As you know, oesophageal cancer is a high burden globally but for oesophageal squamous cell carcinoma, especially for [??] mostly East Asian parties, especially in China, because we know that more than 50% of the patients occur with oesophageal cancer in China. So we wanted to do some research for the resectable patients with oesophageal cancer, ESCC, which kind of a modality of neoadjuvant treatment could be better for the patients.
As we all know, chemoradiotherapy is the golden standard right now for the resectable ESCC patients, also for neoadjuvant chemotherapy. But we do not know if adding the ICI or immunotherapy is better or not. So that is the SCIENCE clinical trial we wanted to do. Three arms are comparable for the different treatment modalities for the ESCC patients.
Could you outline the methodology?
I think this is the first phase III clinical trial randomised for ESCC which compared three arms. Arm A is the chemotherapy combined with immunotherapy, sintilimab, group B is chemoradiotherapy combined with immunotherapy and compared to group C, the chemoradiotherapy as the golden standard treatment as a control group. That’s the methodology. After the neoadjuvant treatment we would do surgery and most of the patients [recommended] minimally invasive surgery for those patients. We also combined the ctDNA analysis for this whole clinical trial.
What did you find?
It’s very interesting, there were two principle key findings for this research, because this is the second interim analysis for this research we reported it this time at the ASCO meeting. The first is the pCR results because we have two primary endpoints, one is the pCR, one is EFS; the EFS we need to wait for the follow-up. The pCR rate is showing the chemoradiotherapy combined with immunotherapy has a very high pCR rate that’s nearly 58%. In Group A for chemo combined with immunotherapy around 18-20% pCR rate and in the chemoradiotherapy group it’s stable at about 49% pCR rate compared to the cross-trial. So this is the first finding, that is the chemoradiotherapy combined with immunotherapy can bring a higher pCR rate for ESCC patients.
The second key point for this finding is the ctDNA. We used 92 patients for ctDNA this time and in the baseline we can see nearly 97-98% who had positive ctDNA for locally advanced ESCC. After the treatment cycle and before surgery we can see the trend is very dramatically decreasing for the ctDNA positive, based on the treatment, no matter for group A, B or C. But it’s very interesting that in the pCR group and the [mPR] group most of the patients in the pCR group, nearly 85%, it is ctDNA negative. So this is very impressive and shows that the treatment modality combined with ctDNA can predict those patients in the near future.
What impact could these findings have?
The purpose of this research, we want to change or give the evidence to the guidelines for oesophageal cancer treatment, especially in China and East Asia. So in this clinical trial we will answer some questions about the treatment modalities in the immunotherapy era – which kinds of modalities immunotherapy combined with is more better. After this research we will give the answer. But the EFS we still need time to follow up so maybe in one or two years we will finish the median follow-up about the results and after that we will publish it and we will see if those treatment modalities will change the EFS or not.
But for now we can say the pCR rate is very impressive, based on the chemoradiotherapy combined with immunotherapy. In those patients who are sensitive or whose response is very good for the treatment modality we will have the chance or opportunity to get the organ preservation watch and wait strategies.
