A Prospective Randomized Open Label Phase III Study of Maintenance Gemcitabine Versus Best Supportive Care Following Platinum-Paclitaxel Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer

Abstract

Aim: Approximately two‐thirds of all patients with newly diagnosed non‐small‐cell lung cancer (NSCLC) have advanced disease (stage IIIB or IV) that is only amenable to palliative chemotherapy. Switch maintenance therapy with a different active agent aims to hit clonal variants resistant to the first‐line therapy before they have had time to increase in number. Based on this, we conducted a randomized phase III study to compare Gemcitabine (G) versus Best Supportive Care (BSC) as maintenance therapy for patients with advanced NSCLC. Methods: Between July 2011 and January 2012, chemo‐naive patients with stage IIIB/ IV NSCLC were initially treated with six cycles of cisplatin (40 mg/m2 day 1, 2) and paclitaxel (175 mg/m2 day 1) every 3 weeks. Subsequently, non‐progressors were randomized 1:1 to receive maintenance G (1000 mg/m2 on days 1 and 8 every 3 weeks) or BSC alone till disease progression. The primary endpoint was the comparison of overall survival (OS) between the two arms and the secondary endpoint was progression free survival (PFS). The survival analyses were performed by using SPSS version 20.0. Results: 134 patients were enrolled (median age: 50 years, males 76.8%, stage IV disease 50.7%, ECOG performance status 0/1: 67.9%). Following 6 cycles of initial therapy, the RR was 35.1% (CR‐3%, PR‐32.1%), and 38.8% had SD. 99 non‐progressors were randomized to receive G (n = 50) or BSC (n = 49). The median OS for G was 10 months (95% CI: 9.2‐10.7) and 8 months (95% CI: 6.7‐9.2) for BSC, with a hazard ratio (HR) 0.64 (95% CI: 0.51‐0.77, P = 0.002). The median PFS was 9 months (95% CI: 8.1‐9.9) for G versus 7 months (95% CI: 6.3‐7.7) for BSC, with a HR 0.67 (95% CI: 0.50‐0.84, P = 0.009). Maintenance therapy was tolerated well despite a higher incidence of grade 3/4 toxicity (anemia 12% vs. 8.1%; neutropenia 18% vs. 4.1%; thrombocytopenia 14% vs. 2%; and fatigue 8% vs. 2%).