ONCOLOGY UPDATE

Experts from the Dr Rosell Oncology Institute, co-authors of research presented at the European Cancer Congress (ECC) 2013

30/09/2013



Barcelona, September 2013. Experts from the Dr Rosell Oncology Institute (IOR), co-authors of research presented at the ECCO-ESMO-ESTRO European Cancer Congress (ECC) 2013 in Amsterdam. Results presented include analyses of predictive biomarkers and novel mechanisms of resistance to targeted therapies, as well as the early results of whole exome and transcriptome sequencing in collaboration with the US Cancer Therapeutics Innovation Group (GTIC). Results of the studies were presented during the congress in the form of oral presentations and posters.



Pooled analysis of the European (EUR) and Chinese (Ch) BRCA1-RAP80 Expression Customization (BREC) randomized trials of customized therapy in advanced non-small-cell lung cancer (NSCLC) patients (p) (NCT00617656/GECP-BREC and ChiCTR-TRC-12001860)

Rafael Rosell et al.

Abstract # 3.414 Poster discussion


The Spanish Lung Cancer Group and the French Lung Cancer Group performed a prospective, randomized phase III trial in metastatic NSCLC patients to compare non-customized cis/doc with customized therapy customized according to BRCA1 and RAP80 mRNA expression levels. The primary endpoint was progression-free survival (PFS). Based on the negative results for PFS at the interim analysis, accrual was closed on this study. The negative results may be due to the poor predictive capacity of RAP80 and/or to the inclusion of doc alone as a treatment in the experimental arm. Customized chemotherapy could be further encouraged in oncogene-driven pan-negative patients with PS 0.



Phase IB study to evaluate the efficacy and tolerability of olaparib (AZD2281) plus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation positive advanced non-small-cell lung cancer (NSCLC) patients (pts). (NCT=1513174/GECP-GOAL)

Rosario Garcia Campelo et al.

Abstract # 3420 Poster discussion


Progression-free survival (PFS) and response rate (RR) to EGFR tyrosine kinase inhibitors (TKIs) vary in pts with NSCLC driven by EGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. In our experience, high BRCA1 mRNA expression negatively influenced PFS among EGFR mutant pts treated with erlotinib. We hypothesized that since olaparib can attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve PFS in these pts. This phase IB trial of gefitinib plus olaparib confirms the tolerability of the combination and the activity seen warrants further exploration in treatment-naïve patients. A phase II randomized trial in treatment-naïve EGFR-mutant advanced NSCLC is planned in 2013.



MED12, a component of the transcriptional MEDIATOR complex, and STAT3 influence outcome to platinum-based chemotherapy in patients (p) with advanced non-small-cell lung cancer (NSCLC)

Daniela Morales-Espinosa et al.

Abstract # 3.514 Poster


MED12 negatively regulates TGF-β receptor signaling. Loss of MED12 induces an EMT-like phenotype associated with chemotherapy resistance. IDO and IL6 activate the JAK2/STAT3 signaling pathway, which – together with NFkB (RelA) signaling – is often altered in lung cancer. BIM could influence response to chemotherapy. We have examined these components and KRAS mutations in NSCLC tumor samples and correlated results with progression-free survival (PFS). There was no correlation between gene expression levels and KRAS mutation status. In the multivariate analysis, including gene expression levels, histology and PS, only MED12 and STAT3 were associated with PFS. None of the markers were associated with overall survival. To the best of our knowledge, this is the first time that low expression of MED12 has been correlated with significantly shorter PFS in NSCLC p receiving platinum-based chemotherapy. MED12 could be a new biomarker of chemoresistance and inhibition of TGF-βR signaling can restore chemotherapy response in patients with low MED12.



RAC1b mRNA expression and prognosis in advanced non-small cell lung cancer treated with first-line chemotherapy

Amaya Gascó et al.

Abstract # 652 Poster


Chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC) patients, except for those harboring EGFR mutations or EML4-ALK rearrangements. RAC1b, a RAC1 spliced variant, is over-expressed in NSCLC and impairs apoptosis by activation of nuclear-factor-ΚB. We evaluated the role of mRNA RAC1/RAC1b ratio as a predictor of chemotherapy efficacy in advanced NSCLC. We found a significant association with histology and rRAC1b, but no association between age, gender, mutational status and rRAC1b. When analyzed by tertiles, we found significantly poor median survival in SCC patients with higher rRAC1b but not in AD and LC subtypes. The multivariate regression analysis identified high rRAC1b as a poor prognostic marker for PFS in SCC. High rRAC1b constitutes a marker of poor PFS and OS in SCC of the lung treated with first-line chemotherapy.

 


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