SERENA-6 Explained for Breast Cancer

[00:00:00]I welcome you to this year but YouTube video that's going to focus on a recent trial that came before the FDA referred to as Serena 6. Now with respect to Serena 6, the concept was basically in a patient population that had hormone sensitive HER2 negative metastatic breast cancer who were being treated with an endocrine therapy which would be standard. What if you found that the patients developed a mutation before there was evidence of clinical disease progression and at that juncture without evidence of the disease progressing on imaging, change the therapy to address that molecular change that was evolving in the tumor. Might that affect the overall outcome of patients? And in the patients where there was what we call an ESR1 mutation developing which would have been detected in the circulating tumor DNA obtained by blood sample, patients were randomized to continue on their current therapy because again, there's no evidence that the disease had changed on any of the x-rays. Or they were switched to a newer anti-hormone therapy in this case referred to as camizestrant. And that drug camizestrant is one of many drugs that are in development or have recently been approved that appear to be active against patients who harbor these ESR1 mutations. But the basic idea was could we have a jump on when metastatic disease was changing and by changing therapy might we impact on the overall outcome of patients. So what the trial demonstrated was in the patients who developed an ESR1 mutation who switched to the new therapy camizestrant rather than continuing on the standard endocrine therapy, the time until the disease progressed was longer. And by that I mean the time until there was evidence on x-ray that the disease was changing was longer in the patients who had an early switch. There was There's evidence at this point that overall survival had been changed in any way.

[00:01:59]It's still immature. And one of the criticisms ultimately leading to the FDA not approving this strategy and this drug in particular is that we don't use standard endpoints in this trial. And it would have been precedent-setting to do so without evidence that you were improving the overall survival of patients. So in other words, we don't know that time until disease progression translates into an improvement in survival. It may have been [snorts] that patients who stayed on the standard endocrine therapy and at the time when there was clinical evidence of disease progression, if they had received camizestrant at that point, the outcome may have been the same across all the patients involved in this [music] trial.

[00:02:41]So we don't know the answer to those questions and we won't because the way the trial was designed failed to take that into account.