The Study: If you look at the choices for upfront systemic treatment, you’ll see only a couple of category 1 options: a CDK4/6 inhibitor with either an aromatase inhibitor (AI) or the selective estrogen receptor modulator (SERM) fulvestrant. But what about the combo of AI + fulvestrant? That’s the question asked by this phase 3 trial that randomized roughly 700 post-menopausal women to the AI anastrozole +/- fulvestrant. Initial reporting demonstrated a significant advantage in the primary endpoint of progression-free survival with the combo (HR 0.8), and now we have final reporting of the important secondary endpoint of overall survival (OS). Lo and behold, OS followed the same trend with a significant improvement with the combo from a median of 41 → 48 months (HR 0.8). This was even starker among women with no previous tamoxifen exposure who saw an improvement from 40 → 52 months. Now, an improvement in OS is something even CDK4/6 inhibition hasn’t yet achieved (though, to be fair, the reason is due to a lack of events, i.e., deaths).
Bottom Line: The addition of fulvestrant to an AI for upfront treatment of metastatic hormone receptor(+) breast cancer improves survival over AI alone, but verdict’s still out on how this stacks up to final reporting with CDK4/6 inhibitors. | Mehta, N Engl J Med 2019