A multicenter, randomized phase II study of sequential vinorelbine (V)/cisplatin (C)/bevacizumab (B) followed by docetaxel (D)/gemcitabine (G)/B versus D/C/B as a first-line therapy for advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).

Abstract

e18105 Background: The combination of D with G has been shown equally active compared to the platinum-based doublets, which is considered the cornerstone for the treatment of NSCLC, with a more favorable toxicity profile (Georgoulias V. Lancet 2001 357: 1478-84). Sequential therapy with four active drugs (two doublets) in NSCLC, including C, was recently investigated and attributed a promising response rate (Pallis A. Lung Cancer, 2006, 52(2): 165-71). Incorporation of B to the standard platinum-based regimen improved its clinical outcome. Aim of this trial was to compare the efficacy of sequential four drug treatment in combination with B to the standard non platinum-based regimen combined with B. Methods: Seventy-seven treatment naïve patients (pts) with stage IIIB and IV non-squamous NSCLC were randomized to receive V 60 mg/m2 PO on day 1 and 8, C 80mg/m2 IV on day 1 and B 15 mg/kg IVon day 1, for 3 cycles followed by D 75 mg/m2 IV, G 1100 mg/m2 IV and B 15 mg/kg IV, all on day 1 (Arm A) or D 75 mg/m2 IV, C 80mg/m2 IV and B 15 mg/kg IV on day. The cycles were repeated every 3 weeks for a total of 6 cycles. The primary endpoint of the study was response rate (RR) and the secondary outcome measures were overall survival (OS) and progression free survival (PFS). Results: Thirty-nine pts were randomized to the control arm (Arm B) and 38 pts to the sequential arm. Pt demographics were balanced in both the arms. The overall RR was 36.8% and 46.2% in arm A and B, respectively (p= 0.49). There were 3 complete responses, one in arm A. Median PFS was 6.87 and 5.53 months in arm A and B, respectively (p= 0.368). Median OS was 19.6 and 10.33, respectively (p= 0.239). The estimated 1 and 2-year survival for arm A versus B were 71.1% and 36% versus 45.3% and 28%, respectively. No statistically significant difference in the toxicity profile was observed between the 2 arms. Conclusions: Sequential treatment with four active drugs is feasible and safe. The combination attributes encouraging results compared to the standard platinum-based regimen.