Advanced recurrent platinum-resistant or refractory OC has always been a difficult problem for gynecological tumor treatment. Currently, the treatment methods are limited, and most patients undergo too many lines or multiple courses of chemotherapy, often with a poor physical condition. Initially, two prospective studies demonstrated that apatinib orally administered 500mg per day in patients with platinum-resistant or platinum-refractory OC showed good results. Miao et al. reported the ORR reached 41.4%, DCR reached 68.9% and mPFS reached 5.1 months. But at the same time, the side effects of high doses of Apatinib can seriously affect patient compliance and quality of life [7]. In another phase II study of 500 mg apatinib for EOC, 39.3% of the patients had to interrupt the dose within 1 month, and 32.1% of the patients had to reduce the dose due to severe hand-foot syndrome and hypertension [6]. In our previous published retrospective study, apatinib was the first to show a 61.5% DCR and 4.0 months median PFS in patients with platinum-resistant or platinum-refractory OC treated with 250mg apatinib daily. Because the toxicity was largely tolerable and controllable, the older age group showed higher DCR and longer PFS [10].
Another retrospective study on platinum-resistant or refractory OC showed in patients with biochemical-only relapse, the mPFS was 6 months, with ORR of 26.32% and DCR of 89.47%. And in patients with clinical relapse, the ORR was 36.36% and DCR was 68.18% [17]. This suggests a higher DCR when patients are treated with apatinib for biochemical relapse. Besides, a study combining etoposide with 500mg apatinib showed 54% ORR, 86% DCR and 8.1 months mPFS [6]. This suggests that apatinib combined with etoposide can produce higher DCR and mPFS.
For patients with platinum-resistant or refractory OC, appropriate prolongation of the platinum-free interval will lead to re-sensitization to platinum drugs, which is critical for later platinum reapplication. As a result, a series of platinum-free chemotherapy schemes have emerged and shown certain results. In this study, 250mg apatinib or 250mg apatinib combined with etoposide was given to patients with platinum-resistant or platinum-refractory OC with biochemical recurrence, and ORR, DCR, mPFS, and mOS were analyzed.
Compared with the “intention-to-treat” group in our previous published study, this apatinib monotherapy group had better ORR (32.25% vs 27.7%), and longer mPFS (5.3m vs 4.0m), and higher DCR (77.41% vs 49.2%) [10]. This may be because we started treatment at the time of biochemical relapse in patients in this study, which could inhibit the recurrence of micrometastases earlier. There were no significant differences in patient characteristics and AEs between the two groups.
In this study, when etoposide combination therapy was also given, better ORR (50% vs 32.25%), higher DCR (90% vs 77.41%), longer mPFS (5.3m vs 6.33m), and mOS (24m vs 27m) were obtained compared with the apatinib monotherapy group. There was also no significant difference in AEs between the two groups.
This study has many shortcomings. Firstly, it is a single-center retrospective study with inherent shortcomings and bias. Secondly, the number of patients in the study was small and there were individual differences. Finally, drop-out and loss of follow-up are also causes of efficacy and safety bias.