NCCTG N0821 (Alliance): A Phase II First-Line Study of Pemetrexed, Carboplatin, and Bevacizumab in Elderly Patients with Advanced Nonsquamous Non–Small-Cell Lung Cancer With Good Performance Status

Abstract

We hypothesized that the combination of bevacizumab, carboplatin, and pemetrexed will be an effective first-line regimen in fit, elderly patients with nonsquamous non-small-cell lung cancer. Treatment-naïve, stage IIIB/IV nonsquamous non-small-cell lung cancer patients more than 70 years old with good performance status (Eastern Cooperative Oncology Group performance status 0-1) and adequate organ function were eligible. Carboplatin area under the curve 6, pemetrexed 500 mg/m, and bevacizumab 15 mg/kg were administered on day 1 of each 21-day cycle (up to six cycles) followed by maintenance pemetrexed and bevacizumab. The primary end point of 6-month progression-free survival rate of at least 70% was assessed using a one-stage binomial design. Quality of life (QOL) questionnaires were administered. Polymorphisms in genes encoding relevant proteins (drug targets, transport, and metabolism proteins) were correlated with treatment outcome. Fifty-seven eligible patients were enrolled. Median age was 74.5 years. Median treatment cycles received was 6. The most common grade 3 or higher non-hematologic adverse events were fatigue (26%) and hypertension (11%); 16% had grade 4 neutropenia and 6.5% had grade 4 thrombocytopenia. Three patients experienced grade 3/4 hemorrhagic events (one pulmonary, two gastrointestinal). Primary end point of PFS6 was 60% (95% confidence interval [CI]: 45.9-73%). Median PFS was 7.0 months (95% CI: 5.9-10.1), median overall survival was 13.7 months (95% CI: 9.4-16.8). Polymorphic KDR and VEGFA variants correlated with survival and toxicity, respectively. There was no significant change in overall QOL scores over time. This regimen is feasible and did not decrease the QOL in this study population. However, it did not meet the primary efficacy end point.