Value-based Considerations of CDK4/6 Inhibitors in the Treatment of Metastatic Breast Cancer - Episode 17
Experts in breast cancer management discuss how the COVID-19 pandemic has affected conventional procedures, and measures taken to ensure patients still receive effective treatment.
Bruce Feinberg, DO: We’re in this unusual moment now with the pandemic, and there’s been quite a bit written about the fact that clinical trials are being put on hold, and it makes sense. Of course, you’ve got a toxicity profile that you’re not quite sure how to incorporate, so it makes sense from a drug development perspective and then bringing patients into clinic for surveillance. and it is in their best interest or not.
But I am curious to what extent the pandemic has altered the care of your patients, and is it something that has changed even the prescribing patterns, where an oral agent is preferred because you can do telemedicine with them or changing the frequency with which you monitor them? How often are they coming in, because blood work and a physical exam is not that critical? But if you could speak to the pandemic and its impact on management of breast cancer patients, I think would be helpful for the audience.
William J. Gradishar, MD: I would just make a couple of broad comments at the outset. One is, we separated into those with early-stage disease and then obviously metastatic disease. And what most centers have experienced, particularly where there’s significant COVID-19 [coronavirus disease 2019] activity, is that screening has been stopped, elective surgeries have been delayed, patients who were going to get surgery have been put off. So, in those circumstances, particularly where somebody has an early stage breast cancer, who’s ER-positive, who didn’t get surgery, we may start them on endocrine therapy instead of giving them chemotherapy. For the patients who are triple-negative, who have HER2-positive disease, we have been treating them. We continue to treat them. But the surgery issue and radiation, they’ve been pushing back, too, and delaying things.
With respect to metastatic disease, if patients are on treatment, they continue treatment. If patients are starting treatment and we have an option of using something less toxic, I think we would prefer that, particularly in older patients where we can do everything we can to keep them away from the hospital and certainly out of the hospital as an inpatient. That would be the desired thing.
With respect to the topic today, we have continued to use CDK4/6 inhibitors. We haven’t stopped doing that. The degree of neutropenia that we see with ribociclib and palbociclib is not so low that we’re worried for most, the vast majority of, patients that they’re going to end up in the hospital. Abemaciclib with the GI [gastrointestinal] symptoms, again we may preferentially again choose one of the others just so we don’t have any diarrheal issues in an older patient that prompts them to come to the hospital. But I think we’ve made some allowances for what’s going on, but for the patients undergoing treatment we’ve continued it.
Bruce Feinberg, DO: Joyce, anything to add on the pandemic and the changes in practice?
Joyce A. O’Shaughnessy, MD: I totally agree with everything Bill said. Patients are worried. A patient yesterday was calling the office, just really wanting to stop her CDK4/6 inhibitor. She’s actually on an adjuvant clinical trial. She’s doing perfectly well but very worried about myelosuppression. Interestingly, she’s not very myelosuppressed at all. So there’s a lot of reassurance necessary. But, if somebody has metastatic disease, I have patients who have to run grade 3 neutropenia with neutrophil counts chronically under 1000 on some of these agents, palbociclib, ribociclib.
But I have found that those reductions in some patients don’t substantially impact the neutropenia and you’re eroding your dose. And patients do well for many years sometimes on these agents. I’ve chosen to stay the course because thankfully with the CDK4/6 inhibitors, though there can be grade 3 and rarely grade 4 neutropenia, it is about a 1% chance of translating into a febrile neutropenic episode and the death rate is negligible, if not zero. So there is a great margin of safety there, I feel, but we do have to reassure patients. There is a lot of concern.
Bruce Feinberg, DO: Speaking of concerns, Bill, back to you. Institutionally, I don’t know if this has been reported or studied but, certainly nationally, all across cancers screenings are down. Mammograms are down. Are you concerned about both the patient with palpable disease as well as the patients not getting screening mammography, that there’s going to be a surge of more advanced-stage patients coming into clinic at some point in time as lockdowns lessen and people’s fear of the hospital reduces?
William J. Gradishar, MD: Well, we think there’s going to be a significant uptick in the summer as screening comes back online. The example you gave of somebody with a palpable lesion, those are patients that we’re going to start evaluating and working up. And, if they required some form of therapy, even if it’s preoperative endocrine therapy, we would start that. But, with respect to unknown cases that exist in that screening pool that we’re not even evaluating, we’re not, hopefully, going to be pushing them off for more than a couple months. But it’s possible somebody could have aggressive disease in that group and get worse over that period of time. We’re starting to open up a little bit with screening, just starting in the next week or so. But that’s already 2 months of screening that hasn’t been done in a very large center. So there’s a large population of breast cancer that exists in there, and we’re going to be busy once the ORs [operating rooms] start opening up again.
Bruce Feinberg, DO: And Steve, you’ve got not only a large population but you’ve got a hot spot that significantly impacts that population. Are you able to model what you think is going to be happening and how to, in any way, prepare for that?
Steven Peskin, MD, MBA, FACP: The short answer is no. Return to care is happening. Actually, listening to the radio this morning, 1 of our leading oncologists here in New Jersey was talking about return to care for his system with cancer care. Women with breast cancer who have been anxiously waiting for their surgery, it’s beginning to happen. I was talking to a leader in GI [gastrointestinal] oncology and he was saying we’ve seen this trend downward in colon cancer for the better part of a decade, Bill or Joyce, maybe longer than that and his concern that with lack of screening that’s going to have a negative consequence on that particular type of cancer. Mammography was mentioned earlier.
So we don’t have anything yet. I mean, we’ve just been kind of making our way through the crisis and making policy changes to allow for telephone in addition to synchronous audio and video. Certainly, the oncology community, like the primary care community, like the dermatologists, has embraced telehealth, so that’s been a big factor to provide some level of longitudinal care, although certainly again it doesn’t allow for the woman with breast cancer to get her surgery, which is, again, just beginning as we start to see things around return to work, what health systems call return to care.