Axitinib in recurrent or metastatic nasopharyngeal carcinoma (NPC): final result of a phase 2 clinical trial with pharmacokinetic (PK) correlation

Background

Axitinib is approved in advanced renal cell cancer patients (pts) who failed one prior systemic therapy. It has also demonstrated potent activity in preclinical models of NPC [Cancer Res 2012; 72 (8 Suppl): A1373].

Methods

We conducted a phase 2 clinical trial of axitinib monotherapy in recurrent or metastatic NPC pts who progressed after ≥1 line of platinum-based chemotherapy (CT). Pts with local recurrence or vascular invasion were excluded. Axitinib was started at 5 mg twice daily in continuous 4-weeks cycles until progression or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR), defined as % of pts achieving complete response (CR), partial response (PR) or stable disease (SD) by RECIST for >12 weeks. Secondary endpoints included time to progression (TTP), overall survival (OS), safety and PK profile. Simon's Minimax 2-stage phase 2 design (P0 = 0.50, P1 = 0.70, type I error 0.05, power 80%) was used to calculate sample size (n = 37; evaluable for response).

Results

We recruited 40 pts. Median age 52 (22-74). M:F = 35:5. Pts received a median of 3 lines of prior CT (range 1-6). As of 31 Mar 2016, the median follow up was 36.1 months. Pts received axitinib for a median of 4.5 cycles (range 1-21), with 16 pts (40%) received ≥ 6 cycles, 7 (18%) pts ≥ 10 cycles and 2 pts ≥ 18 cycles. 9 (23%) pts had dose escalation and 12 (30%) had dose reduction. Of 37 pts evaluable for response, 3-month CBR = 78.4% (95% CI: 65.6-91.2%; 1 confirmed PR, 6 unconfirmed PR, 22 SD). 6-month CBR = 43.2% (30.4-56.1%). Median TTP = 5.0 months (95% CI: 3.9-5.7). Median OS = 10.4 months (6.5-18.6). 1-year survival rate = 45.4%. Treatment-related adverse events by CTCAE, all grades (Gr) in ≥ 25% of pts included: hand-foot 50% (Gr 3: 3%), hypothyroidism 48% (Gr 3: 3%), fatigue 40% (Gr 3: 3%), hypertension 38% (Gr 3: 8%), diarrhea 30% (Gr 3: 5%), pain 28% (Gr 3: 5%), mucositis 28% (Gr 3: 0%). All hemorrhages were Gr 1 (15%) or Gr 2 (3%). Diastolic blood pressure ≥ 90 mmHg was significantly associated with better OS (HR 0.3, p = 0.0016). Axitinib PK parameters and correlations with dose, efficacy and toxicity will be presented.

Conclusions

Single agent axitinib achieved meaningful disease control with manageable toxicity in heavily pretreated NPC.

Clinical trial identification

CCTU-NPC022; ClinicalTrials.gov NCT01249547

Legal entity responsible for the study

Comprehensive Cancer Trials Unit, Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong

Funding

Department of Clinical Oncology, The Chinese University of Hong Kong

Disclosure

All authors have declared no conflicts of interest.