High insulin-like growth factor 1 receptor (IGF1R) expression is associated with poor survival in surgically treated non-small cell lung cancer (NSCLC) patients (pts)

Abstract

7550 Background: IGF1R represents a novel molecular target in NSCLC. We aimed to evaluate the association between IGF1R expression, clinical characteristics and survival in operable NSCLC pts. Methods: 184 consecutive surgically treated pts (median follow up of 32 months [range: 13–51 months]) were included in the study. There were 23% females, 55% pts with squamous cell carcinoma, 28% with adenocarcinoma, 3% with large cell carcinoma, 13% with mixed carcinoma and 1% with other types, 5% were never-smokers. Median age was 64 years (range: 37–85 years). Pathological stage I was diagnosed in 41%, stage II –22%, stage III –33% and stage IV –4% pts. Induction or adjuvant treatment was not routinely used. IGF1R was evaluated in tissue microarray by immunohistochemistry and scored by two observers according to H-score, taking into account proportion of cells with positive staining times staining intensity (scale 0–400). Results: IGF1R IHC expression was low in analyzed samples (median H-score 20, range: 0–223). Higher IGF1R score was observed in adenocarcinomas vs. squamous-cell carcinomas (p=0.02) and never-smokers vs. smokers (p=0.02). IGF1R score did not depend on stage (p=0.98) and sex (p=0.83). When analyzed as a continuous variable, IGF1R score tended to associate with worse survival in the entire cohort (p=0.10), and was significantly associated with inferior survival in patients with complete (R0) resections (p=0.04). When categorized with cut-off point of 50 (30% of patients positive), IGF1R expression was again associated with poor survival (p=0.05). This association was confined to pathological stage I (hazard ratio, HR=3.07; 95% confidence interval, CI=1.41–6.70, p=0.005) vs. all other stages (HR=1.03; 95% CI=0.63–1.70, p=0.90), and to patients with adenocarcinoma histology (HR=2.67; 95%CI=1.17–6.70, p=0.02 vs. all other histologies (HR=1.28; 95%CI=0.79–2.11, p=0.32). Conclusion: In this cohort of operable NSCLC pts, high IGF1R expression was associated with never-smoking history, adenocarcinoma histology, and poor survival, particularly in stage I disease and in patients with adenocarcinoma. These results support involvement of IGF pathway in the progression of early-stage NSCLC. No significant financial relationships to disclose.

High Expression Levels of Total IGF-1R and Sensitivity of NSCLC Cells In Vitro to an Anti-IGF-1R Antibody (R1507)

“…Conversely, high plasma levels of IGFBP3 have been associated with reduced risk [10] . High IGF-1R expression is associated with poor survival in surgically treated NSCLC patients [11] . In a recent randomized phase II trial involving patients with stage IIIB, IV, or recurrent, treatment-naïve NSCLC, addition of an anti-IGF-1R antibody (CP-751,871; Pfizer) to standard chemotherapy (paclitaxel and carboplatin) led to a 46% objective response rate versus a 32% rate in patients receiving chemotherapy alone [12] .…”

Update in Lung Cancer 2008

“…The role of the insulin-like growth factor receptor (IGFR) pathway in lung cancer has recently been established. The insulin-like growth factors IGF-1 and IGF-2 and their receptor IGF-1R are overexpressed in NSCLC (111) and IGF-1R expression is associated with worse prognosis in patients with sur-gically resected disease (112). The IGF-1R monoclonal antibody CP-751,871 in combination with carboplatin/paclitaxel was compared with chemotherapy alone in a randomized phase II study of treatment-naive patients with advanced NSCLC (113).…”

Impact Study: MK-0646 (Dalotuzumab), Insulin Growth Factor 1 Receptor Antibody Combined with Pemetrexed and Cisplatin in Stage IV Metastatic Non-squamous Lung Cancer

“…Increased expression of IGFBP-3 is associated with improved outcome in resected stage I lung cancer ( 3 ). High expression of IGF-1R is associated with poor survival in surgically resected stage I adenocarcinoma which along with never-smokers had a higher expression of IGF-1R compared to squamous histology or smokers ( 4 ). Low IGF-1R expression was associated with significant improvement in survival in adenocarcinoma, while there was no correlation between IGF-1R expression and survival in patients with squamous histology.…”