1253P - A randomized phase II study of paclitaxel-carboplatin-bevacizumab (PCB) with or without nitroglycerin patches (NTG) in patients (pts) with stage IV...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Translational Research
Non-Small Cell Lung Cancer
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Anne-Marie Dingemans
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors A.C. Dingemans1, H.J.M. Groen2, G. Herder3, E.F. Smit4, S. Burgers5, J. Stigt6, P. De Goeije7, O. Dalesio8, B. Biesma9, V. van der Noort10, J.G. Aerts7
  • 1Pulmonology, Maastricht University Medical Center (MUMC), 6202 AZ - Maastricht/NL
  • 2Department Of Pulmonary Diseases, University Hospital Groningen (UMCG), NL-9700 RB - Groningen/NL
  • 3Pneumonoloy, St. Antonius Ziekenhuis, Nieuwegein/NL
  • 4Dept. Of Pulmonary Diseases, Vrije University Medical Centre (VUMC), NL-1081 HV - Amsterdam/NL
  • 5Pulmonary Diseases, Antoni van Leeuwenhoek Hospital, amsterdam/NL
  • 6Pulmonologie, isala, Zwolle/NL
  • 7Pulmonary Diseases, Amphia Hospital/Erasmus MC, 4818CK - Breda/NL
  • 8Statistics, netherlands cacner institue, amsterdam/NL
  • 9Pulmonary Diseases, Jeroen Bosche ziekenhuis, 's hertoghenbosch/NL
  • 10Biostatistics, Antoni van Leeuwenhoek Hospital, amsterdam/NL



NTG added to standard chemotherapy has been shown to improve clinical outcome. NTG is hypothesized to increase tumor blood flow and may augment drug delivery to the tumor and diminish tumor hypoxia causing a decrease in VEGF. High circulating VEGF is a prognostic factor for unfavourable outcome. We showed that adding NTG to PCB (PCB + N) did not improve progression free survival (PFS), response rate (RR) and overall survival (OS) in pts with stage IV NS-NSCLC (NCT01171170; Dingemans, ASCO 2014). Here we present impact of baseline VEGF on clinical outcome.


In this open-label multicenter phase II trial chemo-naive pts with stage IV NS-NSCLC were randomized 1:1 to PCB or PCB + N. Pts were treated with P 200 mg/m2 day (d) 1-C AUC 6 d1-B 15 mg/kg d1 every 3 weeks (wks) or PCB + NTG 15 mg/24 h for 5 d (d -2 to +3) every cycle for 4 cycles and B + N until progression. The study was powered (80%) to detect a decrease in the hazard of progression of 33% at α = 0.05 with a two-sided log rank test. As pre-planned exploratory analysis baseline, wks 3 and 6 free circulating VEGF levels by ELISA were assessed.


223 pts were randomized; 112 PCB and 111 PCB + N; Median (95% CI) PFS in PCB was 6.8 months (m) (5.6-7.3) and 5.0 m (4.2-5.8) in PCB + N, HR 1.22 (0.91-1.63). OS was 11.6 m (8.7-14) in PCB and 9.5 m (7.8-11.9) in PCB + N, HR 1.12 (0.76-1.67). Baseline median VEGF (n = 178) was 111 pg/ml (inter-quartile range 55-218), equal between 2 arms. High VEGF levels (n = 89) at baseline was associated with worse OS (p = 0.02) and PFS (p = 0.0003). For pts with above median VEGF at baseline, OS and PFS were not different for PCB and PCB + N, for pts with below median VEGF there was a trend for worse PFS HR 1.46 (0.95 – 2.24) and OS HR1.55 (0.97-2.49) in the pts treated with PCB + N. In both arms VEGF became undetectable or very low at 3 and 6 wks.


Adding NTG to first line PCB does not improve PFS and OS in pts with stage IV NS-NSCLC. As the mechanism of action of NTG is presumably through the VEGF pathway, decrease of VEGF levels by B may preclude an additional effect of NTG.


A.C. Dingemans: advisory board Roche; H.J.M. Groen: advisory board roche E.F. Smit: advisory board roche; J.G. Aerts: advisory board roche. All other authors have declared no conflicts of interest.