COMMENTARY

Real-World Metastatic Breast Cancer Treatments Fall Far Short of Pivotal Trial Outcomes

Kathy D. Miller, MD

Disclosures

November 11, 2021

This transcript has been edited for clarity.

Hi, everyone. It's Dr Kathy Miller from Indiana University. I came across an article in JAMA Oncology this July that is both sobering and not terribly surprising. I want to make sure you have a chance to see it and think about it as well.

This study looked at a comparison between patients treated in the real world — as in, not part of a clinical trial — compared with the results reported in clinical trials with the same baseline therapy. This is work from Dr Christopher Booth and his colleagues in Ontario, and they evaluated 795 patients treated with pertuzumab-based regimens for metastatic HER2-positive therapy and 506 patients treated with trastuzumab emtansine (T-DM1), also for metastatic HER2-positive disease.

In the pertuzumab group, median overall survival was 43 months, which was significantly shorter than in the pivotal trial. In the T-DM1 group, median overall survival was 15 months, also significantly shorter.

We should not assume that this means the clinical trial results were wrong, done incorrectly, or somehow fraudulent. The real world is different. Patients tend to be a little bit older and have more previous therapy. There was less fidelity to the rigors of organ function and all of the details that go into patients who are treated in clinical trials.

We've known about the difficulties with selection bias in clinical trials for a long time, and this analysis simply reminds us of the impact of that selection bias, intentional and unintentional, and how the results from those clinical trials compare when we move into the much broader population. It also means that analyses like these will continue to be important.

One of the things that the pandemic may allow us to do is think about doing clinical trials in more of a real-world setting with less rigid selection criteria, more flexibility, and focused on those key end points of overall survival. If we are able to do that, the results might not fall so far when they go from the rarefied air of clinical trials into the clinic patients whom we see every day.

Take a look at this article in JAMA Oncology. It's a fascinating and sobering read.

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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