730P - A phase II study on combination of axitinib and transarterial chemoembolization (TACE) for treatment of inoperable hepatocellular carcinoma (HCC)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Hepatobiliary Cancers
Presenter Stephen Chan
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors S.L. Chan1, W. Yeo2, F. Mo2, L. Li3, K. Lee4, P. Hui2, B. Ma2, T.S.K. Mok5, A.T.C. Chan5, P.B.S. Lai6, S.C.H. Yu7
  • 1Clinical Oncology, The Chinese University of Hong Kong, 1111 - Shatin/HK
  • 2Clinical Oncology, The Chinese University of Hong Kong, Shatin/HK
  • 3Clinical Oncology, Prince of Wales Hospital, NA - Shatin/HK
  • 4Surgery, Prince of Wales Hospital, Shatin/HK
  • 5Dept. Of Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, Shatin/HK
  • 6Surgery, The Chinese University of Hong Kong, Shatin/HK
  • 7Imaging And Interventional Radiology, The Chinese University of Hong Kong, Shatin/HK

Abstract

Aim

TACE is associated with an upregulation of VEGF leading to revascularization. Axitinib is a potent and selective inhibitor of VEGFR1, 2 and 3. We hypothesized that the addition of axitinib to TACE has synergistic activity by abolishing the VEGF driven signal after TACE. To prove this concept, we designed a phase II study to evaluate the efficacy and safety of the combination for treatment of inoperable HCC.

Methods

This is an investigator-initiated phase II single-arm study. The target sample size is 50. Key eligibility criteria include confirmed diagnosis of inoperable HCC; Child's A liver function; ECOG PS 0-2; absence of prior systemic nor TACE treatment; the absence of main portal vein thrombosis or distant metastases. Treatment consists of 8 weekly cycle of axitinib 5mg twice daily. In each cycle, TACE is administered at 5th week when there is radiologically viable tumour and absence of ≥grade 3 toxicity from axitinib. Axitinib is withheld 24h before each TACE, and resumed 24h after TACE when patients (pts) have preserved liver function. Reassessment imaging is done every 8 weeks. In the 1st year, each pt is treated with a maximum number of 6 cycles of TACE. Pt is put on maintenance axitinib alone if there is no PD after 1 year.

Results

Total 50 pts have been accrued. Baseline characteristics: BCLC stage B 38; C 12. Median age 62.1years. At the time of data cutoff on 17 Apr 2014, the median follow-up was 1.32 years. 27 pts have PD, and the median TTP is 10.4 months (95% CI = 5.43-13.72). The median OS is 15.9 months (95% CI = 12.9-not reached). Amongst 42 evaluable pts, the response rate (mRECIST) is 48.8% (7 CR; 14 PR) and the disease control rate is 88.4% (21 CR/PR and 16 SD). Amongst the responders, 3 pts underwent hepatectomy after shrinkage of tumour, and surgical specimen showed extensive tumour necrosis; 2 pts just had portal vein embolization to induce left lobe hypertrophy, and is currently wait-listed for hepatectomy. Total 5 pts could proceed to the axitinib maintenance phase. Common ≥grade 3 toxicity events from axitinib include hypertension (20%), hand foot skin reaction (10%), fatigue (4%) and hyperbilirubinaemia (4%). The toxicity of TACE is not worsened by axitinib.

Conclusions

Combination of axitinib and TACE is associated with high tumour response rate and efficacy in unresectable HCC. Further evaluation with randomized study is indicated. (NCT01352728)

Disclosure

S.L. Chan: received research funding from Pfizer. All other authors have declared no conflicts of interest.