No Survival Benefits With Erlotinib and Whole-Brain Radiotherapy for NSCLC With Multiple Brain Metastases


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“To exploit the potential radiosensitizing properties, the direct effect on brain metastases, and systemic activity of erlotinib,” researchers from the United Kingdom tested concurrent erlotinib and whole-brain radiotherapy followed by maintenance erlotinib in patients with of non–small cell lung cancer (NSCLC) and untreated brain metastases. No significant improvements in neurologic progression-free survival (the primary endpoint of the study), overall survival, or quality of life were found for patients receiving whole-brain radiotherapy with erlotinib vs placebo, Siow Ming Lee, MD, PhD, of University College London (UCL) and UCL Hospitals, and colleagues reported in the Journal of the National Cancer Institute.

The 80 study patients all had Karnfosky performance status of 70 and multiple brain metastases. Inclusion criteria also included Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) class I and II. Class I is defined as Karnofsky score ≥ 70, controlled primary tumor, and metastases to brain only, whereas class II involves uncontrolled primary tumor or primary controlled but metastases to brain and other sites, the investigators explained.

“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,” the researchers noted. The median age was 62.2 years in the placebo group and 61.3 years in the erlotinib group.

Patients were randomly assigned in equal numbers to receive placebo or erlotinib at 100 mg/d given concurrently with whole-brain radiotherapy at 20 Gy in 5 fractions. Patients continued with placebo or erlotinib at 150 mg/d until disease progression.

At 2 months after whole-brain radiotherapy, 15 patients (37.5%) from each arm were alive and without neurologic progression. Median neurologic progression-free survival was 1.6 months in both arms (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.59–1.54, P = .84). Median overall survival was 2.9 in the placebo arm and 3.4 months in the erlotinib arm (HR = 0.95, 95% CI = 0.58 to 1.55, P = .83).

“The median neurological [progression-free survival] and [overall survival] in this group were disappointingly low; 1.6 months and 3.4 months respectively, despite selecting only patients with age-modified RTOG RPA class I and II,” the researchers wrote.

Overall 70% of patients in both groups experienced a grade 3/4 adverse event. Rash was more frequent in the erlotinib group (20% vs 5% in the placebo group), and fatigue was more frequent in the placebo group (35% vs 17.5% for the erlotinib group). No statistically significant quality-of-life differences were observed.

“Our finding does not preclude the possibility that erlotinib is effective for EGFR mutation positive tumors as only 2.9% of assessed patients manifested EGFR mutations,” the investigators wrote. “Future studies should focus on the role of erlotinib with or without [whole-brain radiotherapy] in NSCLC patients harboring EGFR mutations.” ■

Lee SM, et al: J Natl Cancer Inst 106(7):dju151, 2014.



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