Results of the phase 2 APPROVE trial demonstrated significant prolongation of progression-free survival with the addition of apatinib to PLD in patients with platinum-resistant or refractory recurrent ovarian cancer, with an adverse event profile consistent with that previously described for apatinib and PLD.
The multicenter, randomized, controlled, open-label, phase 2 APPROVE trial evaluated the efficacy and safety of the VEGFR-2 tyrosine kinase inhibitor, apatinib, in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant or refractory recurrent ovarian cancer. The results of this trial were reported at the 2021 Society of Gynecologic Oncology Annual Meeting.
Between March 22, 2018, and November 16, 2020, the APPROVE trial enrolled patients with histologically confirmed nonmucinous ovarian, primary peritoneal cancer, or fallopian-tube cancer with disease progression during, or within 6 months of discontinuing, any previous line of platinum-based chemotherapy, and with ≥1 measurable and/or nonmeasurable lesions. Eligible patients were randomly assigned (1:1) to receive PLD alone (40 mg/m2 intravenously every 4 weeks, for up to 6 cycles), or in combination with apatinib (250 mg once daily) until disease progression, unacceptable toxicity, or consent withdrawal. Patient stratification was by previous platinum-sensitive relapsed (yes vs no) and platinum-free interval (<3 vs 3-6 months from last platinum therapy to subsequent progression). The primary end point was progression-free survival (PFS) in the intent-to-treat (ITT) population; secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.
A total of 152 patients were enrolled in the study; of these, 78 patients received the apatinib/PLD combination, and 74 patients received PLD alone. In the ITT population, at a median follow-up of 8.1 months, median PFS was significantly longer with apatinib/PLD combination therapy compared with PLD alone (5.8 months vs 3.3 months; hazard ratio, 0.41; P = .0001). In patients with evaluable disease, the ORR (37.7% vs 9.5%; P = .0002) and DCR (82.0% vs 58.7%; P = .0050) were also significantly improved. OS data are immature at this time.
The adverse event profiles were consistent with those previously described for both agents. The most frequent adverse events with apatinib therapy were hypertension and hand-foot syndrome.
Based on these results, the investigators concluded that the addition of apatinib to PLD resulted in significant prolongation of PFS in patients with platinum-resistant or refractory recurrent ovarian cancer, with an adverse event profile consistent with that previously described for apatinib and PLD.
Source: Wang T, Li N, Tang J, et al. Apatinib combined with pegylated liposomal doxorubicin (PLD) versus PLD for platinum-resistant recurrent ovarian cancer (APPROVE): a multicenter, randomized, controlled, open-label, phase II trial. Gynecol Oncol. 2021;162(suppl_1):S42.
