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

Altmetrics Information
.

Other information
AbstractBackground
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.
All Author(s) ListHui 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.
Name of ConferenceESMO 2016 Congress
Start Date of Conference07/10/2016
End Date of Conference11/10/2016
Place of ConferenceDenmark
Country/Region of ConferenceDenmark
Proceedings TitleAnnals of Oncology
Year2016
Month10
Day1
Volume Number27
Issue Numbersuupl 6
PublisherOxford University Press
LanguagesEnglish-United States

Last updated on 2020-01-12 at 00:08