This transcript has been edited for clarity.
Hi. It’s Dr Kathy Miller from Indiana University. I’m here with you to think a little bit about the San Antonio Breast Cancer Symposium (SABCS) and what we might want to be on the lookout for. There are two studies that I’m particularly interested in seeing.
The first is the most recent neoadjuvant study from our friends from Germany. Many of you know the German Breast Group has done a series of neoadjuvant studies, sequentially improving the outcome for patients with multiple disease phenotypes. This study enrolled patients with triple-negative disease and randomized them to neoadjuvant therapy with a pretty standard anthracycline-, taxane-, platinum-based chemotherapy regimen alone or with atezolizumab.
This is a 1500-patient trial, so it’s very large. While it initially planned to look at both pathologic complete response and event-free survival, the trial was amended a couple of years ago to throw all of the statistical weight and all of the power to the event-free survival endpoint.
Now, why am I so interested in this trial, you might ask. I don’t understand the results that we have from trials thus far. You’ve seen with the KEYNOTE-522 trial— a trial very similar to this study but with pembrolizumab — improvements in pathologic complete response, event-free survival, and now overall survival.
The results with the atezolizumab have been a bit confusing. We saw a previous neoadjuvant trial, not powered or sized for a long-term outcome, with modest improvements in pathologic complete response, but in a full adjuvant trial, the IMpassion030 trial, no difference. Not a hint in sight.
That leaves me with a big question: Is this because there are differences in the checkpoint inhibitors? In breast cancer, is pembrolizumab simply the better drug? Is this a difference in the setting? Is it important that you have an intact tumor at the time of checkpoint inhibition? Do you need to train the immune system on that intact, hopefully dying, tumor to get the long-term benefit?
We simply don’t know, and looking at the results of this trial in the context of those other results could provide some powerful hints as to which of those is really the underlying explanation.
The other trial I’m interested in seeing goes to the complete opposite end of the disease spectrum: the COMET trial in patients with low-risk ductal carcinoma in situ (DCIS). We know that we overtreat patients with DCIS. Dr Shelley Hwang, initially at the University of California, San Francisco , more recently at the Duke Cancer Institute, has been really passionate about getting us to think about whether everybody with DCIS needs to be treated or could some patients with what appears to be low-risk DCIS be observed, either with no therapy or with hormone therapy alone. That led to the COMET trial.
The COMET trial randomized patients with low-risk DCIS to guideline-concordant care. In many cases, that meant surgery. It could have meant radiation, hormone therapy for chemoprevention, or observation. Observation could be with or without chemoprevention based on the patient’s preferences.
Those patients were followed for 2 years, with really important endpoints: How many of them appeared to have progression of their DCIS on imaging, who then went to additional surgery or went to surgery in the observation group, and really importantly, how many of them developed invasive disease in the observation group? That’s the real reason we treat DCIS: to prevent patients from developing invasive disease that could become life-threatening.
This will give us our first look at the COMET trial data, and I think will lead to some really important discussions about longer observation. Is observation an appropriate option for patients with low-risk disease? It certainly will give us really valuable information for those difficult discussions with our patients.
There are always surprises at SABCS. I’ll be back with you after the meeting to talk about the results of these studies and anything else that seems really interesting.
COMMENTARY
Studies to Watch: San Antonio Breast Cancer Symposium
Kathy D. Miller, MD
DISCLOSURES
| December 16, 2024This transcript has been edited for clarity.
Hi. It’s Dr Kathy Miller from Indiana University. I’m here with you to think a little bit about the San Antonio Breast Cancer Symposium (SABCS) and what we might want to be on the lookout for. There are two studies that I’m particularly interested in seeing.
The first is the most recent neoadjuvant study from our friends from Germany. Many of you know the German Breast Group has done a series of neoadjuvant studies, sequentially improving the outcome for patients with multiple disease phenotypes. This study enrolled patients with triple-negative disease and randomized them to neoadjuvant therapy with a pretty standard anthracycline-, taxane-, platinum-based chemotherapy regimen alone or with atezolizumab.
This is a 1500-patient trial, so it’s very large. While it initially planned to look at both pathologic complete response and event-free survival, the trial was amended a couple of years ago to throw all of the statistical weight and all of the power to the event-free survival endpoint.
Now, why am I so interested in this trial, you might ask. I don’t understand the results that we have from trials thus far. You’ve seen with the KEYNOTE-522 trial— a trial very similar to this study but with pembrolizumab — improvements in pathologic complete response, event-free survival, and now overall survival.
The results with the atezolizumab have been a bit confusing. We saw a previous neoadjuvant trial, not powered or sized for a long-term outcome, with modest improvements in pathologic complete response, but in a full adjuvant trial, the IMpassion030 trial, no difference. Not a hint in sight.
That leaves me with a big question: Is this because there are differences in the checkpoint inhibitors? In breast cancer, is pembrolizumab simply the better drug? Is this a difference in the setting? Is it important that you have an intact tumor at the time of checkpoint inhibition? Do you need to train the immune system on that intact, hopefully dying, tumor to get the long-term benefit?
We simply don’t know, and looking at the results of this trial in the context of those other results could provide some powerful hints as to which of those is really the underlying explanation.
The other trial I’m interested in seeing goes to the complete opposite end of the disease spectrum: the COMET trial in patients with low-risk ductal carcinoma in situ (DCIS). We know that we overtreat patients with DCIS. Dr Shelley Hwang, initially at the University of California, San Francisco , more recently at the Duke Cancer Institute, has been really passionate about getting us to think about whether everybody with DCIS needs to be treated or could some patients with what appears to be low-risk DCIS be observed, either with no therapy or with hormone therapy alone. That led to the COMET trial.
The COMET trial randomized patients with low-risk DCIS to guideline-concordant care. In many cases, that meant surgery. It could have meant radiation, hormone therapy for chemoprevention, or observation. Observation could be with or without chemoprevention based on the patient’s preferences.
Those patients were followed for 2 years, with really important endpoints: How many of them appeared to have progression of their DCIS on imaging, who then went to additional surgery or went to surgery in the observation group, and really importantly, how many of them developed invasive disease in the observation group? That’s the real reason we treat DCIS: to prevent patients from developing invasive disease that could become life-threatening.
This will give us our first look at the COMET trial data, and I think will lead to some really important discussions about longer observation. Is observation an appropriate option for patients with low-risk disease? It certainly will give us really valuable information for those difficult discussions with our patients.
There are always surprises at SABCS. I’ll be back with you after the meeting to talk about the results of these studies and anything else that seems really interesting.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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