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Apatinib shows promise for ovarian cancer
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Oral apatinib in combination with etoposide appeared effective with manageable toxicities among women with platinum-resistant or -refractory ovarian cancer, according to results from a phase 2 clinical trial.
Further, the combination could be administered at home without an infusion pump and hospital admission.
“To our knowledge, this is the first study to evaluate the combination therapy of a VEGFR tyrosine kinase inhibitor and oral etoposide in patients with ovarian cancer,” Chun-Yan Lan, MD, of the department of gynecologic oncology at State Key Laboratory of Oncology in South China, and colleagues wrote. “The efficacy in this study was promising compared with that in other studies that combine antiangiogenic therapy and chemotherapy.”
Apatinib (YN968D1, LSK BioPharma) — a novel, small-molecule TKI that selectively inhibits VEGFR-2 — is available for treatment in mainland China.
Previous studies have shown apatinib encouraged antitumor activity with tolerable toxicities in several malignant tumors.
A phase 2 study among 29 patients with platinum-resistant ovarian cancer showed apatinib monotherapy led to an objective response rate of 41.4% (95% CI, 23.3–59.4), and a median PFS of 5.1 months (95% CI, 3.8–6.5).
For this single-arm prospective study, researchers assigned 35 women with platinum-resistant or -refractory ovarian cancer an initial 500-mg oral dose of apatinib on a continuous basis, and 50 mg oral etoposide once daily on days 1 to 14 of a 21-day cycle for a maximum of six cycles.
Patients continued treatment — regardless of combination stage or monotherapy — until progression, patient withdrawal or extreme toxicity.
The number of patients who achieved an objective response based on Response Evaluation Criteria in Solid Tumors, version 1.1, served as the primary endpoint.
Median duration of follow-up at the time of data analysis was 4.5 months.
At data cutoff on December 17, 2017, 13 of 35 patients had disease progression or had died, one of whom discontinued treatment before progression.
Eighteen patients did not experience disease progression, 15 of whom remained on treatment.
Nineteen of 35 patients (54%; 95% CI, 36.6-71.2) in the intent-to-treat population and 19 of 31 patients (61%; 95% CI, 42.2-78.2) in the per-protocol population experienced an objective response.
Thirty patients (86%; 95% CI, 69.7-95.2) in the intent-to-treat population experienced disease control, with similar results observed in the per-protocol population.
Of the 19 patients with an objective response, six experienced disease progression or died at data cutoff.
The median duration of response was 7.4 months (95% CI, 2.3-12).
The median PFS was 8.1 months (95% CI, 2.8-13.4)
The most commonly observed grade 3 or grade 4 adverse events included neutropenia (50%), fatigue (32%), anemia (29%) and mucositis (24%).
Two patients experienced serious adverse events — one with anemia and anorexia, and the other with increased ascites related to disease progression.
“The data in our study, together with the results from other trials with an antiangiogenic tyrosine kinase inhibitor combined with chemotherapy, support the investigation of the combination therapy of apatinib with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer in a large phase 3 trial,” researchers wrote.
The treatment of platinum-resistant ovarian cancer has remained a challenge, with a goal of maximizing treatment response while minimizing toxicity and hospital stay, Charlie Gourley, MD, professor of medical oncology at Cancer Research UK Edinburgh Centre at University of Edinburgh, and director of the Nicola Murray Centre for Ovarian Cancer Research, United Kingdom, wrote in a related editorial.
“The emphasis on preventing hospital visits by use of an oral combination is commendable; it will be important for future studies of this combination to include patient-reported outcomes to ensure that this convenience is not at the expense of toxicity,” Gourley wrote. – by Melinda Stevens
Disclosures: The authors reports no relevant financial disclosures. Gourley reports advisory board roles with AstraZeneca, Clovis, Foundation One, Nucana, Roche and Tesaro; lecturer roles with AstraZeneca, Roche and Tesaro; research funding to his institution from Aprea, AstraZeneca, Novartis, Nucana, and Tesaro; and that he is a co-inventor on the following patents: PCT/US2012/040805, and PCT/GB2013/053202, 1409479.1, 1409476.7 and 1409478.3.
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