pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104
| العنوان: | pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104 |
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| المؤلفون: | Ormanns, Steffen, Siveke, Jens, Heinemann, Volker, Haas, Michael L., Sipos, Bence, Schlitter, Anna Melissa Elissa, Esposito, Iréne, Jung, Andreas, Laubender, Rüdiger Paul Aul, Kruger, Stephan, Vehling-Kaiser, Ursula, Winkelmann, Cornelia, Fischer von Weikersthal, Ludwig, Clemens, Michael Roland, Gauler, Thomas, Märten, Angela, Geissler, Michael, Greten, Tim F., Kirchner, Thomas, Boeck, Stefan |
| المصدر: | BMC Cancer |
| بيانات النشر: | Springer Nature |
| مصطلحات موضوعية: | Adult, Male, Cancer Research, EGFR, Medizin, Biomarker, Pancreatic cancer, Middle Aged, Survival Analysis, Pancreatic Neoplasms, Erlotinib Hydrochloride, Young Adult, eIF-2 Kinase, Erlotinib, Oncology, Biomarkers, Tumor, Quinazolines, Genetics, Humans, Female, Phosphorylation, Tumor Suppressor Protein p53, Extracellular Signal-Regulated MAP Kinases, Proto-Oncogene Proteins c-akt, Research Article |
| الوصف: | Background The role of pERK, pAKT and p53 as biomarkers in patients with advanced pancreatic cancer has not yet been defined. Methods Within the phase III study AIO-PK0104 281 patients with advanced pancreatic cancer received an erlotinib-based 1st-line regimen. Archival tissue from 153 patients was available for central immunohistochemistry staining for pERK, pAKT and p53. Within a subgroup analysis, biomarker data were correlated with efficacy endpoints and skin rash using a Cox regression model. Results Fifty-five out of 153 patients were classified as pERKlow and 98 patients as pERKhigh; median overall survival (OS) was 6.2 months and 5.7 months, respectively (HR 1.29, p = 0.16). When analysing pERK as continuous variable, the pERK score was significantly associated with OS (HR 1.06, 95% CI 1.0-1.12, p = 0.05). Twenty-one of 35 patients were pAKTlow and 14/35 pAKThigh with a corresponding median OS of 6.4 months and 6.8 months, respectively (HR 1.03, p = 0.93). Four out of 50 patients had a complete loss of p53 expression, 20 patients a regular expression and 26 patients had tumors with p53 overexpression. The p53 status had no impact on OS (p = 0.91); however, a significant improvement in progression-free survival (PFS) (6.0 vs 1.8 months, HR 0.24, p = 0.02) and a higher rate of skin rash (84% vs 25%, p = 0.02) was observed for patients with a regular p53 expression compared to patients with a complete loss of p53. Conclusion pERK expression may have an impact on OS in erlotinib-treated patients with advanced pancreatic cancer; p53 should be further investigated for its potential role as a predictive marker for PFS and skin rash. Trial registration NCT00440167 (registration date: February 22, 2007). Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-624) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1471-2407 0044-0167 |
| DOI: | 10.1186/1471-2407-14-624 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::e4012c00acd2e219498c925ef594cde7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....e4012c00acd2e219498c925ef594cde7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712407 00440167 |
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| DOI: | 10.1186/1471-2407-14-624 |