Protein deletion predicts length of progression free survival (PFS) in patients with non-small cell lung cancer (NSCLC)
Deletion of the Bcl-2-like protein 11 (BIM) in advanced non-small cell lung cancer (NSCLC) is associated with shorter progression free survival (PFS). This was found in Asian patients who had been treated either with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) or chemotherapy. Also, BIM deletion independently predicts overall survival (OS) of patients with advanced NSCLC.
The BIM protein can activate the programmed cell death known as the apoptotic pathway in cells. BIM deletion has been detected in 12.8% of the Asian population but is very rarely observed in the white population. All NSCLC patients treated with any therapy, targeted or chemotherapeutic, ultimately fail their therapy but at varying times.
Researchers at the National Taiwan University Hospital examined the impact of BIM deletion on the survival outcomes of 204 patients with advanced NSCLC treated with either EGFR TKIs or chemotherapy.
Results were reported in the Journal of Thoracic Oncology (2014; doi:10.1097/JTO.0000000000000238). The data indicated that BIM deletion was an independent predictive factor for shorter PFS in patients treated with EGFR TKI (hazard ratio=2.15, P=.002) with a median PFS of 4.6 months in patients with BIM deletion versus 8.6 months in patients with wild type. Similar results were observed in chemotherapy-treated patients with a hazard ratio of 2.4 (P=0.016) and median PFS of 3.5 and 5.6 months in deletion versus wild type, respectively. Overall survival was also independently predicted by BIM deletion (hazard ratio=1.65, P=0.039).
“Our findings suggest the BIM deletion polymorphism should be considered as a clinical trial stratification factor when systemic treatment is considered in Asian NSCLC patients,” said senior author James Chih-Hsin Yang, MD, PhD, of National Taiwan University Hospital. He added, “Since little is known about whether anti-apoptotic agents are able to overcome the resistance to EGFR TKIs resulting from BIM deletion, it may be warranted to explore anti-apoptotic agents, such as obatoclax, in future clinical trials.”