For Immunotherapy in TNBC, Nab-paclitaxel Is a Must

Kathy D. Miller, MD


September 24, 2020

This transcript has been edited for clarity.

Hi. It's Dr Kathy Miller, back with our second installment of "Good Science That Makes You Think."

Previously, we saw early results of the IMpassion130 trial, a randomized trial of patients with newly identified metastatic triple-negative breast cancer (TNBC) randomized to either nab-paclitaxel alone or nab-paclitaxel with atezolizumab. And we've talked about the design of this trial before. It clearly showed a significant improvement in progression-free survival. The overall survival results — even updated at this [European Society for Medical Oncology (ESMO)] meeting — require caution in their interpretation. There is roughly a 7- to 7.5-month improvement in overall survival in the PD-L1-positive cohort with the addition of atezolizumab. But the study design does not allow us to conclude or to even know if that difference was statistically significant.

Now, at this year's ESMO meeting, we saw the first results of the IMpassion131 trial. It had a very similar design with newly identified metastatic TNBC patients randomized to a taxane or a taxane with atezolizumab. But in this case, the taxane was paclitaxel. And there was no difference [in outcomes] in the overall population, and no obvious difference in the PD-L1-positive population. How could that be? We tend to think of Abraxane as just a taxane in a different packaging; it does not need Cremophor, and therefore it does not need steroids. How could these two different trials using a similar chemotherapy backbone come to such different results?

There are multiple possibilities. Perhaps this is just chance. Perhaps the benefit of atezolizumab is really quite modest so that trials whose results are fairly similar may fall on different sides of a significance boundary, one being reported as positive and one being reported as negative. Perhaps paclitaxel is simply a better taxane — either a better taxane overall or a better taxane when combined with atezolizumab. That is possible. They have been directly compared. There were two small efforts that suggested that nab-paclitaxel was minimally more effective. But multiple other studies did not find a difference.

Perhaps this is a difference in the use of steroids. Nab-paclitaxel was chosen in the IMpassion130 study to avoid the use of steroids. And we commonly use steroid premedication to prevent allergic reactions from the Cremophor with original-recipe paclitaxel. Maybe the steroids eliminate the benefit from immune therapies. That is also possible. It certainly seems plausible.

But let's stop and think for a minute. Many of the regimens in lung cancer, bladder cancer, and melanoma, where immunotherapies are commonly used and where their benefits are magnitudes greater than the benefits we see in TNBC, commonly use steroids as part of their premedications. And yet they work.

I don't have a clear answer for why these two are different. This is going to require much more study, much more careful thought. But like all science, it makes you think. And at this point, it means that if you're going to use immunotherapies in TNBC, it really needs to be with nab-paclitaxel. It should make us very cautious about expanding the results of the IMpassion130 trial to other chemotherapy agents.

As always, I look forward to your thoughts.

Kathy D. Miller, MD, is associate director of clinical research and co-director of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University. Her career has combined both laboratory and clinical research in breast cancer.

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