Journal Article

Clinical usefulness of PI3K/Akt/mTOR genotyping in companion with other clinical variables in metastatic renal cell carcinoma patients treated with everolimus in the second and subsequent lines

L. Bodnar, R. Stec, S. Cierniak, A. Synowiec, G. Wcisło, M. Jesiotr, R. Koktysz, W. Kozłowski and C. Szczylik

in Annals of Oncology

Published on behalf of European Society for Medical Oncology

Volume 26, issue 7, pages 1385-1389
Published in print July 2015 | ISSN: 0923-7534
Published online May 2015 | e-ISSN: 1569-8041 | DOI: https://dx.doi.org/10.1093/annonc/mdv166
Clinical usefulness of PI3K/Akt/mTOR genotyping in companion with other clinical variables in metastatic renal cell carcinoma patients treated with everolimus in the second and subsequent lines

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Background

The aim of this study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of PI3K/AKT/mTOR pathway.

Patients and methods

In a prospective, one-arm, phase II study, patients with mRCC received everolimus (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential biomarkers of PI3K/AKT/mTOR pathway.

Results

The median age of the 58 patients enrolled into the study was 60 years (range 41–78 years). In multivariate analysis, it was found that the adverse independent predictors for everolimus therapy were histological grade G1/2 {hazard ratio (HR): 2.68 [95% confidence interval (CI) 1.29–5.58, P = 0.0082]}, increased lactate dehydrogenase (LDH) level before treatment [HR: 2.55 (95% CI 1.30–4.99, P = 0.0064)] and the PIK3CA gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11–3.89, P = 0.0254). In multivariate analysis, it was observed that the adverse independent prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 1.66–10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA versus CC = 1.97 (95% CI 1.02–3.79; P = 0.0421)].

Conclusions

The PI3KCA gene polymorphism, LDH, and histologic grade can predict the effects of everolimus treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may be independent prognostic factors. Further investigation is needed to confirm and validate these findings prospectively in other RCC trials.

Keywords: renal cell carcinoma; everolimus; mTOR; PI3KCA; AKT

Journal Article.  3554 words.  Illustrated.

Subjects: Medical Oncology

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