No benefit for adjuvant durvalumab in completely resected NSCLC

Prof Glenwood Goss - University of Ottawa, Ottawa, Canada

At the time of initiation of this study, which was ten years ago, checkpoint inhibitors had been shown to improve survival in metastatic non-small cell lung cancer, both in the first- and second-line setting. However, at that time we only had adjuvant chemotherapy for the additional treatment of early stage non-small cell lung cancer. But with adjuvant chemotherapy at least 60% of patients still relapsed and died from the disease. So there was a need to improve the outcomes of this potentially curable population with early stage disease. As a consequence of the results in the metastatic setting with PD-1 and PD-L1 inhibitors we initiated this trial with a PD-1 inhibitor called durvalumab.

What was the study design?

The study is a double-blind randomised phase III study of durvalumab versus placebo in stage 1b to 3a non-small cell lung cancer.

What were the results you were presenting?

We were presenting the disease free survival results from this trial. This is the final analysis of the disease free survival results. We are presenting the results in the EGFR wildtype population.

The primary endpoint of the study is disease free survival in those patients whose tumours were EGFR wildtype and had a PD-L1 score of 25% or greater. So that was the primary endpoint. There were five other secondary endpoints which included disease free survival in the population whose tumours had a PD-L1 score of 1% or greater and then in all the EGFR and ALK wildtype patients, regardless of their PD-L1 status. Then there were further secondary endpoints of overall survival.

We are reporting on the three populations, the primary endpoint, and the two subpopulations in the EGFR wildtype population which represents 1219 patients. We registered 1827 patients on trial, we randomised 1415 and 1219 of those patients were EGFR wildtype and that’s the group we’re reporting on.

The findings are that for the primary endpoint, which was disease free survival in the patients whose tumour was EGFR wildtype and had a PD-L1 score of 25% or greater, there was no significant difference between the durvalumab arm and the placebo arm. As far as the two secondary endpoints which we reported on the results were similar - there was no statistically significant difference for that group of patients whose tumours were EGFR wildtype and had a PD-L1 score of 1% or greater or in the overall group who were EGFR wildtype regardless of PD-L1 status there was no statistically significant improvement in outcome on durvalumab versus placebo. In the subgroup analysis there was no statistically significant difference between any of the important subgroups that we looked at.

What was the safety profile?

The safety profile was similar to that seen in other large randomised phase III studies with durvalumab. It was very tolerable and there were no unexpected side effects.

What is the wider impact of this study?

It has left the field slightly confused because we have three large adjuvant randomised studies. The first one was the IMpower010 study with atezolizumab, the second was the PEARL study, which was the EORTC study, with pembrolizumab and now we have the Canadian Cancer Trials Group study, BR.31, with a negative result. So we have a highly positive study, a somewhat positive study and now a negative study.

It leaves us wondering what the role of checkpoint inhibition is in the adjuvant setting in early stage non-small cell lung cancer. The field is moving and so there have been a number of trials of neoadjuvant treatment and then what is known as perioperative treatment where the patient gets both neoadjuvant treatment then resection and then adjuvant treatment. We know, for instance, the AGEAN trial with durvalumab, which is the drug that we used in our study, is positive. We also know that the PACIFIC study which was in stage 3 disease with durvalumab as adjuvant treatment was positive. So it leaves us in a quandary as to what treatment to recommend.

So my advice to physicians would be you have to take into consideration the patient and the patient’s characteristics. Then you have to explain to the patient the results of the three trials. Following that explanation the patient can then make an informed consent as to what treatment they should have in the adjuvant setting.