You are here
Treatment strategies for metastatic esophageal cancer
Prof. Antione Adenis
Treatment strategies for metastatic esophageal cancer
Professor Antoine Adenis
Head, Gastrointestinal Oncology Department, Centre Oscar Lambret, Lille, France
I am the main investigator of the E-DIS trial, a randomised phase 2 trial, which is a discontinued trial of first-line chemotherapy in the field of metastatic squamous oesophageal cell cancer.
As you may know oesophageal cancer includes two histological types, the adenocarcinoma type, which is frequent in the western world and the squamous cell oesophageal cancer, which is frequent in Asia and globally over the world.
We focused our intentions on the metastatic squamous oesophageal cancer, because conversely as it is known in the adenocarcinoma type where metastatic cancers have improved overall survival and improved quality of life with chemotherapy, such evidence is not present for the metastatic squamous oesophageal cancer.
As most of the physicians are intimately convinced that chemotherapy improves survival in the setting of metastatic squamous cell oesophageal cancer, it is not possible to set up a randomised trial versus best supportive care in that setting. This attitude leads to the delivery of cytotoxics with unproven benefit but some side effects, and unjustified costs.
Consequently, we launched the E-DIS trial, a study dedicated to patients with metastatic squamous cell oesophageal cancer in the first-line setting. All the patients received a 5FU/platinum based regimen and, after early tumour assessment done at week 6, patients were randomised between two arms of treatment, a best supported care arm with chemo discontinuation and a chemo continuation arm plus best supportive care.
The main objective of that study was to estimate the nine month survival rate. 31 patients per arm of treatment were needed. The control arm served as an internal control, without formal comparison intent.
Secondary objectives included overall survival, progression free survival, quality of life as well as medical costs. 105 patients were selected and treated with a 5FU platinum based regimen, actually mostly a FOLFOX regimen in three patients out of four. Among these 105 patients, 90 patients were available for tumour assessment. At first tumour assessment, 90 patients were found evaluable, 23 patients left the study, most of the time because of tumour progression or for ECOG PS worsening. Finally, 67 patients were randomised between the two arms of treatment and these patients were included in the intend-to-treat analysis.
Back to the results, nine month survival rate was 50% in the chemo continuation arm and 48% in the chemo discontinuation arm. When we looked at the overall survival curves we found that the median overall survival of patients included in the chemo continuation arm was 8.5 months and the median survival of patients included in the chemo discontinuation arm was 8.8 months.
As most of the patients included in the chemo discontinuation arm got some chemotherapy at the time of progression we looked at the overall survival curve of these patients, whether or not they got post progression chemotherapy. We found that patients who had no post progression chemotherapy in the chemo discontinuation arm had a median survival of 3.5 months, whereas patients included in the chemo discontinuation arm who got some chemotherapy after progression had a median survival of 9.9 months.
Regarding PFS curves, we found that PFS was about 1.8 months in the chemo discontinuation arm and about four months in the chemo continuation arm. Interestingly, looking at the quality of life data, assessed every six weeks with the EORTC QLQ-C30 questionnaire, we found that the time until definitive deterioration of global health status looked much better in the chemo continuation arm with a median time until definitive deterioration of 6.8 months versus 4.5 months in the chemo discontinuation arm.
Because survival looked similar in both arms of treatment, we concluded at the last ASCO meeting, that both strategies could be adequate standard treatments for further randomized trial in that setting.
Furthermore, we noticed that PFS as well as time to definitive deterioration of global health status, looked much better in the chemo continuation arm.
In this World GI Congress we present additional data regarding quality of life, with the OES18 quality of life questionnaire focusing on key domains of this quality of life questionnaire dedicated to oesophageal cancer, we found that time until definitive deterioration of the eating domain, the dysphagia domain, and the oesophageal pain domain, appeared longer in the chemo continuation arm than in the chemo discontinuation arm.
To conclude, is the E-DIS trial is the 1st randomized trial which included a best supportive care arm – actually a chemo discontinuation arm plus best supportive care arm - in the setting of MSEC. We found that most of the patients in the chemo discontinuation arm got some chemotherapy as post-progression treatment and we found that this treatment given post-progression provided a survival benefit.
Finally, although overall survival did not look much different with either strategies, progression free survival and quality of life, including key domains of the EORTC quality of life questionnaire dedicated to esophageal cancer, looked much better with chemotherapy continuation. With these results, we are enough confident to conclude that chemotherapy is standard of care for most of the patients with metastatic squamous cell esophageal cancer, mainly those in good performance status.