Whole brain radiotherapy with concurrent erlotinib for brain metastases from non-small cell lung cancer: A phase I study

Abstract

19122 Background: Whole brain radiotherapy (WBRT), the standard treatment for multiple brain metastases from NSCLC, results in a median survival of 4 months with approximately 50% of patients dying from intracranial progression. We performed a two-phase dose-escalation phase I trial (NCT00536861), evaluating the safety of WBRT with concurrent and maintenance erlotinib. Methods: Pts with untreated brain metastases from pathologically confirmed NSCLC were eligible. Erlotinib (cohort 1: 100mg/day; cohort 2: 150mg/day) was started 1 week prior to, and continued during, WBRT (30 Gy/10 fractions). Maintenance erlotinib (150mg/day) was continued until unacceptable toxicity or disease progression. Serial neuro-imaging was performed at 3-monthly intervals. The primary study end-point was toxicity. Secondary end-points were survival and time to disease progression. Results: 13 pts were enrolled between May 2006-Dec 2007. Two pts withdrew prior to WBRT due to rapid clinical progression and 11 pts (M:F 6:5, median age 65 years) completed WBRT. Median duration of erlotinib treatment was 78 days (range 38–523). No treatment-related toxicity ≥ grade 3 was observed in cohort 1 (4 pts). In cohort 2 (7 pts) grade ≥ 3 toxicity consisted of grade 3 acneiform rash (n=1); grade 3 fatigue (n=1); fatal interstitial lung disease (n=1). No treatment-related neurotoxicity was observed. Median overall survival was 130 days (range 42–557), with 3 pts alive at the time of analysis. Five pts developed an acneiform rash, including all 3 pts surviving > 150 days. Median time till disease progression was 96 days (range 38–523), which was located exclusively extracranially (n=6). No clinical intracranial progression was observed. In the 6 pts with follow-up neuro-imaging, the intracranial response was PR in 4 and SD in 2. Four pts without disease progression had died at the time of analysis: erlotinib- induced interstitial lung disease (n=1); COPD exacerbation (n=1); pulmonary embolism (n=1); congestive cardiac failure (n=1). Conclusions: WBRT (30 Gy/10 fractions) with concurrent erlotinib (150mg/day) is well tolerated in patients with brain metastases from NSCLC. The absence of clinical intracranial progression warrants further study of concurrent erlotinib and WBRT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche, the Netherlands