Apatinib–etoposide shows promise in platinum-resistant ovarian cancer
medwireNews: Oral etoposide plus apatinib is associated with a good objective response rate and manageable toxicity in heavily pretreated Chinese women with platinum-resistant or refractory ovarian cancer, according to results of the phase II AEROC study.
The combination of the VEGFR2 tyrosine kinase inhibitor apatinib and the topoisomerase inhibitor etoposide led to an objective response in 54% of 35 patients enrolled in the trial, report Xin Huang (Sun Yat-sen University Cancer Center, Guangzhou, China) and colleagues in The Lancet Oncology – a figure that Charlie Gourley (University of Edinburgh, UK) describes in an accompanying comment as “an impressive proportion.”
A further 31% of women had stable disease, giving a disease control rate of 86%. And the median progression-free survival was 8.1 months, a duration that “suggests the responses are durable, which is very important in this patient group, for whom treatment options are running out,” notes Gourley.
The participants of this single-arm study received continual apatinib at a dose of 500 mg once daily, while 50 mg etoposide was given once daily on days 1–14 of each 21-day cycle for a maximum of six cycles. The researchers selected this combination of drugs because it has “the advantage of home administration without an infusion pump and hospital admission.”
Although all of the participants experienced at least one adverse event, most were mild or moderate in severity. The most common grade 3 or 4 adverse events were neutropenia, fatigue, anemia and mucositis, which were experienced by 50%, 32%, 29%, and 24% of women, respectively.
The majority of patients required dose reductions of both apatinib (82%) and etoposide (77%), and 12% discontinued the study due to unacceptable toxicity.
Huang et al point out that “[a]dverse events were usually manageable with appropriate intervention, and the treatment was continued in nearly all of the women after dose modifications.” Nonetheless, they suggest that future studies should use a lower starting apatinib dose and give etoposide for only 10 days of every 3 weeks.
Still, the promising efficacy and manageable toxicity of this combination means that “further study in phase 3 trials is warranted,” conclude the researchers.
The commentary author writes: "The emphasis on preventing hospital visits by use of an oral combination is commendable; [but] 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.”
By Catherine Booth
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