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I. Chaib



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      66P - PALB2 mRNA expression as a predictive marker in advanced non-small cell lung cancer (NSCLC) patients (p) treated with docetaxel-cisplatin (ID 405)

      12:30 - 13:00  |  Author(s): I. Chaib

      • Abstract
      • Slides

      Background:
      PALB2, the partner and localizer of BRCA2, binds directly to BRCA1 and is essential for homologous recombination repair and, henceforth, could influence the effect of docetaxel-cisplatin therapy. Previous studies have shown that PALB2 impedes the degradation of nuclear factor erythroid 2-related factor 2 (NRF2) through the binding and sequestration of its inhibitor Kelch-like ECH-associated protein (KEAP1). Over-expression of NRF2 could activate NOTCH signaling and lead to enrichment of cancer stem cells. In the current study, we examine the mRNA levels of PALB2 in advanced NSCLC p treated with docetaxel-cisplatin.

      Methods:
      We assessed PALB2 mRNA levels as potential biomarkers in tumor tissue from 177 cisplatin plus docetaxel-treated NSCLC p from the NCT00617656/GECP-BREC trial. The relationship of the PALB2 mRNA levels with the PFS, OS and response were examined.

      Results:
      Median age 62; 79.1% male; 51.4% adenocarcinoma. Results of PALB2 mRNA expression were as follows: PFS was 5.6 months (m) for p with high/intermediate (H-I) PALB2 and 4.1 m for p with low (L) PALB2 (p = 0.0018). OS was 13.2 m for p with H-I PALB2 compared to 9.9 for p with L PALB2 (p = 0.0377). In the univariate analysis, H-I PALB2 was a marker of longer PFS (HR = 0.56, 95% CI, 0.38, 0.80; p = 0.002) and OS (HR = 0.64, 95% CI, 0.41, 0.98; p = 0.0394). In the multivariate analysis, only H-I PALB2 was associated with longer PFS (here HR = 0.56 and p = 0.0022) and OS (HR = 0.61 and p = 0.0343). Among 143 p with data for response and PALB2 expression, 49.5% of p with H-I PALB2 were responders, compared to only 28% with L PALB2 (p = 0.0131).

      Conclusions:
      Higher PALB2 mRNA levels were associated with higher response, longer PFS and OS in NSCLC p treated with docetaxel-cisplatin. However, PALB2 could also be a readout of NRF2 activity and NOTCH signaling, indicative of an increase in cancer stem cells, providing hints for combinatory therapy with gamma secretase inhibitors to prevent the increase of stem-like cells and further improve outcome to docetaxel-cisplatin therapy. Experiments in NSCLC cell lines are ongoing.

      Clinical trial identification:


      Legal entity responsible for the study:
      IGTP, Germans Trias i Pujol Research Institute, Badalona, Barcelona, Spain

      Funding:
      Fundació Obra Social “La Caixa”

      Disclosure:
      All authors have declared no conflicts of interest.

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