Maintenance gemcitabine versus best supportive care following platinum-paclitaxel chemotherapy for patients with advanced nonsmall cell lung cancer

Background: Approximately two-thirds of all patients with newly diagnosed nonsmall 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 (Gem) versus best supportive care (BSC) as maintenance therapy. 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, nonprogressors 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 a comparison of overall survival (OS) between two arms, and the secondary endpoint was progression-free survival (PFS). Results: Exactly 134 patients were enrolled (median age: 50 years, males 76.8%, Stage IV disease 50.7%, Eastern Cooperative Oncology Group performance status 0/1: 67.9%). Following 6 cycles of initial therapy, the Response Rate (RR) was 35.1% (Complete Response (CR) 3%, Partial Response (PR) 32.1%), and 38.8% had stable disease. Ninety-nine nonprogressors were randomized to receive Gem (n = 50) or BSC (n = 49). The median OS for Gem was 10 months (95% confidence interval [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%). Conclusion: Switch maintenance therapy with gemcitabine, following initial platinum-based doublet chemotherapy in advanced NSCLC can produce significantly longer PFS and OS compared to BSC alone at the cost of higher grade 3/4 hematological toxicities.