P2.03a-007 Pem/CBP/Bev Followed by Pem/Bev in Hispanic Patients with NSCLC: Outcomes According to Combined Score of TS, ERCC1 and VEGF Expression

Abstract

To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS), ERCC1 and VEGF mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance pemetrexed and bevacizumab was administered until disease progression or unacceptable toxicity. One hundred forty-four Hispanic patients with a median follow-up of 13.8 months and a median number of maintenance cycles of 6 (range, 1- 32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median progression-free and overall survival (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. Median TS, ERCC1 and VEGF mRNA levels were 1.45 (range, 0.17–2.52), 0.58 (range, 0.44-1.20), and 2.72 (range, 1.84-3.21), respectively. OS was significantly higher in patients with the lowest TS mRNA levels [29.6 months (95% CI 26.2-32.9) compared with those with higher levels 9.3 months (95% CI 6.6-12.0); p=0.0001]. ERCC1 mRNA levels also influenced the OS [median for ERCC1 mRNA˂0.58 28.7 months (95% CI 26.3-31.2) vs. ERCC1 mRNA˃0.58 11.1 months (95% CI 9.6-12.7); p=0.0001] as well as VEGF mRNA levels [median OS for VEGF mRNA˂2.72 26.4 months (95% CI 22.8-30.0) vs. VEGF mRNA˃2.72 18.2 months (95% CI 8.4-27.9); p=0.009]. TS mRNA did not influence treatment response, however the ORR was significantly higher in patients with low levels of ERCC1 (p = 0.003) and elevated VEGF (p = 0.005). Multivariate analysis found that TS mRNA levels (p=0.0001), VEGF mRNA levels (p=0.007) and PS (p=0.014) were independent prognostic factors. Overall, PCB followed by maintenance pemetrexed and bevacizumab was in Hispanic patients with non-squamous NSCLC. This regimen was associated with prolonged OS, particularly in patients with low TS, ERCC1 and VEGF mRNA expression. These biomarkers alone or in combination may be useful to assess the prognosis of patients with NSCLC treated with CBP/Pem/Bev.