Author : adminDate : 2020-03-19 10:12 Attached File :Apatinib-comb-with-oral-etoposide,-platinum-resistant-ovarian-cancer,-AEROC-Phase-2-2018.pdf

Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phas


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