A Phase II, Single-Arm Study of Apatinib and Oral Etoposide in Heavily Pre-Treated Metastatic Breast Cancer

Abstract

IntroductionWe performed this clinical trial to evaluate the efficacy and safety of apatinib and oral etoposide in patients with HER2-negative locally advanced or metastatic breast cancer (MBC).MethodsPatients with HER2-negative MBC previously treated with anthracycline and taxanes and failed ≥1 prior chemotherapy regimens were recruited. The starting dose of apatinib was 500 and 425 mg in patients with ECOG scores of 0–1 and 2, respectively. The etoposide capsules were given at 50 mg/m2 on days 1 to 10 for 21 days. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.ResultsThirty-one eligible patients were enrolled. The median follow-up time was 11 months. The median PFS for all patients was 6.9 months [95% confidence interval (CI) 6.0–7.9], and 6.9 months (95% CI 5.3–8.6) and 6.6 months (95% CI 1.4–11.7) for patients with apatinib 425 and 500mg once daily, respectively. The ORR was 35.5% (11/31). The DCR was 87.1% (27/31). The median OS was 20.4 months (95% CI 11.4–29.3). The median PFS of patients who had hypertension and proteinuria was longer than that for those without hypertension and proteinuria. The most common grade 3/4 treatment-related AEs were hypertension (12/31, 38.7%), fatigue (3/31, 9.7%), thrombocytopenia (3/31, 9.7%).ConclusionApatinib combined with etoposide capsules is effective and tolerable in heavily pretreated, metastatic HER2-negative breast cancer patients. A lower apatinib dose provide equivalent efficacy and reduced toxicity.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT03535961.

Efficacy and Response Biomarkers of Apatinib in the Treatment of Malignancies in China: A Review

“…Hopes are pinned on the combination of apatinib and other drugs. In 2020, a phase II trial showed that apatinib combined with etoposide capsules is effective and tolerable in heavily pretreated, metastatic HER2-negative breast cancer patients (53). Another phase II trial showed that the ORR of an apatinib plus PD-1 inhibitor regimen was markedly higher than the previously reported ORR of anti-PD-1/PD-L1 antibody or apatinib monotherapy in advanced TNBC (54).…”

Targeting CD82/KAI1 for Precision Therapeutics in Surmounting Metastatic Potential in Breast Cancer

“…Oral etoposide was assessed as a valuable and safe option for pre-treated MBC patients [89,90]. Moreover, etoposide with apatinib has been reported to be effective and tolerable in heavily pretreated, metastatic HER2 − negative breast cancer patients [91]. On the other hand, etoposide in combination with irinotecan in a Phase II trial for refractory MBC, was terminated as the interim analysis revealed severe toxicity effects [92].…”

A Real-World Multicentre Retrospective Study of Low-Dose Apatinib for Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer

“…Among 38 patients with advanced non-TNBC [ 6 ], apatinib acquired a median PFS and OS of 4.0 months and 10.3 months, respectively. In addition, the retrospective analysis results revealed that metastatic breast cancer patients had comparable results compared with other trials [ 15 , 16 , 17 , 18 , 20 , 21 , 32 , 33 ] after treatment with apatinib. The median PFS and the OS were 4.7 and 15.4 months, respectively, and the longer period than patients in prior chemotherapy alone studies [ 3 , 31 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ] suggested that apatinib may be used to treat individuals who have developed multidrug resistance to traditional chemotherapy medicines, while the ORR and the DCR were 22.7%, and 80.5%, respectively.…”

“…In recent years, apatinib was used for treating breast cancer and showed a good clinical benefit in both triple negative and non-triple-negative metastatic breast cancer [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. However, whether in clinical trials and real-world studies, high doses of 500 mg or 425 mg are often chosen for treatment, resulting in an inability to tolerate grade III hypertension and proteinuria.…”

“…However, whether in clinical trials and real-world studies, high doses of 500 mg or 425 mg are often chosen for treatment, resulting in an inability to tolerate grade III hypertension and proteinuria. This has often forced patients to stop tyrosine kinase inhibitor (TKI) treatment, which has been a problem for clinicians and patients [ 16 , 17 , 20 , 21 ]. At the same time, recent studies have shown that apatinib therapy with a low dose could improve the efficacy of anti-tumor therapy by normalizing blood vessel with tolerable adverse events.…”