Transcript:Tiffany Traina, MD: Some of the new targeted therapies that are in development—and more specifically, some of the recent checkpoint inhibitors—have really offered increasing hope for our patients and our physicians to be able to offer therapies that are not just improving response rate and progression-free survival but really making an impact in overall survival, and that’s tremendously encouraging for the community.
The IMpassion130 trial is a large randomized phase III study, placebo controlled, in women with first-line metastatic triple-negative breast cancer. And this study involved nab-paclitaxel [nanoparticle albumin-bound paclitaxel] plus/minus atezolizumab, a checkpoint PD-L1 [programmed death-ligand 1] inhibitor. The primary endpoint was actually a coprimary endpoint of progression-free survival [PFS] and overall survival in both the intention-to-treat [ITT] population and a prespecified PD-L1—positive population.
So there are a couple of key patient characteristics of women who were on that clinical trial. The disease-free interval of 12 months was a key eligibility criterion. So recognize that these patients could not have received chemotherapy for metastatic disease, and they needed to have more than a year since their adjuvant treatment. Another point to be aware of is that almost a third of the patient population had de novo metastatic breast cancer. So these women are very chemotherapy naïve, including in the early stage setting. About 50% of these women had prior exposure to taxane chemotherapy, and that is 1 of our most active agents in breast cancer and still a standard of care in triple-negative breast cancer.
The trial endpoints were actually quite encouraging. So the primary endpoint first analysis was progression-free survival in the intention-to-treat population, and that met statistical significance of about a 20% improvement in median PFS. What was even more exciting was the results for the PD-L1—positive subset. Now I should spend a few moments talking about PD-L1 positivity. That differed in this study. So here PD-L1 testing was performed with Ventana SP142 antibody. And the definition of PD-L1 positivity was anything greater than 1% staining in the immune cell. All right, that differs from some of the other checkpoint PD-L1 testing in other tumors and even other breast cancer trials.
So in the overall intention-to-treat population, 41% of patients had PD-L1—positive tumors. So when we now looked at the trial results in the PD-L1–positive subset, median progression-free survival increased from about 5 months to 7.5 months, and that was a hazard ratio of 0.6, and that was statistically significant. So there were both a numerical improvement and a quite significant 40% improvement in progression-free survival for those with PD-L1–positive tumors.
There were then some additional analyses for overall survival [OS], and there was an interim OS look in the ITT population. Numerically, there was perhaps a slightly longer median overall survival in the PD-L1—positive subset of about 10 months. However, the trial is not statistically powered to look at overall survival in that PD-L1–positive subset. So while it is compelling and interesting, I think you’ll see that the recent FDA label is driven by the progression-free survival advantage seen.
The addition of atezolizumab to nab-paclitaxel [nanoparticle albumin-bound paclitaxel] did not appear to increase adverse events above and beyond what we would expect from nab-paclitaxel [nanoparticle albumin-bound paclitaxel] alone. There is clearly concern about adverse events of special immune interest in any of these checkpoint inhibitors. And so the discontinuation rate of atezolizumab related to adverse events was double that of chemotherapy alone. But when we look at important concerns with immune-related adverse events, there was really no increase in autoimmune hepatitis over the nab-paclitaxel [nanoparticle albumin-bound paclitaxel] arm alone. There were very uncommon rates of pneumonitis. And probably the most common things observed were hypothyroidism and hyperthyroidism of any grade over that of what was seen with nab-paclitaxel [nanoparticle albumin-bound paclitaxel].
Transcript Edited for Clarity.