I just presented the results of the SUMMIT study which was a multinational non-randomised phase II study of neratinib in patients with HER2 or HER3 mutants. We looked at the effectiveness of neratinib, which is an inhibitor of all the HER proteins, in patients whose tumours had activating mutations in the HER2 or HER3 proteins.

What were your findings?

We found that neratinib was most active in patients with breast cancer, HER2 mutant breast cancer, as well as HER2 mutant biliary and cervical cancers. We found a relative absence of activity in colorectal cancer and bladder cancer. We think that there were really two things that were driving these differences: one is that certain tumour types appear to be more sensitive to inhibition with neratinib as well as different mutation types seen in different tumours. So we think there’s both an effect of the tumour type that the patient has but also the individual HER2 mutation that is seen in that patient. We didn’t see any activity in patients with HER3 mutations and that group is closed.

What are the implications?

We’re moving very rapidly towards combinations of neratinib, either with other HER2 targeted therapy or chemotherapy or endocrine therapy, so essentially drug combinations in these same groups of patients. We really think that’s what it will ultimately require to make a big leap of efficacy in these patients.

Why are we seeing these differences?

What we think we see is that different tumour types have different feedback pathways that overcome resistance to a single agent inhibitor. This has been well documented, for example, in colorectal cancer but it’s probably also operable in lung cancer and a number of other cancer types. So what we really need to understand is the unique biological mechanisms that are driving resistance, either certain mutation types or certain tumour types, and overcome those in a strategic and scientifically driven way.