So IMvigor130 is a big phase III randomised study really testing what was the most important concept in first line treatment of metastatic urothelial cancer at the time when the study was designed, which was should patients receive platinum-based chemotherapy like we’ve been doing for decades, should they receive immune checkpoint blockade alone with atezolizumab or should they get the combination? The co-primary endpoints of the study were progression-free survival in the comparison of chemo plus atezolizumab versus atezolizumab, and then overall survival. The PFS endpoint was met, statistically significant per the pre-specified p-value threshold; that has been published. 

Overall survival has now gone through a series of interim analyses and now the final analysis. There was a trend at each interim analysis for a benefit with chemo plus atezolizumab versus chemotherapy, but the pre-specified threshold for statistical significance had not been met on the interim analysis. So now we see the final analysis’ hazard ratio is 0.85, the upper bound of the confidence interval is 1.0, so the pre-specified p-value threshold is barely missed. So we don’t technically see a statistically significant improvement by giving chemotherapy with atezolizumab versus chemotherapy alone. That said, there’s some very interesting hypothesis generating data from the study, which is that the choice of chemotherapy backbone might matter, and that if one receives cisplatin-based chemotherapy with atezolizumab, that might be where the benefit is being seen with this combination. So that’s a concept that will be tested further in subsequent studies. 

What are the next steps?

The next steps really are to better understand the impact of the chemotherapy backbone, and there’s a large translational research programme around trying to understand the immunomodulatory effects of that cisplatin versus carboplatin backbone. Then there are future trials designed that will really test the concept whether or not immune checkpoint blockade with cisplatin-based chemotherapy impacts outcomes, rather than a mixed population like the current generation of studies that have recently read out.