant or
platinum-refractory ovarian cancer.
Methods In this phase 2, single-arm, prospective study, we recruited patients aged 18–70 years with platinum-resistant
or platinum-refractory ovarian cancer at the Sun Yat-sen University Cancer Center (China). The treatment consisted
of apatinib at an initial dose of 500 mg once daily on a continuous basis, and 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. Treatment was
continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was the
proportion of patients achieving an objective response according to Response Evaluation Criteria in Solid Tumors,
version 1.1. We used Simon’s two-stage design, and analysed efficacy in the intention-to-treat and per-protocol
populations. Safety analyses included enrolled patients who had received at least one dose of study medication, but
excluded those without any safety data. This study is registered with ClinicalTrials.gov, number NCT02867956.
Findings Between Aug 10, 2016, and Nov 9, 2017, we screened 38 and enrolled 35 patients. At the data cutoff date
(Dec 31, 2017), 20 (57%) patients had discontinued the study, and 15 (43%) patients remained on treatment. Objective
responses were achieved in 19 (54%; 95% CI 36·6–71·2) of 35 patients in the intention-to-treat population and in
19 (61%; 42·2–78·2) of 31 patients in the per-protocol population. The most common grade 3 or 4 adverse events were
neutropenia (17 [50%]), fatigue (11 [32%]), anaemia (ten [29%]), and mucositis (eight [24%]). Serious adverse events
were reported in two patients who were admitted to hospital (one patient had anaemia and anorexia; the other patient
had increased ascites due to disease progression). No treatment-related deaths were recorded.
Interpretation The combination of apatinib with oral etoposide shows promising efficacy and manageable toxicities in
patients with platinum-resistant or platinum-refractory ovarian cancer, and further study in phase 3 trials is warranted