| General information |
| Database: | DB00642 |
| Objective: | They 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. |
| Authors: | Lee SM, et al |
| Title: | Randomized trial of erlotinib plus wholebrain radiotherapy for non small cell lung cancer patients with multiple brain metastases. |
| Journal: | J Natl Cancer Inst. |
| Year: | 2014 |
| PMID: | 25031274 |
| Trial Design |
| Clinical Trial Id: | NCT00554775 |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | brain metastases from non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 4 |
| Therapeutic Combination Content: | erlotinib plus wholebrain radiotherapy |
| Study Type: | a twostage randomized, multicenter, phase II doubleblind, placebo controlled trial |
| Key Patients Feature: | histologically or cytologically confirmednon small cell lung cancer and newly diagnosed multiple BM documented by MRI orcontrast CT scan, but did not require immediate chemotherapy forsymptom control; aged 18-76 years; no previous cranial radiotherapy; at least 28 days since any chemotherapy; Glasgow Coma Scoreof 14 and greater; Karnofsky performance status of 70 and greater;3 or fetheyr sites of extracranial metastases; adequate renal and liverfunction; negative pregnancy test; and agemodified (age cutoff76 years instead of 66 years) Radiation Therapy Oncology GroupRecursive Partitioning Analysis (RTOG RPA) class I and II (class I isKPS more than and equal to 70, controlled primary tumor, metastases to brain only, andclass II is uncontrolled primary tumor, or primary controlled, but metastases to brain and other sites) |
| Biomarker: | epidermal growth factor receptor (EGFR) mutations |
| Biomark Analysis: | The frequency of epidermal growth factor receptor (EGFR) mutations was low with only 1 of 35 (2.9%) patients with available samples had activating EGFRmutations. |
| Control Group Info: | single arm |
| Treatment Info: | patients 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. |
| Primary End Point: | neurological progression free survival (nPFS) |
| Secondary End Point: | NA |
| Patients Number: | 15 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.6 months in both arms; nPFS HR 0.95 (95% CI = 0.59 to1.54; P = .84). |
| Median OS A vs. C: | 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI = 0.58 to 1.55; P = .83). |
| Adverse Event(agent arm): | 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 wildtype non small cell lung cancer 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. |