| General information |
| Database: | DB00435 |
| Objective: | Evidence is scarce for the effectiveness of therapies for oesophageal cancer progressing after chemotherapy, and no randomised trials have been reported. They aimed to compare gefitinib with placebo in previously treated advanced oesophageal cancer. |
| Authors: | Dutton SJ, et al |
| Title: | Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, doubleblind, placebocontrolled randomised trial. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 24950987 |
| Trial Design |
| Clinical Trial Id: | ISRCTN29580179 |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma, squamouscell carcinoma, or poorly differentiated oesophageal cancer or type I/II Siewert junctionaltumours, |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase III, multicentre, doubleblind, placebocontrolled randomised trial |
| Key Patients Feature: | Eligible patients were adults(more than and equal to 18 years) with histologically confirmed adenocarcinoma, squamouscell carcinoma, or poorly differentiatedoesophageal cancer or type I/II Sietheyrt junctionaltumours, had up to two previous chemotherapy and onechemoradiotherapy regimens, WHO performancestatus 0-2, ability to swallow tablets, no contraindicationsto gefi tinib, and either measurable or evaluable diseaseon CT. Patients with brain metastases were deemedeligible if were stable after cranial irradiation atstudy entry |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A: gefitinib B: placebo |
| Treatment Info: | Participants were recruited from 48 UK centres and randomly assigned (1:1) to gefitinib (500 mg) or matching placebo by simple randomisation with no stratification factors. Patients, clinicians, and trial office staff were masked to treatment allocation. Treatment continued until disease progression, unacceptable toxicity, or patient choice. |
| Primary End Point: | overall survival |
| Secondary End Point: | NA |
| Patients Number: | 450 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 54 (24%) of 224 patients in the gefitinib group had disease control at 8 weeks (48 stable disease and six partial response) as did 35 (16%) of 225 patients in the placebo group (34 stable disease and one partial response) (p=0.023). 40 (23%) of 170 patients with adenocarcinoma treated with gefitinib had disease control at 8 weeks as did 14 (28%) of 50 patients with squamouscell carcinoma treated with gefitinib (p=0.478). When observed, objective responses were rapid: seven responses were seen at week 4 and only one additional response was first recorded at week 8. These responses were durable with a range of 1.17-7.33 months. Only 98 (22%) of 449 patients had further therapy once they came off study treatment, with no differences in patients receiving further therapy between the two groups. 44 (10%) of 449 patients received further chemotherapy (23 [10%] of 225 on placebo and 21 [9%] of 224 on gefitinib); 43 (10%) of 449 patients were treated with palliative radiotherapy (24 [11%] of 225 on placebo and 19 [8%] of 224 on gefitinib); 30 (7%) of 449 patients were treated with stents (17 [8%] of 225 on placebo and 13 [6%] of 224 on gefitinib) and 13 (3%) of 449 with other treatments. |
| Disease Control Rate: | 24% of patients in the gefitinib group; 16% of patients on placebo. (p=0.023) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.57 months, 95% CI 1.23-1.90 in the gefitinib group vs 1.17 months, 95% CI 1.07-1.37 in the placebo group; HR 0.80, 95% CI 0.66-0.96, p=0.020 |
| Median OS A vs. C: | 3.73 months, 95% CI 3.23-4.50, for gefitinib vs 3.67 months, 95% CI 2.97-4.37, for placebo; hazard ratio [HR] 0.90, 95% CI 0.74-1.09, p=0.29 |
| Adverse Event(agent arm): | The most common toxicities were diarrhoea (36 [16%] of 224 patients on gefitinib vs six [3%] of 225 on placebo) and skin toxicity (46 [21%] vs two [1%]), both mostly grade 2. The commonest grade 3-4 toxicities were fatigue (24 [11%] vs 13 [6%] patients) and diarrhoea (13 [6%] vs two [1%]). Serious adverse events were reported in 109 (49%) of 224 patients assigned to gefitinib and 101 (45%) of 225 on placebo. |
| Conclusions: | The use of gefitinib as a secondline treatment in oesophageal cancer in unselected patients does not improve overall survival, but has palliative benefits in a subgroup of these difficult-to-treat patients with short life expectancy. Future research should focus on identification of predictive biomarkers to identify this subgroup of benefiting patients. |