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27-08-2014 | Article

TKI added to whole-brain radiotherapy fails to raise NSCLC survival


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medwireNews: Concurrent use of the tyrosine kinase inhibitor (TKI) erlotinib and whole-brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases does not improve survival, research suggests.

For inclusion in the multicentre phase II trial, patients had to have histologically or cytologically confirmed NSCLC and be newly diagnosed with multiple brain metastases on magnetic resonance imaging or contrast computed tomography scanning.

However, patients did not need immediate chemotherapy for symptom control and also had to have a Karnofsky performance status of 70 or higher.

Treatment involved erlotinib (n=40) or matching placebo (n=40) taken once daily in conjunction with standard WBRT, administered as five daily fractions of 20 Gray. The dose of erlotinib was 100 mg/day during WBRT and increased to 150 mg/day at the completion of radiotherapy. The reason for the lower erlotinib dose during WBRT was because of concerns over possible neurotoxicity.

The primary endpoint of median neurological progression-free survival (nPFS) was 1.6 months after WBRT regardless of whether erlotinib was used or not, with a nonsignificant hazard ratio (HR) of 0.95 versus placebo.

Overall survival (OS), a key secondary endpoint, was also unaffected, with comparable median OS of 3.4 months for patients given erlotinib and 2.9 months for those given placebo in addition to WBRT, again with a nonsignificant HR of 0.95.

The median follow-up period was 12.6 months and 2-month nPFS was 38.9% and 38.5% in the erlotinib- and placebo-treated groups, respectively.

Rates of grade 3 or 4 adverse events were similar in the two patient groups, with the exception of known the known TKI side effect of rash (20.0 vs 5.0% for placebo) and higher rates of fatigue in the placebo versus the erlotinib-treated patients (35.0 vs 17.5%).

The results are somewhat disappointing considering erlotinib has been shown to have possible radiosensitising properties, write Siow Ming Lee, from University College London Hospitals in the UK, and co-investigators.

However, the team notes in the Journal of the National Cancer Institute that the study was conducted in an unselected patient population and the frequency of EGFR mutations was low, at just 3.9%.

“Our finding does not preclude the possibility that erlotinib is effective for EGFR mutation positive tumors,” they say, concluding that “future studies should focus on the role of erlotinib with or without WBRT in patients with EGFR mutations”.

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014

By Sara Freeman, medwireNews Reporter