Axitinib in recurrent or metastatic nasopharyngeal carcinoma (NPC): final result of a phase 2 clinical trial with pharmacokinetic (PK) correlation
Refereed conference paper presented and published in conference proceedings

替代計量分析
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其它資訊
摘要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.
著者Hui EP, Ma BB, Mo F, Kam MK, Chan SL, Loong HH, Ho R, Leung SF, King AD, Wang K, Ahuja A, Chan CM, Hui CW, Wong CH, Chan ATC.
會議名稱ESMO 2016 Congress
會議開始日07.10.2016
會議完結日11.10.2016
會議地點Denmark
會議國家/地區丹麥
會議論文集題名Annals of Oncology
出版年份2016
月份10
日期1
卷號27
期次suupl 6
出版社Oxford University Press
語言美式英語

上次更新時間 2020-20-11 於 00:38