The Impower132 study is a study that compared the combination of chemotherapy and chemotherapy and immunotherapy. The background is that we know that we have in lung cancer an efficacy of the PD-1 and PD-L1 agents with three agents that are already registered in this field in the second line setting. We had several studies presented combining chemotherapy and immunotherapy. Then we were missing data from the combination of atezolizumab with the combination of carboplatin and pemetrexed and also look at some specific subgroups such as never smokers, patients recruited in Asia, patients with older age and so on. Then it’s what has been presented at the ESMO 2018.

How many patients were available in these smaller groups?

Overall 578 patients have been included in this study and the proportion of patients recruited in Asia is the largest that we have to date in this type of study – 25% of the patients recruited in the study. For the never smokers patients it represented 12% of the patients included in the study and for the patients that were older than 65 years it represented approximately half of the patients because the median age was 64 years.

Can you talk about some of the results from these individual groups?

What was interesting in the IMpower132 trial, we demonstrated an advantage regarding the progression free survival with a hazard ratio of 0.60. The overall survival data are not yet mature but there was a numerical advantage with a hazard ratio of 0.81. Then looking at the subgroups, what’s demonstrated in all the analyses that have been done is that there was reproducibility of the activity and the superiority of the combination of chemotherapy based on platinum and pemetrexed and atezolizumab over the standard chemotherapy in all subgroups but the patients with liver metastases at baseline.
Then we had an advantage for the combination in never smokers patients with even a slightly better hazard ratio of 0.49. It’s a population of interest because we know that those patients may have tumours with less inflammation then less chance to have the immune system working, then it was important to confirm that the benefit was there for these patients.
For the patients recruited in Asia we have an even better hazard ratio of 0.42 and an increase by 5 months of the median progression survival from 5 to more than 10 months. I think it’s something that is also important to know because we have a large proportion of patients that were never smokers in these populations even if the patients with EGFR mutated tumour were excluded. We do not fully understand this difference of activity in the Asian patients compared to the patients recruited outside Asia. It may be related to some clinical factors, it’s maybe related to some biological factor and the biological study of all the biomarkers is ongoing.

When can we expect that further analysis to be available?

We expect to have the overall survival data in the first half of 2019 along with probably the whole analysis of the biomarkers in order to better understand what supports the activity in the different subgroups.

In more general terms, what do these findings mean for the successes of PD-1 in lung cancer?

Just before maybe just saying a word about the patients with liver metastasis. I think it’s important because we have the stratification by the presence of liver metastases only in the IMpower studies and we have two studies presented today, the IMpower130 and the IMpower132, that show that there was no benefit for the patients with liver metastases to receive the combination of chemotherapy and immunotherapy. It may be related to various factors, one maybe the high level of VEGF in disease. Then conversely we had the results of the IMpower150 trial that showed that when combining the chemotherapy, the atezolizumab then the PD-L1 inhibitors and the VEGF inhibitors then you can get better results in the patients with liver mets. It’s just a factor that was not fully considered in the past that we should not consider odd when deciding the treatment.

And then on to what this means.

On the PD-L1 inhibition in lung cancer we had several studies in the second line setting, we have now around ten studies in the first line setting, either in monotherapy or the combination of IO plus IO or the combination of chemotherapy and IO with more than five positive trails with atezolizumab. Then we have now a large opportunity of combination immunotherapy for lung cancer patients. But we have to understand what are the patients that benefit the most from this kind of combination, what are the patients that may be treated with only a monotherapy and what are the patients that are resisting very early to this kind of combination and need to be proposed another kind of treatment.