Efficacy, Safety, and Pharmacokinetics of Axitinib in Nasopharyngeal Carcinoma: A Preclinical and Phase II Correlative Study

Abstract

We hypothesized that axitinib is active with an improved safety profile in nasopharyngeal carcinoma (NPC). We evaluated axitinib in preclinical models of NPC and studied its efficacy in a phase II clinical trial in recurrent or metastatic NPC patients who progressed after at least one line of prior platinum-based chemotherapy. We excluded patients with local recurrence or vascular invasion. Axitinib was started at 5 mg twice daily in continuous 4-week cycles. Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria for more than 3 months. We recruited 40 patients, who received a median of 3 lines of prior chemotherapy. Axitinib was administered for a mean of 5.6 cycles, with 16 patients (40%) receiving ≥6 cycles. Of 37 patients evaluable for response, CBR was 78.4% (95% CI, 65.6%-91.2%) at 3 months and 43.2% (30.4%-56.1%) at 6 months. Grade 3/4 toxicities were uncommon, including hypertension (8%), diarrhea (5%), weight loss (5%), and pain (5%). All hemorrhagic events were grade 1 (15%) or grade 2 (3%). Elevated diastolic blood pressure during the first 3 months of axitinib treatment was significantly associated with improved overall survival (HR, 0.29; 95% CI, 0.13-0.64, = 0.0012). Patient-reported fatigue symptom was associated with hypothyroidism ( = 0.039). Axitinib PK parameters (C and AUC) were significantly correlated with tumor response, toxicity, and serum thyroid-stimulating hormone changes. Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients. .

Apatinib, a novel VEGFR-2 tyrosine kinase inhibitor, for relapsed and refractory nasopharyngeal carcinoma: data from an open-label, single-arm, exploratory study

“…Axitinib, another VEGFR inhibitor, has also been reported to help achieve an ORR of 19% among 37 evaluable patients, including 1 who showed PR, 6 who showed unconfirmed PR, and 22 who showed a stable disease. However, the median time to progression was 5.0 months and median OS was 10.4 months, indicating an inferior curative effect compared with that of apatinib [21]. Adoptive T cell therapy has emerged as a strategy to treat human cancers.…”

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

“…239 Axitinib has good control of disease progression and safety in patients with severe pre-treated NPC. 240 Aflibercept plus docetaxel has achieved preliminary efficacy in Chinese patients with NPC, and this treatment deserves further trials. 241 Mk-2206 is an inhibitor of Akt, which has limited activity in the heavily pre-treated group of patients in a multicenter phase II clinical trial.…”

AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma

“…Recent advances in intensity modulated radiation therapy and its combination with chemotherapy have remarkably improved the efficacy of NPC treatments, especially in the early stage [ 3 – 6 ]. However, more than 70% of NPC cases are diagnosed as advanced-stage disease, and local relapse and distant metastasis are two main reasons for NPC death [ 7 – 9 ]. Therefore, the identification of key biomarkers and characterization of its mechanisms involved in NPC recurrence and metastasis would make a significant difference on the development of individualized treatment for NPC patients.…”