We presented the results of the VIKTORIA study. VIKTORIA was a two-part study, study 1 was conducted in patients with hormone receptor positive, HER2 negative, PIK3CA mutation wild-type breast cancer and we presented and published those results previously. Study 2 is a study looking at hormone receptor positive, HER2 negative metastatic breast cancer in PIK3CA-mutated breast cancer.

Could you outline the methodology?

VIKTORIA was an open-label phase III clinical trial, there were three treatment arms. The first arm was gedatolisib, which is a PI3 kinase mTOR inhibitor, it hits all the type 1 PI3 kinase isoforms, as well as mTORC1 and mTORC2. We looked at gedatolisib in combination with fulvestrant and palbociclib, that’s the triplet regimen. We also looked at it as a doublet regimen, gedatolisib with fulvestrant, and we compared that to alpelisib/fulvestrant which is the standard of care for patients with PIK3CA mutated ER+ breast cancer in this setting.

All of the subjects, all of the patients who enrolled in this study, had previously received a CDK4/6 inhibitor with endocrine therapy and aromatase inhibitor, and had experienced disease progression. Patients were randomly assigned in a 3:1:3 ratio to the triplet or the doublet or the alpelisib/fulvestrant control arm.

What did you find?

We found that patients treated with the gedatolisib triplet compared to the control arm had a statistically significant and clinically meaningful improvement in progression free survival. It was a doubling of the progression free survival. The hazard ratio was 0.50.

We also observed that in patients receiving the doublet of gedatolisib/fulvestrant versus alpelisib/fulvestrant, there was a similar about 50% reduction in the risk of progression or death, so the hazard ratio was 0.51. Again, it looks statistically significant and very interesting.

We also saw at an early glimpse of the overall survival endpoints that overall survival is trending towards improvement with the gedatolisib arms, the triplet and doublet, although the data is less than 50% mature and will need to follow up.

In terms of safety, the gedatolisib-based regimens did appear to be safer in general than alpelisib with lower rates of hyperglycaemia, diarrhoea and rash than seen with alpelisib. We did see about a 60% rate of stomatitis in our patients, however, most of it was grade 1 or grade 2 and resolved by the third cycle.

So in summary, this study showed a really quite compelling improvement in progression free survival by using gedatolisib-based therapy in patients with PIK3CA-mutated ER+/HER2- metastatic breast cancer after a CDK4/6 inhibitor-based therapy.

What impact could these findings have?

This is actually the longest progression free survival and objective response rate that’s been observed, to my knowledge, in a patient population with hormone receptor positive metastatic breast cancer being treated in the second-line setting with an endocrine-based therapy. The objective response rate was almost 50% in patients treated with the triplet. So our hope is that this will receive regulatory approval and be available to patients.

When you combine these results with the results of study 1 which looked at the triplet regimen or doublet regimen in patients with PIK3CA wild-type disease, that study also was very positive in terms of meeting its primary endpoints. So the hope for our patients is that these regimens will be available to patients and approved later this summer.