| General information |
| Database: | DB00645 |
| Objective: | Brain metastasis (BM) is a leading cause of death from non small cell lung cancer (non small cell lung cancer). Reasoning that activation of the epidermal growth factor receptor (EGFR) contributes to radiation resistance, they undertook a phase II trial of the EGFR inhibitor erlotinib with wholebrain radiation therapy (WBRT) in an attempt to extend survival time for patients with BM from non small cell lung cancer. Additional end points were radiologic response and safety. |
| Authors: | theylsh JW, et al |
| Title: | Phase II trial of erlotinib plus concurrent wholebrain radiation therapy for patients with brain metastases from non small cell lung cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23341526 |
| Trial Design |
| Clinical Trial Id: | NCT00871923 |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | brain metastases from non-smallcell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 4 |
| Therapeutic Combination Content: | erlotinib plus concurrent wholebrain radiation therapy |
| Study Type: | prospectivephase II study |
| Key Patients Feature: | Eligibility criteria included newly radiographically diagnosed brain metastasis from non small cell lung cancer, with or without prior craniotomy or stereotactic radiosurgery; age 18 years or older; Karnofsky performance score (KPS) 70; andevidence of normal hematologic and hepatic function during the 30 daysbefore starting the protocol treatment |
| Biomarker: | EGFR mutation status |
| Biomark Analysis: | Of 17 patients with known EGFR status, median survival time was 9.3 months for those with wildtype EGFR and 19.1 months for those with EGFR mutations. |
| Control Group Info: | single arm |
| Treatment Info: | Erlotinib was given at 150 mg orally once per day for 1 week, then concurrently with WBRT (2.5 Gy per day 5 days per week, to 35 Gy), followed by maintenance. EGFR mutation status was tested by DNA sequencing at an accredited core facility. |
| Primary End Point: | improvement in median survival compared with that of historical controls |
| Secondary End Point: | radiologic response and safety |
| Patients Number: | 40 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The overall response rate was 86% (n = 36). |
| Disease Control Rate: | 0.9 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.2 months |
| Median OS A vs. C: | 11.8 months (95% CI, 7.4 to 19.1 months). 9.3 months for those with wildtype EGFR and 19.1 months for those with EGFR mutations. |
| Adverse Event(agent arm): | No increase in neurotoxicity was detected, and no patient experienced grade 4 toxicity, but three patients required dose reduction for grade 3 rash. |
| Conclusions: | Erlotinib was well tolerated in combination with WBRT, with a favorable objective response rate. The higherthanexpected rate of EGFR mutations in these unselected patients raises the possibility that EGFRmutated tumors are prone to brain dissemination. |