Source: Sun Yat-sen University Cancer Center
Written by: Sun Yat-sen University Cancer Center
Edited by: Wang Dongmei

Innovation! The latest research on the treatment for patients with ovarian cancer conducted by the team led by Professor Xin Huang and Professor Chunyan Lan from Sun Yat-sen University Cancer Center was published online in Lancet Oncology. This is the first time that the clinical trial directed by gynecologic oncologists from Chinese mainland has been published in Lancet Oncology－the top international medical oncology journal since its publication, which is a historic landmark.

Background

Ovarian cancer is the leading cause of death in patients with gynecologic malignancies. In 2015, there were approximately 52,100 new cases of ovarian cancer and 22,500 deaths related to ovarian cancer in China. Most women present with advanced disease at diagnosis. Approximately 75% of patients with advanced ovarian cancer will eventually relapse. Almost all patients with recurrent disease ultimately develop platinum resistance, which results in death. The 5-year overall survival rate of advanced stage disease is less than 30%. For platinum-resistant ovarian cancer, a non-platinum-based agent (i.e., liposomal doxorubicin, weekly paclitaxel with or without pazopanib, topotecan, gemcitabine, and etoposide) is preferred. However, the response rates to sequential therapy using these single agents remain at 10–30%. There is a need to develop new drugs or treatment regimens to achieve higher responses.

Anti-angiogenic therapy, including anti-vascular endothelial growth factor (VEGF) antibodies and vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs), is shown to be an attractive therapeutic strategy for ovarian cancer. Moreover, increasing evidence has suggested that the combination of anti-angiogenic therapy and single-agent chemotherapy improves the outcome of platinum-resistant ovarian cancer. In the AURELIA study, treatment with the combination of bevacizumab and chemotherapy achieved a better progression-free survival (PFS) in patients with platinum-resistant or platinum-refractory ovarian cancer when compared with chemotherapy alone (median 6.7 months versus 3.4 months). Furthermore, in the MITO 11 trial, patients with platinum-resistant or platinum-refractory ovarian cancer treated with pazopanib plus paclitaxel had a significantly longer PFS than the patients treated with paclitaxel only (median 6.35 months versus 3.49 months). However, most of anti-angiogenic drugs are not available in mainland China. Therefore, the team led by professor Xin Huang and Chunyan Lan focused on the new anti-angiogenic drug apatinib.

Innovative results

Apatinib is one of oral small-molecule TKIs, which selectively binds to and inhibits VEGFR2. Several trials have demonstrated the anti-tumor activities of apatinib in a variety of malignancies. In 2014, apatinib has been approved by the China Food and Drug Administration in patients with advanced gastric cancer. Moreover, oral etoposide which is one of the options for patients with recurrent ovarian cancer, is a topoisomerase II inhibitor, inhibit enzyme-mediated DNA ligation causing the accumulation of double-stranded breaks. Some preclinical data revealed that the combination of apatinib and oral etoposide had synergy and were not necessary to have toxicities overlaps. Therefore, from the beginning of the design of the trial, the team led by Professor Xin Huang and Professor Chunyan Lan as well as Professor Huiqiang Huang from the Department of Medical Oncology sincerely collaborate and innovate determinedly as well as try boldly to adopt the oral administration combined apatinib with etoposide for a simpler treatment.

In August 2016, a clinical study entitled “Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study” was conducted by the team. In total, 35 patients with platinum-resistant or platinum-refractory ovarian cancer were enrolled. Objective responses were achieved in 19 (54.3%) patients of 35 patients, and disease control was obtained in 30 (85.7%) patients. The median PFS was 8.1 months (95% CI: 2.8-13.4). Most of the toxicities were mild and manageable.

Patient benefit

In this study, the team by Professor Xin Huang and Professor Chunyan Lan first proposed the novel combination of apatinib and oral etoposide and encouraging results were observed. In addition, it is noteworthy that, compared with the traditional single chemotherapy, the combination of apatinib and oral etoposide has the advantage of home administration without an infusion pump and hospitalization, thus effectively improving the compliance of patients as well as their quality of life. Besides, the length of hospitalization and treatment cost will be significantly reduced and a large number of medical resources will be saved due to the therapeutic regimen, which is very suitable for patients suffering the refractory and recurrent ovarian cancer as a common treatment, especially for developing countries like China where it has a good prospect for clinical application.

The publication of this clinical trial in the international authoritative journal Lancet Oncology fully reflects the high recognition of this research by international peers. At the same time, it also serves as a pioneer of the all orally administered therapy for platinum-resistant ovarian cancer. Further study in phase 3 trials is warranted.

Link to the paper: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30349-8/fulltext