My name is Sara Tolaney. I'm a breast medical oncologist at Dana-Farber Cancer Institute in Boston and chief of our breast oncology program here. And I have an interest in drug development and really trying to make sure we're improving outcomes for our patients while balancing that with toxicities of therapy.
ESMO 2024 was an exciting conference in breast oncology, where we did see some new and emerging data, which I think will have some changes in our practice pattern.
There are three studies that I'd like to highlight because I do think they will have some impact on our practice patterns.
The trial that I think we’re all familiar with, which looked at the use of preoperative pembrolizumab in patients with early-stage triple-negative breast cancer.
We had already seen data that demonstrated that adding pembrolizumab to chemo improved pathologic complete response rates. But also very importantly, this translated into significant improvement in event-free survival. And so, it has been standard of care to use pembrolizumab for stage 2 and 3 breast cancer patients. However, what we were all wondering was, will these data actually translate into an overall survival benefit?
And what we saw at ESMO this year was, in fact, it did -- that not only are we improving PCR and EFS, but we are also having a significant improvement in overall survival. I think really solidifying the fact that pembrolizumab should be standard of care in the preoperative setting for early-stage triple-negative patients.
The second trial that I think is very informative was the Destiny Breast 12 study.
This was a really unique trial because it did investigate the use of trastuzumab deruxtecan in patients who have metastatic HER2-positive breast cancer either with or without brain metastases. And I think we've all been trying to understand what the efficacy of Tdxd is for patients who have brain mets, because we know about 50% of our patients with metastatic HER2-positive breast cancer will develop brain metastases over their lifetime. So addressing optimal treatment strategies for this group of patients is really very critical. And we were all skeptical about whether a large drug like an antibody drug conjugate could penetrate into the blood brain barrier and have efficacy within the CNS. And to date, we've only seen small studies that have investigated its benefit in the CNS. But this study looked at about 250 patients with brain metastases that were HER2-positive and found that there was over a 17-month progression-free survival and about a 70% intracranial response rate. This is the highest level of efficacy we have seen for any agent in patients with HER2-positive brain metastases.
So in my mind this these data really solidify that Tdxd should be standard of care for patients who have metastatic HER2-positive disease in the second-line setting. And does include patients who may have CNS involvement.
The third trial that I thought was important to highlight was the Natalee trial.
This trial had looked at the use of ribociclib, an oral CDK4/6 inhibitor in patients with early-stage hormone receptor-positive breast cancer, and was trying to understand if giving three years of adjuvant ribociclib would help improve invasive disease-free survival. The study was a little bit unique because while we have had a CDK4/6 inhibitor approved in this space, abemaciclib, it was specifically for very high-risk patients, whereas Natalee did try to broaden the population of patients that would be eligible for a CDK4/6 inhibitor, not just limiting it to the very high-risk node-positive patients, but also extending it into high-risk node-negative patients. We’ve previously seen data from a second interim analysis as well as the primary analysis where we had seen about a 25% relative risk reduction and a 3% absolute benefit from ribociclib. But now at four years, this is a time point when all patients have completed their three years of ribociclib. And what we saw was about a 30% relative risk reduction in events and a 5% absolute benefit from the use of ribociclib.
And in fact, just today, saw ribociclib received FDA approval for patients with stage 2 and 3 early-stage hormone receptor-positive disease. And I think these four-year data were quite critical for us to be able to understand the continued benefit and whether or not this benefit is seen even after discontinuation of drug. So I do think really does give us a role for ribociclib in the early-stage hormone receptor-positive breast cancer setting.
Well, I think over the last few years, we have seen the most rapid level of drug approvals for patients with breast cancer. And so I think the pace of drug development has dramatically changed, which personally I feel is really exciting because we're getting new agents to patients in a much quicker fashion. And what I do anticipate seeing over the next few years is more and more exciting drugs coming to the table, including seeing more oral SERDs in combination with targeted agents, seeing better drugs that can target the PI3 kinase pathway with less toxicity, with the new mutant selective inhibitors, that we will see more antibody drug conjugates come into the space hopefully that have different payloads than a topo1 payload, which would help us better understand sequencing. And I also hope that we can better understand the use of immunotherapy and that it won't just be restricted to the high-risk triple-negative setting. But I think we will see immunotherapy move into high-risk ER-positive disease and hopefully even see it extend into other populations where immunotherapy has not had a benefit to date. So I think we are going to see a lot of movement in the next few years and hopefully a lot of improvements in outcomes for our patients.
