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Association of PALB2 Messenger RNA Expression with Platinum-Docetaxel Efficacy in Advanced Non-Small Cell Lung Cancer
Niki Karachaliou1, Jillian Wilhelmina Paulina Bracht2, Manuel Fernandez Bruno3
1Institute of Oncology Rosell, University Hospital Sagrat Cor, QuironSalud Group, Barcelona, Spain; Pangaea Oncology, Laboratory of Molecular Biology, Quiron-Dexeus University Institute, Barcelona, Spain.
Introduction:
Partner and localizer of BRCA2 (PALB2) is essential for homologous recombination repair. We examined mRNA levels of DNA repair genes, including partner and localizer of BRCA2 gene (PALB2), ring finger protein 8 gene (RNF8), replication timing regulatory factor 1 gene (RIF1), ATM serine/threonine kinase gene (ATM), and tumor protein p53 binding protein 1 gene (53BP1) as predictive biomarkers for cisplatin-docetaxel in the European phase III BRCA1, DNA repair associated (BRCA1)-receptor-associated protein 80 (RAP80) expression customization (BREC) phase III clinical trial (ClinicalTrials.gov identifier NCT00617656).
Methods:
The study was a prespecified secondary objective of the BREC trial. We assessed mRNA levels of PALB2 and four more DNA repair genes (RNF8, RIF1, ATM and 53BP1) as biomarkers in tissue from 177 patients with cisplatin-docetaxel-treated NSCLC. We examined the relationship of gene expression levels with progression-free survival, overall survival, and response.
Results:
In 177 patients with NSCLC (who had a median age of 62 years and included 140 men and 91 patients with adenocarcinoma), only high PALB2 mRNA expression was predictive in the progression-free survival Cox regression analysis (hazard ratio = 0.63, 95% confidence interval: 0.42-0.83, p = 0.0080). PALB2 was also predictive of overall survival (hazard ratio = 0.68, 95% confidence interval: 0.42-0.90, p = 0.0266). Among the 158 patients evaluable for response, high PALB2 mRNA expression was predictive of response to cisplatin-docetaxel. Specifically, an objective response rate of 77% to cisplatin-docetaxel was observed for patients with high PALB2 mRNA expression compared with a rate of only 23 % for those with low PALB2 mRNA expression (p = 0.0448).
Conclusions:
High PALB2 mRNA expression identified patients with NSCLC who significantly benefited from cisplatin-docetaxel chemotherapy in the European BREC phase III clinical trial. The combination of chemotherapy with immunotherapy will become the standard of care, and a predictive marker of response to chemotherapy may accurately guide therapeutic decision making.
Insights
High partner and localizer of BRCA2 (PALB2) mRNA expression predicts better outcomes for non-small cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel. This finding identifies PALB2 as a key biomarker for guiding chemotherapy decisions in NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Partner and localizer of BRCA2 (PALB2) is crucial for DNA repair via homologous recombination.
- Biomarkers are needed to predict treatment response in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To evaluate mRNA levels of DNA repair genes, including PALB2, as predictive biomarkers for cisplatin-docetaxel chemotherapy in NSCLC patients.
- To assess the relationship between gene expression and clinical outcomes in the European BREC phase III trial.
Main Methods:
- Retrospective analysis of mRNA expression of PALB2, RNF8, RIF1, ATM, and 53BP1 in tumor tissue from 177 NSCLC patients.
- Correlation of gene expression levels with progression-free survival, overall survival, and treatment response.
Main Results:
- High PALB2 mRNA expression was significantly associated with improved progression-free survival (HR=0.63, p=0.0080) and overall survival (HR=0.68, p=0.0266).
- Patients with high PALB2 expression showed a higher objective response rate (77%) to cisplatin-docetaxel compared to those with low expression (23%, p=0.0448).
Conclusions:
- High PALB2 mRNA expression is a predictive biomarker for benefit from cisplatin-docetaxel chemotherapy in NSCLC.
- PALB2 may guide therapeutic decisions in NSCLC treatment, potentially in combination with immunotherapy.
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