Advancements in Oncology, an innovative, panel-based event hosted by The Oncology Brothers, Rohit Gosain, MD, and Rahul Gosain, MD, MBA, featured an esteemed cast of thought-leaders in breast, gastrointestinal, genitourinary, and lung cancers.
Margaret Gatti-Mays, MD, MPH—who kicked off the event’s first panel discussion by talking about the optimal chemotherapy regimen for patients with hormone receptor-positive disease—next detailed treatment options for patients in the metastatic setting.
“Two or 3 years ago, we did not have many options [in the metastatic space],” said Dr. Rahul Gosain. “Now, we’ve seen so many more approvals, elacestrant, sacituzumab, and T-DXd. We have data from a few more studies, including INAVO120. We’ve always wondered how the field is going to change for CDK4/6 inhibitors post-MONARCH.” He asked Dr. Gatti-Mays, “What’s your go-to CDK4/6 inhibitor right now? Walk us through these data and how they are going to change your practice.”
Dr. Gatti-Mays stressed the importance of tailoring the treatment plan to the individual patient and then noted her CDK4/6 inhibitor of choice. “How I approach hormone receptor-positive metastatic breast cancer really depends upon the patient who’s sitting in front of me, not only in terms of the patient’s performance status, physiologic age, and functional age, but in general, starting with a CDK4/6 is pretty clear at this point. I tend to favor ribociclib given the survival data and the survival benefit that we’ve seen, which have not necessarily panned out with palbociclib or abemaciclib.”
Given the plethora of treatment options now available, Dr. Gatti-Mays expressed the importance of “making sure that we are looking for actionable mutations.” Specifically, based on the type of mutation, Dr. Gatti-Mays said, “If it’s PIK3CA, I tend to use alpelisib with fulvestrant. Obviously, capivasertib is also an option that can be used with fulvestrant. I favor alpelisib just because of the survival data we’ve seen. Also, some of the subgroup analyses with capivasertib showed that maybe in the PIK3CA subgroup, it was not quite as strong as the PTEN or AKT.”
In those patients who have a PTEN or AKT gene mutation, Dr. Gatti-Mays stated that “capivasertib would be the choice. In those patients who have an ESR1 mutation, elacestrant is obviously an option. The other thing we often consider with those patients with an ESR1 is aromatase inhibitors [AIs] may not be working well. If a patient is on a CDK4/6 with an AI and develops an ESR1 mutation, I often ask myself, ‘Is this a resistance to the AI itself?’ In that case, I would potentially consider a CDK4/6 to follow but using fulvestrant instead of an AI. Sometimes that decision really depends upon the patient in front of me. There’s not necessarily a right or wrong answer.”
With the myriad options available, Dr. Gatti-Mays explained how she breaks down the treatment plan for her patients. “We note that there are a lot of options. If they can’t tolerate the therapy, we have a backup plan. If patients don’t have an actionable mutation, then I tend to favor everolimus with fulvestrant or an AI depending on if they have an ESR1 mutation or not.”
Dr. Gatti-Mays also noted she tries to exhaust the available endocrine options before initiating chemotherapy. “Historically, we’ve said 2 to 3 endocrine options before we move to chemotherapy. I often find myself doing 3 to 4 at this point. That’s an area of great need, and most of these trials with the targeted therapy are in the second-line setting. But as we have different options, are we still seeing benefit in later lines and specifically before we get to chemo?”
Noting the survival data on ribociclib and abemaciclib, Dr. Rohit Gosain asked, “How are you going to be maneuvering, especially when the survival is questionable here?”
Dr. Gatti-Mays said the data were interesting. “When you look at the [INAVO120 trial] population, 60% or so were on palbociclib, about a third were on ribociclib, and 8% or 9% were on abemaciclib. Many oncologists reach for ribociclib first. That being said, this is a very interesting combination. Patients with PIK3CA mutations can do very well on CDK4 therapy.” She went on to caution that the combination comprises “3 drugs instead of 2, and every time you add drugs, you add potential side effects.”
Dr. Rahul Gosain ended the second part of the discussion on the topic of biopsy. “You prefer liquid biopsy,” he said. “As community oncologists, we’re so used to the idea of tissue as the issue, and we’re chasing the actual solid tissue. But it’s been endorsed that, in breast cancer, we should perhaps rely on liquid tissue. It’s faster and allows you to better appreciate mutations like ESR1.”
According to Dr. Gatti-Mays, while tissue biopsy is still the industry standard in some aspects, liquid biopsy yields more detailed information. “Tissue is still my gold standard for looking at our canonical receptors (estrogen, progesterone, HER2). But we’re also starting to appreciate how heterogeneous some of these tumors can be. Depending on which tumor you biopsy, you may see an actionable mutation, whereas when we do a liquid biopsy, we get a collection of all the tumors that are shredding the proteins. Blood, especially for the actionable mutations, is much more accurate, and several studies have shown that. An initial tissue biopsy obviously is needed to confirm metastatic diagnosis. After that, liquid biopsy provides more information and is easier on patients.”
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