medwireNews: The epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) icotinib significantly delays intracranial disease progression compared with whole-brain irradiation (WBI) plus chemotherapy in patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, Chinese researchers report.
The findings indicate that “icotinib should be considered as a new first-line therapeutic option in this patient population,” they say.
The phase III, multicenter, open-label BRAIN trial included 158 patients with EGFR-mutant NSCLC, who were naive to treatment with EGFR-TKIs or radiotherapy and had at least three metastatic brain lesions. The patients were randomly assigned to receive oral icotinib 125 mg three times per day (n=85) or WBI (30 Gy in 10 fractions of 3 Gy; n=73) plus concurrent or sequential chemotherapy for 4–6 cycles, until unacceptable adverse events or intracranial disease progression occurred.
During a median 16.5 months of follow-up, 46 patients in the icotinib group and 34 in the WBI group experienced intracranial progression or death, with median intracranial progression-free survival (PFS) at 10.0 and 4.8 months, respectively. This was equivalent to a significant 44% reduction in the risk for these outcomes with icotinib versus WBI.
Median PFS was also significantly longer with icotinib than with WBI, at 6.8 versus 3.4 months, but there was no difference in overall survival between the two groups (18.0 and 20.5 months, respectively).
The researchers say that this lack of difference is likely due to the higher number of patients who switched from WBI to icotinib at initial disease progression (89%) compared with those switching from icotinib to WBI (76%).
Yi-Long Wu (Guangdong Academy of Medical Sciences, China) and colleagues also report that significantly more patients receiving icotinib, compared with WBI, had intracranial (65 vs 37%), extracranial (52 vs 10%), and overall (67 vs 19%) objective responses.
In terms of safety, grade 3 or worse adverse events were less common in the icotinib group than in the WBI group (8 vs 38%). Elevated alanine aminotransferase concentrations and rash were the most commonly reported adverse events of any grade, occurring in around 20% and 30% of each group, respectively.
Writing in The Lancet Respiratory Medicine, Wu et al point out that, at the time of the trial icotinib was only approved for use in China, “therefore the results in this trial cannot be validated soon.”
They add: “In future studies, investigation of the use of EGFR-TKIs in combination with WBI and optimal sequences between EGFR-TKIs and WBI are warranted.”
In an accompanying comment, Rafael Rosell (Germans Trias i Pujol Health Sciences Institute and Hospital, Barcelona, Spain) and Niki Karachaliou (University Hospital Sagrat Cor, Barcelona, Spain) caution that although the findings “clearly showed that icotinib significantly increased intracranial progression-free survival compared with WBI,” a separate pooled analysis of trials among similar patients showed that “the use of an EGFR TKI and deferred radiotherapy is associated with shorter overall survival compared with radiotherapy followed by EGFR TKI.”
They conclude: “EGFR TKIs are warranted in the treatment of EGFR-mutant NSCLC with brain metastases; however, we highly recommend the initial ablation of brain metastases by stereotactic radiosurgery to optimise patient outcome.”
By Laura Cowen
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