Low-dose apatinib combined with neoadjuvant chemotherapy in the treatment of early-stage triple-negative breast cancer (LANCET): a single-center, single-arm, phase II trial

Abstract

Background: Antiangiogenic therapy combined with chemotherapy could improve pathological complete response (pCR) for breast cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2. We assessed the efficacy and safety of apatinib combined with standard neoadjuvant chemotherapy in patients with triple-negative breast cancer (TNBC). Materials and methods: This single-arm, phase II study enrolled patients aged 18–70 years with previously untreated stage IIA-IIIB TNBC. Patients received oral apatinib at a dose of 250 mg once daily and intravenously docetaxel every 3 weeks for four cycles, followed by epirubicin plus cyclophosphamide every 3 weeks for four cycles. The primary endpoint was the pCR rate in the breast and lymph nodes. Secondary endpoints included objective response rate, event-free survival (EFS), overall survival (OS), and safety. Results: In all, 31 patients were enrolled, and the median follow-up time was 22.9 months (range: 10.1–41.6 months). The pCRs in both breast and lymph nodes were achieved in 17 [54.8%; 95% confidence interval (CI): 36.0–72.7] of 31 patients. Objective responses were achieved in 29 patients (93.5%; 95% CI: 78.6–99.2), and disease control was achieved in 31 patients (100%; 95% CI: 88.8–100.0). The 2-year EFS and 2-year OS were 90.9% and 94.4%, respectively. The five most common treatment-related adverse events were fatigue (51%), hypertension (41%), anorexia (39%), hand–foot syndrome (35%), and diarrhea (32%). Few grade 3 or more adverse events were observed. Conclusion: The combination of apatinib with docetaxel followed by epirubicin plus cyclophosphamide showed excellent efficacy and manageable toxicities; and further randomized controlled phase III trials are warranted. Trial registration: This trial was registered with ClinicalTrials.gov (NCT03243838) on 5 August 2017.

Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer

“…Apatinib, a highly selective VEGFR inhibitor, has exhibited promising efficacy in a Phase II clinical trial for patients with TNBC combined with chemotherapy. The results highlighted not only its effectiveness but also a manageable safety profile ( 104 ). Furthermore, combining Apatinib with a programmed death-ligand 1 (PD-L1) inhibitor in another Phase II trial resulted in favorable outcomes with a controllable safety profile ( 105 ).…”

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

“…[38][39][40] Similarly, trials of conventional chemotherapy combined with antiangiogenic treatments (eg, combination of etoposide with apatinib and docetaxel, epirubicin and cyclophosphamide with Apatinib in a recent 2022 publication) have also shown renewed treatment efficacy without significant unexpected hypertensive toxicity, with data predominantly showing higher rates of lower-grade 1 and 2 hypertension. [41][42][43][44] Interestingly, there is mounting evidence that VEGFiinduced hypertension, which is an on-target treatment response, may predict favorable cancer outcomes in patients and possibly represent a prognostic biomarker. 8,29,36,[45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] In SELECT (A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib in 131I-Refractory Differentiated Thyroid Cancer) trial of patients with advanced thyroid cancer, there was a significant association between lenvatinib-induced hypertension and overall survival.…”

“…38–40 Similarly, trials of conventional chemotherapy combined with antiangiogenic treatments (eg, combination of etoposide with apatinib and docetaxel, epirubicin and cyclophosphamide with Apatinib in a recent 2022 publication) have also shown renewed treatment efficacy without significant unexpected hypertensive toxicity, with data predominantly showing higher rates of lower-grade 1 and 2 hypertension. 41–44…”

Efficacy and safety of apatinib combined with liposomal doxorubicin or paclitaxel versus liposomal doxorubicin or paclitaxel monotherapy in patients with recurrent platinum‐resistant ovarian cancer

“…Apatinib is a novel vascular endothelial growth factor receptor 2 inhibitor, which inhibits endothelial cell proliferation and angiogenesis 9–11 . Notably, several studies have disclosed the effect of apatinib plus chemotherapy in patients with various cancers 12–16 . In terms of patients with recurrent PROC, a study states that apatinib plus etoposide achieves an objective response rate (ORR) of 36.4% and a disease control rate (DCR) of 78.8%; meanwhile, the median progression‐free survival (PFS) is 5.6 months and the median OS is 10.3 months; nevertheless, the sample size is small ( N = 33) and this is a single‐arm study 17 .…”

“…[9][10][11] Notably, several studies have disclosed the effect of apatinib plus chemotherapy in patients with various cancers. [12][13][14][15][16] In terms of patients with recurrent PROC, a study states that apatinib plus etoposide achieves an objective response rate (ORR) of 36.4% and a disease control rate (DCR) of 78.8%; meanwhile, the median progression-free survival (PFS) is 5.6 months and the median OS is 10.3 months; nevertheless, the sample size is small (N = 33) and this is a singlearm study. 17 A further randomized controlled trial reports that the median PFS (5.8 months vs. 3.3 months) and ORR (43.1% vs. 10.9%) are increased in patients receiving apatinib plus pegylated liposomal doxorubicin in contrast with those receiving pegylated liposomal doxorubicin in patients with recurrent PROC.…”