1245P - A Phase 3 randomised trial of adding nitroglycerin to first line chemotherapy for advanced non-small cell lung cancer: The Australasian Lung cancer...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cytotoxic agents
Non-small-cell lung cancer
Therapy
Biological therapy
Presenter Andrew Davidson
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors A. Davidson1, A.S. Veillard2, A. Tognela3, M.M.K. Chan3, K. Briscoe4, B. Hughes5, M. Boyer6, S. Begbie7, N. Muljadi2, X. Coskinas2, S. Chinchen2, M. Millward8, N. Pavlakis9, M. Stockler2
  • 1Medical Oncology, Royal Perth Hospital, 6000 - Perth/AU
  • 2Nhmrc Clinical Trials Centre, University of Sydney, Sydney/AU
  • 3Clinical Trials Centre, Australasian Lung Cancer Trials Group, Sydney/AU
  • 4North Coast Cancer Institute, Coffs Harbour Health Campus, 2450 - Coffs Harbour/AU
  • 5Medical Oncology, The Prince Charles Hospital, Brisbane/AU
  • 6Medical Oncology, The Chris O'Brien Lifehouse, Sydney/AU
  • 7Medical Oncology, North Coast Cancer Institute, Port Macquarie/AU
  • 8Medical Oncology, Sir Charles Gardner Hospital, Perth/AU
  • 9Medical Oncology, Royal North Shore Hospital, Sydney/AU

Abstract

Aim

We sought to determine if the substantial benefits seen in a Japanese phase 2 trial of adding transdermal nitroglycerin to cisplatin and vinorelbine as first line chemotherapy for advanced non-small cell lung cancer (NSCLC) could be corroborated in a multicentre phase 3 trial with widely used platinum-based doublets.

Methods

Patients with advanced NSCLC were randomly allocated (1:1) to treatment with or without the daily application of a 25mg nitroglycerin patch for 2 days before, the day of, and 2 days after, each infusion of chemotherapy using standard, platinum-based doublet chemotherapy selected prior to randomisation. Minimisation was used to balance randomisation for gender, stage, histology, chemotherapy regimen, performance status, age and site. Progression free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), objective tumour response (OTR: complete response or partial response) and adverse events (AE). Accrual of 500 participants was designed to give 80% power to detect an improvement in median PFS from 6 months to 8 months (HR 0.75) with a 2-sided p-value of 0.05. Efficacy analyses were by intention to treat.

Results

Accrual was stopped after the first planned interim analysis based on 270 PFS events among 332 participants with a median follow-up of 18 months. This analysis showed that adding nitroglycerin had no demonstrable effect on PFS (median 5 months, hazard ratio 1.03, 95% CI 0.81 to 1.31, p = 0.79), OS (median 11 months, hazard ratio 1.03, 95% CI 0.79 to 1.36, p = 0.81), or OTRR (28%, RR 0.83, 95% CI 0.58 to 1.19, p = 0.31). AE seen more frequently with nitroglycerin included headache (53% v 28%, p < 0.001), dizziness (34% v 22%, p = 0.01), and diarrhoea (22% v 11%, p = 0.01). The most frequently used chemotherapy regimens were carboplatin and gemcitabine (78%), or carboplatin and paclitaxel (20%).

Conclusions

Nitroglycerin did not improve the outcomes of standard, first-line chemotherapy with a platinum-based doublet. Individually updated patient data from our trial, and from the Dutch NVALT-12 trial presented in June 2014 at ASCO, will be combined in a prospectively planned, individual patient data meta-analysis.

Disclosure

All authors have declared no conflicts of interest.