Can WBRT be omitted in NSCLC patients with brain metastases not suitable for stereotactic radiosurgery or surgical resection? Results from the UK Medical Research Council QUARTZ randomised clinical trial.

Paula Mulvenna1,Matthew Nankivell2,Rachael Barton3,Corinne Faivre-Finn4,Paula Wilson5,Barbara Moore6,Elaine McColl7,Iona Brisbane8,Dave Ardron2,Benjamin Sydes2,Cheryl Pugh2,Tanya Holt9,Neil Bayman4,Sally Morgan10,Caroline Lee11,Kathryn Waite12,Richard Stephens2,Max Parmar2,Ruth Langley2

1Northern Centre for Cancer Care, Newcastle upon Tyne, UK,2MRC Clinical Trials Unit at UCL, London, UK,3Castle Hill Hospital, East Yorkshire, UK,4The Christie, Manchester, UK,5Bristol Haematology & Oncology Centre, Bristol, UK,6University Hospital Llandough, South Glamorgan, UK,7Royal Victoria Infirmary, Newcastle upon Tyne, UK,8Beatson West of Scotland Cancer Centre, Glasgow, UK,9Mater Hospital, Brisbane, Queensland, Australia,10Nottingham University Hospitals, Nottingham, UK,11Weston Park Hospital, Sheffield, UK,12Queen Elizabeth Hospital, King’s Lynn, UK

Presenting date: Wednesday 4 November

Background

 

 

Brain metastases affect up to 40% of patients with non-small cell lung cancer (NSCLC), and for inoperable cases, whole brain radiotherapy (WBRT) and dexamethasone is standard treatment. However there are no randomised clinical trials to show whether WBRT improves either quality of life or survival.

 

Method

 

 

A phase III randomised non-inferiority trial with a primary outcome measure of quality adjusted life years (QALYs). Patients with inoperable brain metastases from NSCLC, were randomly allocated to either optimal supportive care (OSC), including dexamethasone, plus WBRT 20 Gy/5f (OSC+WBRT) or OSC alone. The trial sought to exclude more than a one week detriment in QALYs in the OSC alone arm.

 

Results

 

 

From 2007-2014, 538 patients were recruited from 69 UK and 3 Australian centres. Baseline characteristics were well balanced: 58% male; median age 66 years (range 38 – 85); 38% Karnofsky performance status (KPS) <70; 54% extracranial metastases; 30% solitary brain metastasis.

 

Median survival was 66 days (OSC+WBRT) vs 57 days (OSC), hazard ratio 1.10 (95% CI 0.93 - 1.30). The mean QALY was 45.4 days (OSC+WBRT) vs 41.2 days (OSC), difference -4.2 days (90% CI -13.5 - +4.7).

 

In subgroup analyses, younger age, higher KPS, metastases confined to the brain, controlled primary tumour, and lower recursive partitioning analysis (RPA) or graded prognostic assessment (GPA) class were all prognostic of improved QALYs and overall survival.

 

Younger patients (<60) appeared to derive more benefit from WBRT in terms of both QALYs and overall survival than older patients (?70).

 

Conclusion

 

 

This is the only large randomised trial evaluating WBRT in NSCLC.  Although the results include the pre-specified non-inferiority margin of one week, the estimate of the difference in QALYs is small, questioning the widespread use of WBRT. RPA and GPA class, whilst prognostic of improved QALYs and survival, were not predictive of benefit from WBRT.