7567 Background: Third-line treatment option for advanced NSCLC patients is very limited with a lack of effective drugs and specific trials targeting this patient population. V+B combination was previously investigated in a phase I study at our institution, which suggested anti-tumor activity in NSCLC. We conducted this phase II trial to evaluate the efficacy and tolerability of this combination as third-line therapy in advanced NSCLC.
METHODS
Eligibility included: recurrent/metastatic NSCLC, receiving 2 prior systemic regimens, and performance status 0-2. Stable, treated brain metastasis was allowed. Patients received V 400 mg PO daily D1-14 and B 1.3 mg/m2 IV D1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS). Secondary endpoints were response, survival, toxicity, B-induced neuropathy, and correlates. This study followed two-stage minimax design (n=18+15=33).
RESULTS
From 01/2009 to 03/2010, 18 patients were enrolled in the first stage. Median age was 59; half were women. Histology included adenocarcinoma (50%), NSCLC-NOS (33%) and squamous cell (17%). All patients had platinum-based doublets involving taxane or pemetrexed as first-line treatment. Second-line therapy included pemetrexed (50%), erlotinib (22%), or other agents (28%). Patients received a median of 2 treatment cycles (range: 1-6). The most common reason for treatment discontinuation was disease progression. Efficacy results: median PFS was 1.43 months (95% CI 1.15-2); 3m-PFS 13% (95% CI 0-0.294); and median overall survival 4.7 months (95% CI 3.15-8.64). There was no response; stable disease was observed in 5 patients (28%). Most common grade 3/4 toxicities were: thrombocytopenia (8/1), lymphopenia (3/1), and fatigue (5/1). Grade 3 peripheral sensory neuropathy was seen in 1 patient.
CONCLUSIONS
This phase II trial demonstrated that V+B combination was well tolerated in this patient population. However, due to lack of efficacy observed in the first stage, the study was terminated. Analysis results of histone acetylation, p21, HSP70 gene expression, and 20S proteasome inhibition will be presented at the time of the meeting.