Final Results of a Randomized, Double-Blind Phase II Study to Compare Nitroglycerin (N) Plus Oral Vinorelbine (NVBO) Plus Cisplatin (C) with Placebo (P) Plus NVBO Plus C in Patients (Pts) with Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC)

ABSTRACT Background Yasuda (JCO 2006) reported increased ORR, TTP and OS when adding N to the combination of i.v. vinorelbine (NVBiv) + C in pts with stage IIIB/IV NSCLC probably due to better drug delivery based on changed vascular tonus. NVBo and NVBiv have comparable efficacy with a more convenient administration of the oral form. Main study objective was the confirmation of the Asian results in a Caucasian population. Methods In the experimental arm pts received N 25 mg D-3 to D2 + NVBo (60) 80 mg/m2 D1, D8 + C 80 mg/m2 D1, q3w; in the control arm pts received P D-3 to D2 + NVBo (60) 80 mg/m2 D1, D8 + C 80 mg/m2 D1, q3w. Treatment continued until PD, unacceptable toxicity (tox) or pts wish to discontinue treatment. The primary endpoint was ORR, secondary endpoints included OS, PFS and safety. To show an ORR-increase from 40 to 70% with a power of 0.80 and a two-side alpha of 0.05 the planned sample size was 100 pts. Results From 10/07 to 05/10, 68 pts were randomised to the N-arm (35 pts) or P-arm (33 pts). 66 pts were treated (N-arm: 34 pts, P-arm: 32 pts). The study was stopped prematurely due to lack of recruitment. N-arm n = 34 P-arm n = 32 All n = 66 Male (%) 76.5 68.8 72.7 Median age (y, range) 63.0 (36-82) 62.5 (33-73) 62.5 (33-82) Median Karnofsky (%, range) 90 (70-100) 90 (70-100) 90 (70-100) Smoker (%) non/former/current 8.8/41.2/50.0 15.6/40.6/43.8 12.1/40.9/47.0 Squamous/adeno (%) 55.9/44.1 46.9/34.4 51.5/39.4 IIIB/IV/local relapse (%) 32.4/64.7/2.7 34.4/65.6/0 33.3/65.2/1.5 Median N cycles (n, range) 4.5 (1-8) 4.0 (1-6) 4.0 (1-8) ORR ITT (%) 95%CI 35.3 (19.7-53.5) 18.8 (7.2-36.4) 27.3 p = 0.171 ORR eval (%) 95%CI (n = 32/27/59) 37.5 (21.1-56.3) 22.2 (8.6-42.3) 30.5 p = 0.262 DCR ITT (%) 61.8 53.1 57.6 Median TTP (mo) 4.7 5.0 4.8 Median OS (mo) 11.0 12.1 11.5 Tox G3-4 u003e5% (%pts): N-arm: neutropenia 32.3, leucopenia 20.6, anemia 14.7, nausea 8.8 (G3), fatigue 5.9 (G3), pneumonia 5.9 (G3). P-arm: neutropenia 43.8, leucopenia 25.0, fatigue 9.4 (G3), nausea 9.4 (G3), anemia 6.3, vomiting 6.3. 1 case of febrile neutropenia G3 (N-arm). 2 deaths potentially related to chemotherapy (1 per arm). Conclusions The oral formulation of Vinorelbine + C achieved in both arms a high level of efficacy (all pts: ORR 27.3, DCR 57.6, TTP 4.8, OS 11.5). Despite the premature discontinuation and low sample size per group, the results seem to confirm previous data reported in Asian patients, with an ORR numerically higher in the N-arm but without significance. Disclosure M. Reck: Honoraria for lectures: Lilly, Roche, AstraZeneca, Daiichi-Sankyo Advisory Board: Lilly, Roche, AstraZeneca, Daiichi-Sankyo, BMS, Pfizer, Genentech. C. Rose: Employed by Pierre Fabre Pharma GmbH. All other authors have declared no conflicts of interest.