Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.
Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life.



The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061.



Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to receive either OSC plus WBRT (269) or OSC alone (269). Baseline characteristics were balanced between groups, and the median age of participants was 66 years (range 38-85). Significantly more episodes of drowsiness, hair loss, nausea, and dry or itchy scalp were reported while patients were receiving WBRT, although there was no evidence of a difference in the rate of serious adverse events between the two groups. There was no evidence of a difference in overall survival (hazard ratio 1·06, 95% CI 0·90-1·26), overall quality of life, or dexamethasone use between the two groups. The difference between the mean QALYs was 4·7 days (46·4 QALY days for the OSC plus WBRT group vs 41·7 QALY days for the OSC group), with two-sided 90% CI of -12·7 to 3·3.



Although the primary outcome measure result includes the prespecified non-inferiority margin, the combination of the small difference in QALYs and the absence of a difference in survival and quality of life between the two groups suggests that WBRT provides little additional clinically significant benefit for this patient group.



Cancer Research UK, Medical Research Council Clinical Trials Unit at University College London, and the National Health and Medical Research Council in Australia.
Northern Centre for Cancer Care, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Paula
P
Mulvenna
Medical Research Council Clinical Trials Unit at University College London, London, UK.
Matthew
M
Nankivell
Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Hull, UK.
Rachael
R
Barton
Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK.
Corinne
C
Faivre-Finn
Bristol Haematology and Oncology Centre, Bristol, UK.
Paula
P
Wilson
Newcastle Clinical Trials Unit and Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
Elaine
E
McColl
Wales Cancer Research Network, Cardiff UK.
Barbara
B
Moore
The Beatson West of Scotland Cancer Centre, Greater Glasgow Health Board and Clyde, Glasgow, UK.
Iona
I
Brisbane
Patient representative, Manchester, UK.
David
D
Ardron
Trans Tasman Radiation Oncology Group, Waratah, NSW, Australia; University of Queensland, QLD, Australia.
Tanya
T
Holt
Nottingham University Hospital, Nottingham, UK.
Sally
S
Morgan
Weston Park Hospital, Sheffield, UK.
Caroline
C
Lee
Queen Elizabeth Hospital, Kings Lynn, UK.
Kathryn
K
Waite
Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK.
Neil
N
Bayman
Medical Research Council Clinical Trials Unit at University College London, London, UK.
Cheryl
C
Pugh
Medical Research Council Clinical Trials Unit at University College London, London, UK.
Benjamin
B
Sydes
Medical Research Council Clinical Trials Unit at University College London, London, UK.
Richard
R
Stephens
Medical Research Council Clinical Trials Unit at University College London, London, UK.
Mahesh K
MK
Parmar
Medical Research Council Clinical Trials Unit at University College London, London, UK. Electronic address: ruth.langley@ucl.ac.uk.
Ruth E
RE
Langley
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000556:secondary* / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy / Q000556:secondary* / Q000628:therapy*; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008875:Middle Aged; D010166:Palliative Care; D011788:Quality of Life; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D003907:Dexamethasone