| General information |
| Database: | DB00403 |
| Objective: | yrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have activity in solid tumors. The authors evaluated an oral EGFR TKI, erlotinib, in patients with previously treated esophageal cancer. |
| Authors: | Ilson DH, et al |
| Title: | a phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus. |
| Journal: | Cancer. |
| Year: | 2011 |
| PMID: | 21425140 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | single center, single armphase II study |
| Key Patients Feature: | Patients had a histologic diagnosis of metastatic or surgically unresectable adenocarcinomaor squamous cell carcinoma of the esophagus or gastroesophageal junction, confirmed atMemorial Hospital. Tumors extending into the stomach had to have at least 50%involvement of the distal esophagus (Sietheyrt types I and II). Prior radiotherapy waspermitted. Up to one prior chemotherapy regimen for the treatment of metastatic disease, and up to two if one was administered as adjuvant or neoadjuvant treatment, were allowed.Measurable disease was required, defined as at least one lesion measurable in onedimension, either more than and equal to 20 mm with conventional techniques, or more than and equal to 10 mm with spiral CT scan.Eligibility also included a Karnofsky performance status more than and equal to 70%, and organ function definedby an absolute neutrophil count more than and equal to 1, 500/¦ÌL, platelet count more than and equal to 100, 000/¦ÌL, bilirubin less than2 times the upper limit of normal, AST less than 2 times the upper limits of normal, serumcalcium less than and equal to 12 mg/dl, and creatinine less than and equal to 1.5 mg/dl. All patients¡¯ tumor tissue was tested for EGFR expression prior to initiating therapy |
| Biomarker: | EGFR expression |
| Biomark Analysis: | No mutations in exons 18, 19 and 21 of the EGFR were observed in the 5 patient tumorsamples tested, including one patient with squamous cell carcinoma with a partial response. |
| Control Group Info: | single arm |
| Treatment Info: | pts received 150 mg erlotinib daily. EGFRnegative tumors (6 patients; 20%) and EGFRover expressing tumors (24 patients; 80%) were treated. |
| Primary End Point: | antitumor response rate. |
| Secondary End Point: | the response rate by tumor histology, toxicity, time to progression, and overall survival. |
| Patients Number: | 30 |
| Trial Results |
| DLT_MTD: | Most toxicities were grade 1 or 2, with the exception of dermatologic toxicity or skin rash(grade 3 in 10% of patients, grade 1-2 in 67%) |
| Objective Response Rate: | Two partial responses were seen in the EGFR+ cohort (2/24, 8%), and no responses inthe EGFR cohort (0/6). Reponses were limited to squamous cell cancer (2/13, 15%, duration 5.5-7 months) |
| Disease Control Rate: | NA |
| Median Time to Progression: | Time to tumor progression was greater in squamous cell (3.3 months, range 1-24 months) compared to adenocarcinoma (1.6 months, range 1-6 months, p = 0.026). |
| Median PFS A vs. C: | in squamous cancer (median 5 months, range 2-24 months) was longer compared to adenocarcinoma (median 3.5 months, range 2-6 months). |
| Median OS A vs. C: | The median survival in all patients was 10.3 months, 8.2 months for squamous cell cancer and 11.2 months for adenocarcinoma (p = 0.75). |
| Adverse Event(agent arm): | Most toxicities were grade 1 or 2, with the exception of dermatologic toxicity or skin rash (grade 3 in 10% of patients, grade 1-2 in 67%). Diarrhea was at worst grade 2 in 13%. Six patients (20%) required a dose reduction to 100 mg daily, five for skin rash and one for diarrhea. No patients were taken off therapy due to drug toxicity, only to progressive disease. |
| Conclusions: | Erlotinib had limited activity in patients with esophageal cancer, and responses and some protracted stable disease were observed in those with squamous cell carcinoma. Efficacy according to EGFR status could not be assessed given the rarity of EGFRnegative tumors. The current results indicated that further evaluation of this agent in squamous cell carcinoma is warranted.? |