New First-Line Treatment: Metastatic Triple-Negative Breast Cancer with Dr. Sara Tolaney

Those are big questions.

So, um, [chuckles] I will say, uh, maybe just to take a step back, um, you know, when we think about treating metastatic triple-negative breast cancer, I think it's really critical that we think about making sure we're making the right treatment decision for our patients as that very first therapy that they're getting.

And for a while now, we've had antibody drug conjugates available for metastatic triple-negative disease, and the first one being sacituzumab govitecan, which had been approved several years ago, but it was for patients who had pre-treated metastatic triple-negative breast cancer.

So, um, in essence, it got approved for patients who were getting their second or later line treatment and in fact showed that it kept cancer controlled almost three times as long as standard chemotherapy.

It doubled survival.

Um, so it was a huge impact for patients, um, compared to our standard treatments at the time.

But I think our challenge is that not everyone who has metastatic triple-negative breast cancer to date has actually been able to get to a second line of therapy, and that is really a horrible statistic, right? It means that a lot of our patients who start first-line triple-negative therapy have such deterioration in health or die from their breast cancer that they can't even get to a second line of therapy.

So it is so critical that we do much better for our patients with triple-negative breast cancer.

We need to move our effective therapies into that upfront setting.

And so we knew again that antibody drug conjugates work great, but they were not tested in the first line.

And so there's obviously been a lot of interest to see how we could best move these agents earlier.

And so when we first treat patients with metastatic triple-negative disease, one of the things we need to know is does the tumor have the PD-L1 receptor on it? It-- This receptor is seen in somewhere between twenty-five to forty percent of tumors in patients with metastatic triple-negative breast cancer.

Um, so it's not everyone.

It's a little less than half of the patients who will have this receptor present.

But we know having this receptor is a sign that your cancer is trying to evade the immune system.

It's trying to hide and not let your immune system kill your cancer cell.

Um, and so we, in someone who has a PD-L1 positive tumor for a few years now, we've standardly used chemotherapy with a checkpoint inhibitor, so specifically pembrolizumab.

And that combination of augmenting the immune response with chemo has improved survival outcomes for patients with metastatic triple-negative disease.

So really important to know that your tumor has that receptor, so you can get immunotherapy.

Um, but then we thought, well, [chuckles] if chemotherapy and immunotherapy is so effective, why not substitute that chemo with an antibody drug conjugate? And we knew ke- that antibody drug conjugates were better than chemo head-to-head, and we also had some data to suggest there might be synergistic activity between the antibody drug conjugate and immunotherapy.

You could think that if you're killing the cancer cells so much better by giving an antibody drug conjugate, you're gonna release all these antigens that your immune system can then recognize as not belonging, and then these drugs can work together to kill the cancer cell even better than chemo immunotherapy.

At least that was our hypothesis, right? [chuckles] Um, and so that's a long way of saying we decided to do this trial called ASCENT O-four, um, which looked at the combination of sacituzumab and pembrolizumab and compared it to chemo pembrolizumab in patients as their very first treatment for metastatic triple-negative disease if they had a PD-L1 positive tumor.

And we found that the combination of sacituzumab and pembrolizumab did much better than chemotherapy and pembrolizumab at keeping their cancer controlled for longer.

Uh, so we saw a significant improvement in progression-free survival going from about seven point eight to eleven point two months.

And so, um, really, I think will become, I hope, a new standard of care treatment.