Entry Detail
| General information | |
| Database: | DB00449 |
| Objective: | Human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2) amplification is present in a subgroup of gastrooesophageal cancers (GCs). human epidermal growth factor receptor 2 inhibition with trastuzumab has shown to improve outcomes in advanced disease. Lapatinib ditosylate (LAP), a dual antiepidermal growth factor receptor (EGFR) and antihuman epidermal growth factor receptor 2 tyrosine kinase inhibitor with preclinical activity against GC, has been approved in human epidermal growth factor receptor 2positive breast cancer. they aimed to study the activity of LAP in human epidermal growth factor receptor 2amplified GC. |
| Authors: | Lorenzen S, et al |
| Title: | Lapatinib versus lapatinib plus capecitabine as secondline treatment in human epidermal growth factor receptor 2amplified metastatic gastrooesophageal cancer: a randomisedphase II trial of the Arbeitsgemeinschaft Internistische Onkologie. |
| Journal: | Eur J Cancer. |
| Year: | 2015 |
| PMID: | 25694417 |
| Trial Design | |
| Clinical Trial Id: | NCT01145404 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | human epidermal growth factor receptor 2positive advanced gastroesophageal junction cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | lapatinib plus capecitabine |
| Study Type: | a randomisedphase II trial |
| Key Patients Feature: | Patients P18 years with histologically confirmedhuman epidermal growth factor receptor 2positive metastatic gastrooesophageal adenocarcinoma (GC) were eligible for inclusion if they had documented disease progression during or within 6 monthsafter treatment with at least one cytotoxic regimen formetastatic disease including a platinum compound.The human epidermal growth factor receptor 2 status was considered positive when human epidermal growth factor receptor 2gene amplification (human epidermal growth factor receptor 2/CEP17 ratio P2.0) was confirmed by central lab using fluorescent in situ hybridisation (FISH) (human epidermal growth factor receptor 2 FISH pharmDxe Kit (Dako). Thehuman epidermal growth factor receptor 2/CEP17 ratio was deemed preferable to the heterogeneous human epidermal growth factor receptor 2 immunohistochemistry (IHC) stainingpattern and the subjective categorisation according todifferent IHC scores used in routine practice. Furtherinclusion criteria were an Eastern Cooperative OncologyGroup performance status 62; a left ventricular ejectionfraction (LVEF) of P50%, a measurable cancer lesion, life expectancy of at least 12 weeks and an adequate haematological, renal and hepatic function. |
| Biomarker: | human epidermal growth factor receptor 2amplified |
| Biomark Analysis: | NA |
| Control Group Info: | A:Lapatinib B: lapatinib plus capecitabine |
| Treatment Info: | patients were randomly allocated 1:1 to receive LAP 1250mg per day 121 plus capecitabine (CAP) 2000mg/m(2) on days 114 of a 21day cycle or LAP 1500mg monotherapy day 121 after having failed on a platinumbased firstline therapy. human epidermal growth factor receptor 2 status was assessed centrally. |
| Primary End Point: | the objective response rate (ORR) |
| Secondary End Point: | NA |
| Patients Number: | 37 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Only two pts (11.1%; 95% confidence interval (CI): 1.3734.7), both in the LAP+CAP arm, achieved an objective response |
| Disease Control Rate: | 17% for LAP + CAP and 11% for LAP |
| Median Time to Progression: | 42 (95% CI: 38-61) days in the LAP group and 83 (95% CI: 42-86) days in the LAP + CAP group. |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | Median OS was not reached in the combinationtherapy group and was 142 days with LAP monotherapy (HR 1.06; 95% CI 0.34-3.29) |
| Adverse Event(agent arm): | All patients in the LAP + CAP group had adverse events of any grade compared with 17 (89.5%) patients in the LAP group. Most AEs were grade 1 or 2. Diarrhoea, fatigue and nausea were the most common adverse events in both treatment arms, however diarrhoea was more common in the combination than in the monotherapy group (61 versus 26%) but was generally mild. Severe adverse events (CTCAE grade 3-5) were comparable in both arms (10 patients in each group). Cardiac events were identified in three patients (17%) in the combinationtherapy group (n = 2 sinus tachycardia, n = 1 palpitations) and in two patients (11%) in the monotherapy group (n = 2 tachyarrhythmia). All of these events were considered to be unrelated to treatment, and all patients had a left ventricular ejection fraction (LVEF) value that was at or above the lotheyr limit of the normal range on subsequent assessment. |
| Conclusions: | Lapatinib showed insufficient activity in human epidermal growth factor receptor 2amplified pretreated advanced GC. The safety profile of LAP or LAP+CAP was as expected with some more toxicity in the combination arm. (ClinicalTrials.gov Identifier,?NCT01145404). |