This trial was designed in 2012 while we were developing taselisib in metastatic breast cancer. We already know that the PI3K pathway is one of the most deregulated in hormone receptor positive HER2 negative breast cancer and at the same time we’ve been working with taselisib. Then we decided to design this new adjuvant trial, the LORELEI trial, testing the hypothesis if we are able to improve the response to endocrine therapy, in this case letrozole, adding taselisib.
I understand that it’s an alpha specific PI3 kinase inhibitor.
Exactly, it’s a beta-sparing because it also targets a little bit the delta unit so the important issue is that it’s sparing the beta subunit of PI3K that seems to be related to toxicity so we call that a specific and potent PI3K inhibitor.
Could we hear some of the outcomes, were endpoints met?
Sure. We designed the trial with two co-primary endpoints. The first of the outcomes was overall response rate. We decided to assess the response rate in this case with a centrally assessed MRI and we achieved our goal to increase the overall response rate. The results of the trial were to increase in the overall population the overall response rate from 39% to 50% with a hazard ratio of 1.55 and a p-value of statistical significance. For the patients with PI3K mutant tumours the difference in response rate was even greater, from 38% to 56% with a ratio of 2.03.
How does that translate into survival if there’s any long-term data?
This trial was not powered for that objective. We powered this trial as a biomarker informative trial so the main results of this trial will be achieved with all the analysis that will be performed later. We collected samples before study entry, at week 3 and at surgery and now we are working on all the analyses on this data. We perform a Ki-67 analysis as well as DNA and RNA sequencing so this will be very informative for the phase III trial that already finished recruitment, the SANDPIPER trial, and with all these trials together will be very informative.
I did note there was some toxicity, including one sudden death from this group.
Yes, unfortunately one patient died in the trial in the taselisib arm but it was a post-menopausal woman with cardiovascular risk factors and investigators did not relate the death of that patient that it was a sudden death with treatment.
So you actually say this is going into the phase III SANDPIPER trial. Do you have high hopes and optimism for the future of this combination?
Yes, of course. The SANDPIPER already finished recruitment this year and we hope to have the first results early next year. So the biomarkers that will be collected in the trial will be very informative also in combination with SANDPIPER. So if SANDPIPER is a positive trial it’s intended to be a registrational trial so we are very happy and we are eager to see those results.
We’ll have to keep an ear out for when those results from SANDPIPER come through. Apart from that that’s all the questions I’ve got; was there anything that we didn’t mention?
No, I don’t think so. I only forgot to mention the second endpoint of the trial - it was the PCR that was not reached in this case but we designed the trial as being positive if one of the each of the two co-primaries were positive. So we achieved our goal.
