Gedatolisib is an IV PAM, PI3K and mTOR1-2 inhibitor. Alpelisib, as you all know, is a single-target PI3 kinase inhibitor. This abstract provides findings for the PIK3CA-mutant cohort on VIKTORIA-1. Prior findings have already shown improvement in PFS in the PIK3 wild-type cohort for gedatolisib triplet and doublet vs standard of care. And so this abstract is essentially showing us the data in the PIK3CA-mutant population.

Patients were eligible for this trial with advanced or metastatic hormone receptor–positive breast cancer who had progressed on prior CDK4/6 and AI in the first-line setting. Then they were randomized to gedatolisib with palbociclib and fulvestrant, so the triplet arm, vs a gedatolisib/fulvestrant doublet arm, vs standard-of-care alpelisib with fulvestrant.

VIKTORIA-1 met its primary endpoint and showed PFS of 11 months for the gedatolisib triplet and 11.3 months for the gedatolisib doublet vs 5.6 months for the alpelisib doublet. So for patients receiving gedatolisib in the triplet or doublet fashion, it took nearly twice as long for their cancer to grow compared to a patient on alpelisib with fulvestrant.

On this trial, we did see consistent safety data for the individual agents in the trial, and the discontinuation rate for gedatolisib combinations due to AEs was pretty low, at less than 4%. Gedatolisib arms showed all-grade hyperglycemia of 11% and 15%, and a low rate of grade 3 hyperglycemia events. One of the main AEs we need to watch for with this agent is stomatitis, this was seen at 61% for gedatolisib, and grade 3 events for this were 16% in the triplet and 5.8% in the doublet arm.

So what are some special considerations for APPs using gedatolisib in the future? So gedatolisib is an upcoming possible new option to consider for our patients after progression on first-line CDK4/6 and aromatase inhibitor therapy. We may not need formal NGS testing to treat our patients with this agent since we've seen improvement in PFS in the PIK3-mutant and wild-type patients. This study shows no evidence that a three-drug combination with palbo is better than a two-drug combination of just gedatolisib and fulvestrant. Ultimately, adding a CDK4/6 inhibitor adds more toxicity.

Also, administration is unique for gedatolisib compared to other PAM pathway agents in that it is given intravenously weekly for 3 weeks on and 1 week off. So in general, studies show that about 90% of cancer patients do prefer PO drugs. We also have to consider that patients' proximity to clinic, family support, and ability to come for ongoing weekly treatments when we're considering what type of PAM pathway treatment we're choosing for our patients.

I think the utility of this drug will be seen more so in our wild-type population who have more limited options. And we also will probably consider this for patients maybe that have had a prior gastric sleeve or some sort of potential GI absorption concern and for those with intolerance to other PAM pathway agents.