Apatinib/Doxorubicin Combination Improves PFS Over Single Agent in Ovarian Cancer

Adding apatinib to pegylated liposomal doxorubicin improved median progression-free survival (mPFS) compared with doxorubicin alone in patients with platinum-resistant or refractory ovarian cancer, according to results of the APPROVE trial (NCT04348032), presented at the Society of Gynecologic Oncology (SGO) Virtual Annual Meeting on Women’s Cancer.¹

The phase 2 randomized trial enrolled 152 patients. Patients were stratified by previous platinum-sensitive relapse and platinum-free interval. Eligibility was based on histologically-confirmed non-mucinous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, disease progression during or within 6 months of discontinuing prior platinum-based chemotherapy, and ECOG performance status of 0 to 1. The primary end point was PFS and secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.

According to Tiantian Wang, MD, who presented on behalf of colleagues, to detect an improvement in PFS, the study was powered at 80% at a 2-sided 5% significance level. Further, “the primary analysis was performed when 86 events had occurred,” Wang, of the National Cancer Center and National Clinical Research Center for Cancer, in Beijing, China, said.

After undergoing a 1:1 randomization, patients received 250 mg of apatinib once daily and 40 mg/m2 of doxorubicin every 4 weeks or doxorubicin monotherapy. Both arms continued until disease progression, unacceptable toxicity, or patient withdrawal of consent. After randomization, the treatment arm had 78 patients and the control arm had 74 patients. Four patients in the treatment arm withdrew from the study and 2 patients withdrew from the study in the control arm.

At data cutoff on January 28, 2021, 12 patients continued treatment, and 62 patients discontinued because of progression (39 patients), withdrawn consent (13), adverse effects (3), death (1), and other reasons (6). In the control arm, 4 patients continued and 68 patients discontinued because of progression (46), withdrawn consent (6), death (1), and other (15).

At baseline, patient characteristics were balanced between the 2 arms of the study. The median age in the treatment arm was 54 years (range, 22-76), median age in the control group was 56 years (range, 33-72), and the majority of patients were ECOG performance status 1 in the treatment group (74.4%) and control group (62.2%). All patients in the treatment group were identified as having serous/adenocarcinoma by histologic confirmation compared with 94.6% in the control group.

In the treatment group, the majority (69.2%) had stage III disease; similarly, the majority of patients in the control group had stage III (74.3%) disease. In the treatment group, the majority (96.2%) had no previous antiangiogenic therapy and in the control group, 100% of patients had no previous antiangiogenic therapy.

The investigators reported 87 events in the PFS intention-to-treat population. The median PFS for the treatment group was 5.8 months and the control group was 3.3 months (HR, 0.44; 95% CI, 0.28-0.71; P = .0005).

“The study met its primary objective demonstrating a significant improvement in PFS with the addition of apatinib,” Wang said.

The ORR in the treatment group (n = 65) was 43.1% (95% CI, 30.8%-56.0%) and in the control group, ORR was 10.9% (95% CI, 4.5%-21.2%). Wang said the tumor response ORR was significant (P < .0001).

In the treatment arm, there was 1 (1.5%) complete response, 27 (41.5%) partial responses, 27 (41.5%) patients had stable disease, and 10 (15.4%) patients had progressive disease. In the control group (n = 64), there were 3 (4.7%) complete responses, 4 (6.3%) partial responses, 30 (46.9%) patients had stable disease, and 27 (42.2%) patients had progressive disease. In the treatment arm, DCR was 84.6% compared with 57.8% in the control arm (P = .0007).

Regarding changes in the target lesions, Wang reported that in the treatment group, 87.8% of patients had a decrease from baseline, whereas, in the control group, 39.2% of patients had a decrease in lesion size.

“Subgroup analysis of PFS favored the combination treatment compared with the single-agent therapy,” Wang said.

The most common all-grade treatment-emergent adverse effects (TEAEs) in the treatment arm were decreased white blood cell count (63.5%), decreased neutrophil count (58.1%), oral ulcer (28.4%), and anemia (25.7%). In the control arm, the most common all grade TEAEs were decreased white blood cell count (55.7%), decreased neutrophil count (41.7%), nausea (27.8%), and anemia (25.0%). In the treatment arm, common TEAEs grade ≥3 were decreased neutrophil count (14.9%), hypertension (8.1%), and decreased white blood cell count (6.8%). In the control group, common TEAEs grade ≥3 were decreased neutrophil count (8.3%) and decreased white blood cell count and anemia, both reported at 4.2%.

Wang said apatinib plus doxorubicin was generally well tolerated with manageable adverse effects and no unexpected safety signals beyond those that were reported for each drug individually were reported. OS data are not currently available, so further follow-up is needed.

_Reference

_{Wang T, Li N, Tang J, et al. Apatinib combined with pegylated liposomal doxorubicin (PLD) versus PLD for platinum resistant recurrent ovarian cancer (APPROVE). Presented at: Society of Gynecologic Oncology 2021 Virtual Annual Meeting on Women's Cancer; March 19-25, 2021; Virtual. Abstract 70.}