223P - Circulating tumor cell (CTC) count and expression of pERK and pAKT in CTCs as biomarkers for sorafenib efficacy in advanced hepatocellular carcinoma

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Hepatobiliary Cancers
Translational Research
Presenter Jun Li
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors J. Li1, L. Shi2, Y. Yang3, M. Wu2, Z. Yin1
  • 1Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 200438 - Shanghai/CN
  • 2Department Of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 200438 - Shanghai/CN
  • 3Department Of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 200438 - Shanghai/CN

Abstract

Aim

Sorafenib, an orally-active multikinase inhibitor targeting Ras/Raf/ERK pathway, is the first and only drug currently approved to treat advanced hepatocellular carcinoma (HCC). Activation of PI3K/Akt signaling pathway has been demonstrated to mediate acquired resistance to sorafenib in HCC. The purpose of this study was to establish whether CTC count and expression of pERK and pAKT in CTCs predicted outcome in patients with HCC receiving sorafenib.

Methods

Fifty-nine CTC-positive HCC patients treated with sorafenib monotherapy were enrolled. CTC count and expression of pERK and pAKT in CTCs were measured using multicolor immunofluorescence staining following enrichment.

Results

CR, PR, SD, and PD rates were 1.7% (1/59), 18.6% (11/59), 20.3% (12/59), and 59.3% (35/59), respectively. Out of 15 patients whose CTCs contained the pAKT(-)/pERK(+) subtype, CR, PR, SD, and PD rates were 6.7% (1/15), 46.7% (7/15), 20% (3/15) and 26.7 %(4/15), respectively. Disease control rates had a statistically significant difference between pAKT(-)/pERK(+)-patients (73.3%, 11/15) and non-pAKT(-)/pERK(+)-patients (29.5%, 13/44). After 2 weeks of sorafenib administration, the number of CTCs suffered a much sharper decline among pAKT(-)/pERK(+)-patients than non-pAKT(-)/pERK(+)-patients (P < 0.001). This decline was directly attributed to the reduction of pAKT(-)/pERK(+) CTCs. PFS was significantly correlated with the ratio of [pAKT(-)/pERK (+)]/total CTCs (r = 0.968, P < 0.001), while no significant correlation was observed with the number of pAKT(-)/pERK(+) CTCs (r = 0.491, P = 0.063). Moreover, PFS was significantly improved in patients with a ratio of [pAKT(-)/pERK(+)]/total CTCs ≥ 40% than that < 40%, of whom the median PFS was 8.4 m (95%CI: 4.8-12.0 m) and 1.3 m (95%CI: 1.2-1.4 m), respectively.

Conclusions

A high ratio of [pAKT(-)/pERK(+)]/total CTCs predicted longer PFS in HCC patients treated with sorafenib. These results suggest that the assessment of expression of pERK and pAKT in CTCs might provide important prognostic information for such patients.

Disclosure

All authors have declared no conflicts of interest.