<p>Apatinib in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma: A Phase II, Open-Label, Single-Arm, Prospective Study</p>

Abstract

These authors contributed equally to this work Purpose: Treatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor-2 (VEGFR-2) to inhibit tumour angiogenesis. In the present study, we evaluated the efficacy and safety of apatinib for patients with RR DLBCL. Patients and Methods: In this phase II, open-label, single-arm, prospective study, we enrolled patients aged 14-70 years with treatment failure of at least two chemotherapeutic regimens using Simon's two-stage design. All patients were administered apatinib at an initial dose of 500 mg on a 4-week cycle at home and visited the outpatient clinic every two cycles to evaluate efficacy and to record adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), and overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.). Results: From January 2017 to February 2019, we screened 35 patients and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses, and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate of 71.9%. The median PFS and OS were 6.9 (95% confidence interval [CI], 5.8-7.9) and 7.9 months (95% CI, 7.0-8.7), respectively. The median DoR was 5.0 months (95% CI, 3.5-6.5) for patients who achieved PR. The most common grade 3-4 adverse events (AE) were hypertension (12.6%), hand-foot syndrome (9.4%), and leucopenia (6.3%). No apatinib-related deaths were noted. Conclusion: Home administration of apatinib shows promising efficacy and manageable AEs in patients with RR DLBCL.

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

“…In addition, several recent phase II clinical trials have confirmed that apatinib monotherapy has certain efficacy and good safety in the treatment of advanced cholangiocarcinoma (ORR, 11.5%) (65), relapsed or refractory diffuse large B-cell lymphoma (ORR, 43.8%) (66), metastatic or locoregionally recurrent nasopharyngeal carcinoma (ORR, 36.4%) (67), and radioiodine-refractory differentiated thyroid cancer (ORR, 80%) (68). These clinical trials have only initially shown the efficacy and safety of apatinib in these malignancies (Table 6).…”

New agents and regimens for diffuse large B cell lymphoma

“…Apatinib is an orally administered novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2 (VEGFR-2), which involves in lymphomagenesis. Home administration of apatinib with regular outpatient follow-up produced encouraging antitumor effects in r/r DLBCL in an open-label, single-arm, prospective study [ 106 ]. ORR of 43.8% and a disease control rate of 71.9% were reported, with a median DoR of 5.0 (95% CI 3.5–6.5) months ( n = 32).…”

“…ORR of 43.8% and a disease control rate of 71.9% were reported, with a median DoR of 5.0 (95% CI 3.5–6.5) months ( n = 32). The most common toxicities of any grade were hypertension (62.5%), leukopenia (40.6%), and hand-foot syndrome (40.6%) [ 106 ]. The relatively high response rate attained by apatinib deserves future investigation of drug combination strategies.…”

Anti-Tumor Effect of Apatinib and Relevant Mechanisms in Liposarcoma

“…Apatinib is a novel, small molecule anti-angiogenesis agent that inhibits VEGFR-2, c-kit, Src, and Ret. Phase II clinical trials have shown that Apatinib has manageable side effects and promising efficacy against various solid tumors ( 21 – 23 ). Two case studies suggested that Apatinib could benefit patients with liposarcoma ( 11 , 12 ).…”