Apatinib-pegylated liposomal doxorubicin combo ups survival in ovarian cancer

The addition of the oral, small-molecule tyrosine kinase inhibitor apatinib to pegylated liposomal doxorubicin (PLD) led to a significant improvement in progression-free survival (PFS) among women with platinum-resistant or refractory recurrent ovarian cancer* compared with PLD alone, according to the results of the APPROVE trial presented at SGO 2021.

The efficacy of apatinib for stomach and liver cancer has been reported. [J Clin Oncol 2016;34:1448-1454; J Clin Oncol 2020;doi:10.1200/JCO.2020.38.15_suppl.4507] In an exploratory analysis, apatinib plus chemotherapy showed promise for platinum-resistant recurrent ovarian cancer. [Lancet Oncol 2018;19:1239-1246]

“[There is] increasing evidence [suggesting] that the combination of anti-angiogenic therapy and single-agent chemotherapy can improve outcomes in platinum-resistant ovarian cancer,” noted Dr Tiantian Wang from the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, in her presentation.

As such, Wang and colleagues sought to evaluate the efficacy and safety of apatinib in combination with PLD in this patient setting. A total of 152 participants (median age 55 years) were randomized 1:1 to receive IV PLD 40 mg/m² Q4W up to 6 cycles alone or in combination with apatinib 250 mg QD until disease progression, unacceptable toxicity, or withdrawal of consent. [SGO 2021, abstract 11561]

After a median follow-up of 8.1 months, PFS was longer with the apatinib-PLD regimen than with PLD alone (median, 5.8 vs 3.3 months; adjusted** hazard ratio, 0.44, 95 percent confidence interval, 0.28–0.71; p=0.0005).

With regard to tumour response, the apatinib-PLD regimen also fared significantly better than PLD alone, both in terms of objective response rate (43.1 percent vs 10.9 percent) and disease control rate (84.6 percent vs 57.8 percent; p<0.0001 for both).

The fraction of women who had a reduction in baseline target lesion size was also greater in the apatinib-PLD vs the PLD alone arm (87.8 percent vs 39.2 percent).

Subgroup analysis also favoured apatinib-PLD over PLD alone across all subgroups*** (HRs ranging from 0.11 to 0.76).

The rate of grade ≥3 treatment-emergent adverse events (TEAEs) was higher in the apatinib-PLD vs the PLD alone arm. Hypertension (8.11 percent vs 1.39 percent) and decreased white blood cell count (6.76 percent vs 4.17 percent) were among the most common grade ≥3 TEAEs.

Nonetheless, the apatinib-PLD combination regimen was generally well-tolerated, and toxicities were deemed manageable. “[There were] no unexpected safety signals identified beyond the established safety profile of each agent,” noted Wang.

Data on overall survival is immature; further follow-up is thus warranted. A randomized phase III study in this patient setting is being planned, Wang added.