77P - Glycolytic marker monocarboxylate transporter 4 (MCT4) and outcome to bevacizumab (bev): An exploratory analysis in advanced non-small cell lung ca...

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Cytotoxic agents
Translational Research
Non-small-cell lung cancer
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological therapy
Presenter Laura Bonanno
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors L. Bonanno1, F. Calabrese2, A. De Paoli3, G. Pasello1, A. Santo4, A. Favaretto5, M. Chilosi6, A. Del Conte7, P.F. Conte8, S. Indraccolo9
  • 1Medical Oncology 2, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 2Department Of Cardiothoracic And Vascular Sciences, Università degli Studi di Padova, 35128 - Padova/IT
  • 3Clinical Trials And Biostatistics Unit, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 4Medical Oncology, Azienda Ospedaliera Universitaria Integrata, 37126 - Verona/IT
  • 5Medical Oncology, Ospedale Regionale Treviso, Treviso/IT
  • 6Pathology And Diagnostics, Università degli Studi di Verona, Verona/IT
  • 7Medical Oncology, Ospedale S. Maria degli Angeli, 33170 - Pordenone/IT
  • 8Surgery,oncology And Gastroenterology, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 9Immunology And Molecular Oncology, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT

Abstract

Background

Platinum-based chemotherapy (CT) is the mainstay of non oncogene-addicted A-NSCLC therapy with the option of adding bev in clinically selected patients (pts). Preclinical data indicate potential effects of increased glycolytic activity on response to antiangiogenesis. MCT4 is a trans-membrane lactate transporter and is a marker of glycolytic activity.

Methods

We retrospectively analyzed 125 A-NSCLCs treated with first-line platinum-based CT with/without bev. MCT4 protein expression was analyzed by immunohistochemistry. Univariate and multivariate analysis was performed to evaluate the impact of MCT4 on outcome in pts treated with/without bev.

Results

The median overall survival (OS) was 11.7 (95% CI: 9.1–15.3) months (m), the median progression free survival (PFS) was 6.7 (95% CI: 5.7–7.2) m and the response rate was 43%. Pts receiving bev were 42 (34%). MCT4 quantification was feasible in 82 (64%) cases, 28 (34%) of them were treated with bev. The impact of bev on OS and PFS found by univariate analysis was not confirmed by multivariate analysis in the study population. MCT4 expression was considered as categorical variable, dividing the population into 2 groups: tumors with high levels of MCT4 (score >15) and tumors with null/low expression (score 0–15). MCT4 expression did not affect the outcome of the 82 pts but, re-classifying them according to treatment, a differential impact of MCT4 on outcome was noticed. Among pts receiving only CT, those expressing high MCT4 achieved a median OS of 5 (95% CI: 3.2–6.4) m versus a median OS of 11.5 (95% CI: 6.3–17.4) m in the presence of null/low MCT4 (p: 0.04). The HR was 2.1 (95% CI: 1.1–4.4) and the prognostic value was confirmed by multivariate analysis. In the CT plus bev group no effect of MCT4 on outcome was observed.

Conclusions

High MCT4 expression has negative prognostic value only in pts treated with CT without bev, generating the hypothesis that bev could reverse the negative effect of increased glycolytic activity. Pts with highly glycolytic tumors might have increased benefit from bev. The results warrant further confirmation in larger retrospective cohorts with genetic profiling and prospective validation.

Clinical trial identification

Legal entity responsible for the study

Istituto Oncologico Veneto

Funding

Istituto Oncologico Veneto

Disclosure

All authors have declared no conflicts of interest.