Randomized trial of erlotinib plus whole-brain radiotherapy for NSCLC patients
with multiple brain metastases.
Author(s): Lee SM(1), Lewanski CR(2), Counsell N(2), Ottensmeier C(2), Bates A(2), Patel
N(2), Wadsworth C(2), Ngai Y(2), Hackshaw A(2), Faivre-Finn C(2).
Affiliation(s): Author information:
(1)Affiliations of authors: Department of Oncology, University College London (UCL)
Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology,
Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer
Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of
Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy
Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
sm.lee@uclh.nhs.uk.
(2)Affiliations of authors: Department of Oncology, University College London (UCL)
Cancer Institute and UCL Hospitals, London, UK (SML, NP); Department of Oncology,
Charing Cross Hospital, London, UK (CRL); Cancer Research UK and UCL Cancer
Trials Centre, UCL Cancer Institute, London, UK (NC, CW, YN, AH); Department of
Oncology, Southampton General Hospital, Southampton, UK (CO, AB); Radiotherapy
Related Research, The Christie NHS Foundation Trust, Manchester (CFF), UK.
Publication date & source: 2014, J Natl Cancer Inst. , 106(7). pii: dju151
BACKGROUND: Median survival of non-small cell lung cancer (NSCLC) patients with
brain metastases is poor. We examined concurrent erlotinib and whole brain
radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated
brain metastases, given the potential radiosensitizing properties of erlotinib
and its direct effect on brain metastases and systemic activity.
METHODS: Eighty NSCLC patients with KPS of 70 and greater and multiple brain
metastases were randomly assigned to placebo (n = 40) or erlotinib (100mg, n =
40) given concurrently with WBRT (20 Gy in 5 fractions). Following WBRT, patients
continued with placebo or erlotinib (150 mg) until disease progression. The
primary end point was neurological progression-free survival (nPFS); hazard
ratios (HRs) were calculated using Cox regression. All P values were two-sided.
RESULTS: Fifteen patients (37.5%) from each arm were alive and without
neurological progression 2 months after WBRT. Median nPFS was 1.6 months in both
arms; nPFS HR 0.95 (95% CI = 0.59 to 1.54; P = .84). Median overall survival (OS)
was 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI = 0.58
to 1.55; P = .83). The frequency of epidermal growth factor receptor (EGFR)
mutations was low with only 1 of 35 (2.9%) patients with available samples had
activating EGFR-mutations. Grade 3/4 adverse event rates were similar between the
two groups (70.0% in each arm), except for rash 20.0% (erlotinib) vs 5.0%
(placebo), and fatigue 17.5% vs 35.0%. No statistically significant quality of
life differences were found.
CONCLUSIONS: Our study showed no advantage in nPFS or OS for concurrent erlotinib
and WBRT followed by maintenance erlotinib in patients with predominantly EGFR
wild-type NSCLC and multiple brain metastases compared to placebo. Future studies
should focus on the role of erlotinib with or without WBRT in patients with EGFR
mutations.
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