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Assessment of efficacy of adjuvant chemotherapy for non-small cell lung cancer with metastatic ability involving ACTN4

Date

08 Oct 2016

Session

Poster Display

Presenters

Kazufumi Honda

Citation

Annals of Oncology (2016) 27 (6): 407-410. 10.1093/annonc/mdw381

Authors

K. Honda1, N. Miura2, H. Shiraishi3, K. Onidani2, H. Shoji2, T. Yamada1, Y. Fujiwara3, Y. Ohe4

Author affiliations

  • 1 Division Of Chemotherapy And Clinical Research, National Cancer Center Reseach Institute, 104-0045 - Tokyo/JP
  • 2 Division Of Chemotherapy And Clinical Research, National Cancer Center Reseach Institute, Tokyo/JP
  • 3 Department Of Thoracic Oncology, National Cancer Center Hospital, Tokyo/JP
  • 4 Department Of Thoracic Oncology, National Cancer Center Hospital, 1040045 - Tokyo/JP
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Resources

Abstract 1392

Background

Selection of patients with high metastatic ability of non-small cell lung cancer (NSCLC) has the potential to predict the clinical benefit of adjuvant chemotherapy (ADC). ACTN4 is an oncogene associated with cancer metastasis. To demonstrate the clinical utility of a predictive biomarker for the efficacy of ADC for NSCLC, we analyzed clinical and preclinical data.

Methods

In Step 1, we reanalyzed the impact of ACTN4 on the efficacy of ADC from clinical information and mRNA profiles from the public database of a randomized phase III trial of adjuvant vinorelbine plus cisplatin after complete resection of stage IB or II NSCLC (JBR.10), which was a clinical trial probing the clinical benefits of ADC in stage IB/II patients with NSCLC. In Step 2, we measured ACTN4 protein levels in patients with completely resected stage II or IIIA lung adenocarcinoma at the National Cancer Center Hospital (NCCH) from 2008 to 2011 using immunohistochemistry (IHC). We then retrospectively compared survival between ADC treated with platinum doublet and observation (OBS) groups. In Step 3, we investigated the biological functions of ACTN4 with the A549 lung adenocarcinoma cell line, which has gene amplification of ACTN4.

Results

In Step 1, the 133 patients enrolled in JBR.10 were divided into two groups by expression of the ACTN4 transcript: an ACTN4-positive (ACTN4(+)) group (n = 25) and an ACTN4-negative (ACTN4(-)) group (n = 108). In the ACTN4(+) group, overall survival (OS) was significantly longer in ADC subjects (n = 15) compared with OBS (n = 10) (hazard ratio [HR] = 0.27; p = 0.042). However, no differences in OS were noted between ADC (n = 56) and OBS (n = 52) subjects in the ACTN4(-) group. In Step 2, 148 eligible patients were classified into two groups based on IHC findings. In the ACTN4-IHC(+) group (n = 75), mean survival was longer in the ADC patients (n = 22) than in OBS patients (n = 53) (HR = 0.307; p = 0.028). In contrast, the ACTN4-IHC(-) group (n = 73) showed no tangible survival benefit with ADC. In Step 3, the metastatic potential of A549 was significantly reduced by ACTN4 shRNA.

Conclusions

Clinical data and biological assays suggested ACTN4 as a potential predictive biomarker for the efficacy of ADC in patients with NSCLC.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

AMED

Disclosure

All authors have declared no conflicts of interest.

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