We have at ASCO this year, we only have, really, brand new data that has a big impact on either trial design or new studies in two different trials. There is going to be a lot of other very interesting data that impacts our thinking - subset analyses from a number of very important trials, including the TROP-2 antibody datopotamab deruxtecan. Then subset analyses from the Avera trial which looked at giredestrant and everolimus in the second-line hormone receptor positive setting. Very important to understand what treatments patients received after progression. Then there’s additional data looking at subset analyses from ASCENT-07 that looked at sacituzumab govitecan in hormone receptor positive metastatic disease in the first-line chemo setting.  So those kinds of subset analyses, just to name a few, are really important.

The positive trial that will be presented as a late-breaking abstract is VIKTORIA-1, the PIK3CA mutated cohort. We’ve already seen data showing that this PI3 kinase and mTOR inhibitor that’s given intravenously three weeks on, one week off, is very effective in patients who do not have evidence of a tumour PIK3CA mutation in the first part of VIKTORIA-1. This second part looked at patients who had mutations in PIK3CA and used the same experimental arms, so gedatolisib and fulvestrant in one arm and gedatolisib, palbociclib and fulvestrant in the second arm, so a triplet or doublet. The comparison here, though, was different with alpelisib and fulvestrant being the control arm. We know that there are difficulties in tolerating alpelisib, so it’s going to be interesting to see what the drug exposure was in this subset, but they have a press release showing that both arms significantly improve progression free survival compared to the control arm. I think that’s very important because, as an IV therapy three weeks on, one week off, it does not cause the hyperglycaemia and rash that we see with alpelisib. It does cause stomatitis, however, based on the mTOR effect, but that stomatitis did not result in significant discontinuations of drug in the first part of VIKTORIA-1. So that’s going to be very interesting to see.

The second trial that I think has great impact, although it’s a negative trial, is persevERA that looked at, in the first line, an endocrine sensitive population. That’s a really important distinction because there are other trials that are looking at the first-line endocrine resistant population that’s defined as patients who are relapsing while on or within a year of adjuvant endocrine therapy. In the endocrine sensitive population we expect ESR1 mutations to be less than 5% and doing trials in that setting would require that the oral SERD would be better than an aromatase inhibitor. The background is that fulvestrant was not better than exemestane in two randomised trials but it was significantly better in patients who had an ESR1 mutation. This was in the second-line setting and it really opened the whole world of studying ESR1 mutations in pre-treated hormone receptor positive breast cancer. 

So persevERA randomised patients in the first-line setting to receive the oral SERD giredestrant plus palbociclib versus an AI and palbo and showed, by press release, no significant difference in progression free survival, their primary endpoint. Giredestrant is very well tolerated and this data was really important because of data from lidERA. lidERA is an adjuvant trial in high-risk, early-stage breast cancer that at just three years showed an improvement in invasive disease free survival and disease free survival with giredestrant versus AI or tamoxifen, they didn’t determine it, but no CDK4/6 inhibitor.  So I think that it’s going to be fascinating to see what happens with switching trials in the early stage setting and the CAMBRIA trial that did include a CDK4/6 inhibitor in a subset of patients, as well as additional trials, the SERENA-4 trial, that’s looking at this same idea with camizestrant in the first-line metastatic setting and the resistant population. Also analyses of ESR1 mutations in the persevERA trial are going to be fascinating and that data is not yet public.

So lots to see at ASCO this year, even though there aren’t maybe the same as many blockbuster studies as we’ve seen last year.