The combination of cabozantinib and atezolizumab shows moderate activity in treating metastatic adrenocortical carcinoma

Dr Enrique Grande - MD Anderson Cancer Center Madrid, Madrid, Spain

The CABATEN trial is an independent research phase II basket multicohort trial initiated by the Spanish National Taskforce Group for the treatment of neuroendocrine tumours in which we tried to assess the activity and safety of the combination of cabozantinib and atezolizumab, so a TKI and an immunotherapy, in such an orphan disease, a real unmet need, such as the adrenocortical carcinoma.

What was the design of the study?

This is a phase II multicohort basket trial in which we recruited patients into one of the six different cohorts related to endocrine neoplasms. One of them was the adrenocortical carcinomas – locally advanced and metastatic and progressive adrenocortical carcinomas – to the standard of care.

What were the results of this study?

In the CABATEN trial we saw that in the primary endpoint, the overall response rate, two of the 24 patients recruited in this cohort of locally advanced metastatic adrenocortical carcinoma achieved a radiological confirmed response. The thing is, the threshold for the activity that we preplanned was to obtain at least three responses so unfortunately we didn’t meet the prespecified boundary for the activity of cabozantinib and atezolizumab in this scenario.

How do you think these results can impact the clinical treatment of this cancer?

Metastatic adrenocortical carcinoma remains an orphan tumour, unfortunately, since the ‘70s. We don’t have any drug approved by the FDA in this setting. The five year survival of our patients with metastatic disease is less than 15% so definitely this is a real unmet need in daily practice.

The experience that we had before with single agent TKI or with immunotherapy as a single monotherapy unfortunately didn’t show dramatic activity. We aimed to look for some synergism in between cabozantinib and atezolizumab in this scenario but unfortunately we weren’t able to find it. Responses – only two of the 24 patients recruited, 8%, median progression free survival 2.9 months, median overall survival 13.5 months are not really impressive and unfortunately unless we are able to find a biomarker to predict those patients that are responding in advance, unfortunately we cannot really use it in daily practice. I wouldn’t recommend to use that in daily practice.

What is next for this study?

The CABATEN trial has stopped recruitment, we fulfilled the six different endocrine related cohorts that we recruited. We are still performing a follow-up, a longer follow-up, of the clinical data. But the most important thing is that we are now hardly working on the translational research. We really need to try to find this biomarker that may help us to identify those patients that can potentially benefit from this combination.