This study is focussed on patients with squamous cell carcinoma of the oesophagus which is a significant problem in Asian countries, in African countries, in many countries of South America. Although the incidence of squamous carcinoma is going down in Western Europe and North America, since there are so many patients in Asian countries particularly we need to develop better drugs. The current treatment options are very unacceptable and provide minimal or no advantage; chemotherapy has a lot of toxicity. So that was the focus of this particular study.
What was the methodology used in this study?
This was one of the largest and I think this was the largest study in the second line space. So patients with metastatic squamous cell carcinoma were the subject of this particular study. So they had to have a prior therapy which was platinum based. So all eligible patients had to have that and they were randomised to tislelizumab, a novel PD-1 inhibitor, or they received chemotherapy which is the standard of care but in this particular study the investigator had the choice to give whatever chemotherapy they wanted – either paclitaxel, docetaxel, irinotecan was allowed. A total of 512 patients were randomised 1:1, so patients either received tislelizumab or they received chemotherapy, there was no other variation.
The study was conducted not only in Asia but also in North America. Patients were stratified based on the region, based on performance status or whatever chemotherapy the investigator chose to give. So they were stratified according to taxane or non-taxane therapy.
The primary endpoint is very important because it is overall survival advantage. There was an assumption that tislelizumab in all patients, all comers irrespective of biomarkers, will produce an overall survival advantage. The secondary endpoint was to look at patients where the tumour is called a visual CPS, is 10 or higher. So then another endpoint was to really focus on a highly enriched population. So that was the design of the study.
What were your key findings?
The key findings are very positive and it showed overall survival advantage for all comers, irrespective of the tumour characteristics based on the immune profile of the tumour. In all patients tislelizumab produced a significant survival advantage with a hazard ratio of 0.7 and a p-value of 0.001. The twelve month survival rate was 37% for tislelizumab but only 23% for chemotherapy. So that was the primary finding.
An even more striking finding was in a group of patients who had very high PD-L1 expression and this is again by visual CPS score. This is a unique method of looking at PD-L1 expression. Here the hazard ratio was even stronger, it was 0.55 with a very strong p-value. Now the differences at twelve months are very striking – 43% of patients on tislelizumab were surviving compared to only 17%. So, in my opinion, this is remarkable. If you have a highly enriched population tislelizumab is producing the effect that we are looking for.
How can these results impact the future treatment of oesophageal cancer?
Again, we are hoping that tislelizumab will be approved as a second line option for this group of population, metastatic squamous cell carcinoma in second line setting. My hope is that the drug, tislelizumab, will be approved in the United States, in Europe and also in Asia as well as perhaps in South America. So the treating physicians and the patients and their caregivers will have another very striking option available to this group of patients.
Right now in many countries they just get single agent chemotherapy in this setting and they do very poorly. In many countries in this particular setting these patients are not even treated. So just imagine how dramatic an improvement we can achieve with a drug like tislelizumab.
Tislelizumab does come with some side effects so this is something that all of us must realise. However, the significant side effects which are grade 3 or 4 events which are undesirable, the frequency of that is pretty low. So similar to a lot of PD-1 inhibitors, tislelizumab also is accepted or tolerated by most patients. We’re talking about 90% of patients are tolerating it very well but some patients do have undesirable side effects, so something to remember. But the other thing to contrast is this is a non-chemotherapy regimen, tislelizumab is an immunotherapy, so we are comparing immunotherapy side effects to chemotherapy side effects and chemotherapy side effects are highly undesirable. So that’s another discrimination I would like to make.