CDK4/6 Inhibitors for HR+ Metastatic Breast Cancer

Transcript:Carlos L. Arteaga, MD: We should also be reminded that for some patients, these CDK4 inhibitors present a bit of an inconvenience. Not all of them need this drug, necessarily. And for those of us who practice in rural communities, having a patient come every month for a blood count can sometimes be complicated. We’re finding out that, for example, the PALA study, which is an adjuvant study…

Adam M. Brufsky, MD, PhD: Yes, it’s a good trial.

Carlos L. Arteaga, MD: It’s a great study, I agree, but some patients are turning it down because they’re not being treated for metastatic disease. This is for adjuvant disease. So, they’re thinking twice about whether or not they want to commit to the visits and blood testing that the trial requires.

Adam M. Brufsky, MD, PhD: I think you’ve hit on something here that’s important. The patients aren’t paying a clinical price, but they’re paying a financial price. I think that’s really what this comes down to. Ribociclib or palbociclib, maybe abemaciclib—if these drugs were $100 a month, we wouldn’t be having this discussion. They’re $10,000 a month, roughly, and so the issue is that if there’s a survival benefit, Debu, will we have to use these drugs in everybody regardless?

Debu Tripathy, MD: Well, we’re using them, I must say, in a vast majority of our patients. Many times, I get asked, “Is there a subpopulation that you think does not need CDK4/6 inhibition upfront?” and I’d like to know if anyone else on the panel feels that way. But I don’t know of any factors other than convenience and cost that would identify such patients.

Adam M. Brufsky, MD, PhD: Kim, do you give it to everybody?

Kimberly L. Blackwell, MD: Pretty much. People argue, “Oh, it’s only for those with isolated bone metastases or with a long disease-free interval since adjuvant therapy.” But, if you look at the subgroup analysis on the studies where we have the most mature data, PALOMA-2 and PALOMA-3, the women facing bone-only ER-positive breast cancer derive just as much benefit as the patients facing heavy-burden visceral disease. Just from a pure efficacy standpoint, I’ve not been able to define a subgroup of patients.

Now, Carlos raised a good point: the patient who doesn’t want to come in every 2 weeks, at least for the first 2 months, and every month thereafter. I guess my experience has been that when a woman is diagnosed with a recurrence, she likes to come to my office every 2 weeks for the first 2 months. We have a lot to discuss. She’s in the midst of a crisis. We’re usually trying to get her bone health agent approved. There’s just a lot going on, so I don’t think the actual visit has created much more of an inconvenience than what we would see in the old days.

José Baselga, MD, PhD: These are patients that classically would have received chemotherapy much earlier, right? There is no comparison. Their quality of life is…

Adam M. Brufsky, MD, PhD: That’s a really good point. That’s a point we really need to emphasize. I think that most of us on this panel, and we should ask everybody, are believers in the whole visceral crisis concept of chemotherapy. That is, you don’t treat a patient with chemotherapy in this setting unless they really are a month or 2 away from having maybe liver failure. Do people believe that? Denise, are you a believer in visceral crisis for chemotherapy?

Denise A. Yardley, MD: Yes. I think that there is a certain group of patients where chemotherapy may be a more appropriate choice to rescue those patients.

Adam M. Brufsky, MD, PhD: Right. But the issue is when someone comes in with a couple of liver metastases or is asymptomatic. Maybe they have a couple of 1 cm, 2 cm, or 3 cm liver metastases or a few lung metastases; maybe they had a pleural effusion that has been drained or have a PleurX system in. Normally, in the past, we would have given chemotherapy, but now, would most of us here do a CDK4 inhibitor and hormone therapy?

Kimberly L. Blackwell, MD: My thinking about that was heavily influenced. There was a preoperative study presented at the San Antonio Breast Cancer Symposium in 2016, and they compared the use of an AI alone versus a CDK inhibitor—it was abemaciclib. And what they saw was close to 90% reduction in Ki-67 at day 14 biopsies. That’s as good as what we see with chemotherapy, certainly. The thing that I like about patients who are symptomatic from their disease is that we know these CDK inhibitors kick in, whereas the AIs can take a matter of weeks.

So, again, I think that’s a potential benefit for a symptomatic patient—adding these drugs. And I agree with José, the price of chemotherapy is a horrible one, not only for the patient but also the cost. Anything that kicks that can down the road by a matter of months is worth it. I don’t necessarily need to see a survival benefit with these drugs.

Transcript Edited for Clarity