Nicholas C. Turner, MD, PhD, on INAVO120: Final Overall Survival Analysis

Here at ASCO, we're presenting the overall survival results of the ANAVO-120 trial. This is a trial for patients with metastatic hormone receptor-positive, HER2-negative breast cancer that has got PIK3CA mutations and specifically for patients that are relapsing on endocrine therapy. We know that this is an aggressive type of breast cancer and we're very much in need of new therapies. And so the ANAVO-120 trial randomized these patients in the first-line setting to the standard of care, which was fulvestrant and palbociclib, or the addition of the PI3 kinase inhibitor inavolisib in the triplet. Inavolisib is a novel PI3 kinase inhibitor. It inhibits PIK3CA alpha, but also it degrades the alpha mutant protein and that probably improves the therapeutic window with inavolisib compared to other PI3 kinase inhibitors. And very importantly, inavolisib is combinable with fulvestrant and palbociclib at the maximum single agent doses. And so what we're doing in that triple combination is we're targeting the estrogen receptor, CDK4/6, and the PI3 kinase inhibitor. And by targeting all of these three key aspects of this type of breast cancer, we're really starting to get really significant efficacy. So in the primary readout of ANAVO-120, we demonstrated that adding in inavolisib substantially improved progression-free survival. And now with longer follow-up, we're also demonstrating that adding in inavolisib improved overall survival with a hazard ratio of 0.67, passing the statistical significance barrier. So that's improving overall survival by 33% on average. A median improvement is 7 months. But we also can look at some other really important endpoints in the study, in particular time to first use of chemotherapy. I mean, this is an endpoint that is very important for people, and the addition of inavolisib delayed the time to chemotherapy on average by almost two years. Now why are we seeing such a big improvement in the study? Partly it's that first-line efficacy substantially improving PFS by over half, as well as a substantial improvement in the response rate. And that of course carries through to delaying time to chemotherapy, but also because we're seeing such a reduction in tumor burden with the triplet that also enabled people in the second line to avoid chemotherapy more often. And it's all translated through to that almost doubling in time to chemotherapy. So this is potentially a really important new treatment option for these patients who've relapsed on endocrine therapy with PIK3CA mutant breast cancer.