Entry Detail
| General information | |
| Database: | DB00651 |
| Objective: | They evaluated the maximum tolerated dose (MTD) and feasibility of lapatinib given concurrently with whole brain radiotherapy (WBRT). Eligible patients had (human epidermal growth factor receptor 2)positive breast cancer and more than and equal to 1 brain metastasis. |
| Authors: | Lin NU, et al |
| Title: | a phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (human epidermal growth factor receptor 2)positive breast cancer brain metastases. |
| Journal: | Breast Cancer Res Treat |
| Year: | 2013 |
| PMID: | 24197661 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | brain metastases from human epidermal growth factor receptor 2-positive breast cancerhuman epidermal growth factor receptor 2positive breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 4 |
| Therapeutic Combination Content: | lapatinib with whole brain radiotherapy |
| Study Type: | phase I study |
| Key Patients Feature: | Patients with histologically confirmed, human epidermal growth factor receptor 2positivebreast cancer (3 staining by immunohistochemistry orgene amplification by fluorescence in situ hybridization)and new or progressive parenchymal CNS metastasis wereeligible. Measurable CNS disease was not required butpatients with leptomeningeal carcinomatosis only wereexcluded. Prior stereotactic radiosurgery (SRS) but notWBRT was allowed.Other key eligibility criteria included age C18, EasternCooperative Oncology Group (ECOG) performance status(PS) 0-2, life expectancy [12 weeks, adequate organfunction; left ventricular ejection fraction (LVEF) C50 %, and provision of informed consent. A 2 week washoutfrom prior treatments was required with exception oftrastuzumab. |
| Biomarker: | Human Epidermal Growth Factor Receptor 2 (human epidermal growth factor receptor 2)positive |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received lapatinib 750 mg twice on day one followed by 1000, 1250, or 1500 mg once daily. WBRT (37.5 Gy, 15fractions) began 18 days after starting lapatinib. Lapatinib was continued through WBRT. Following WBRT, patients received trastuzumab 2 mg/kg weekly and lapatinib 1000 mg once daily. |
| Primary End Point: | MDT, DLT and ORR |
| Secondary End Point: | NA |
| Patients Number: | 35 |
| Trial Results | |
| DLT_MTD: | During dose escalation, no patients receiving 1, 000 or 1, 250 mg and two of five patients receiving 1, 500 mg experienced DLTs (grade 3 mucositis and rash). Overall, 7/27 patients at 1, 250 mg (MTD) had DLTs: grade 3 rash (n = 2), diarrhea (n = 2), hypoxia (n = 1), and grade 4 pulmonary embolus (n = 2). |
| Objective Response Rate: | Among 28 evaluable patients, the CNS objective response rate (ORR) was 79 % [95% confidence interval (CI) 5992 %] by prespecified volumetric criteria; 46 % remained progression free (CNS or nonCNS) at 6 months. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.8 months (range 0-58.3 months) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The majority were grade 1-2. The most common grade 3 toxicities included diarrhea (n = 6) and acneiform rash (n = 3). Grade 4 toxicities included pulmonary embolus (PE) (n = 2) and fatigue (n = 1). |
| Conclusions: | The study did not meet the predefined criteria for feasibility because of toxicity, although the relationship bettheyen study treatment and some DLTs was uncertain. Given the high ORR, concurrent lapatinibWBRT could still be considered for future study with careful safety monitoring. |