Physicians Discuss Modifying Use of CDK4/6 Inhibitors in ER+/HR+ Metastatic Breast Cancer

Reshma L. Mahtani, DO

Chief of Breast Medical Oncology

Miami Cancer Institute

Miami, FL

DISCUSSION QUESTIONS

• Which CDK4/6 inhibitor (CDK4/6i) are you using most often as first-line therapy? ​
• Do the data from the MAINTAIN (NCT02632045) and/or PACE (NCT03147287) studies influence your practice in any way?​

RESHMA MAHTANI, MD: Are you using CDK4/6i in combination with endocrine therapy for most of your patients? Now that we have some survival data with ribociclib [Kisqali] and we have an interim analysis that strongly pointing towards survival data with abemaciclib [Verzenio], has that influenced your use of a particular CDK4/6i?^1,2 And are you continuing CDK4/6i in patients who progress?

JONATHAN TICKU, MD: In the older [or] frail patients, I've still been using palbociclib [Ibrance]; because of the toxicity profile, I find it's more beneficial. In the other patients I've been transitioning to abemaciclib, they can tolerate the toxicity a bit better. I have been continuing to [treat] beyond progression in some patients, [for instance] if there's a bone metastasis [and they] progress, treat them locally with radiation therapy then continue them through. But I haven’t taken…the MAINTAIN study or things like that…into account, particularly.

MAHTANI: It seems like in your practice, it's a particular patient for whom you may consider that approach, but it's not across the board a…thing that you're doing. Was anyone else continuing CDK4/6i beyond progression, routinely before MAINTAIN and PACE? Or were you not, and now you are? How do these datasets inform what you're doing?

JORGE HURTADO, MD: I didn't before. I read the MAINTAIN trial data, and if I [understood] it correctly, a lot of the patients [in the trial] were on palbociclib.³ Only a few patients were on ribociclib, [and 2 patients] on abemaciclib. There are a lot of theories out there that palbociclib is the weakest one. I'm not sure if that's correct, but if I have some patients on palbociclib I might consider switching to ribociclib. But if I had somebody on ribociclib or abemaciclib and they progress, I might not continue the CDK4/6i and think about something else, because I'm afraid I'm going be giving toxicity, [but] I'm not giving much benefit.

MAHTANI: So you're inclined to consider it in a patient who was on palbociclib, because you're thinking you would be switching to a different, perhaps more effective, CDK4/6i. But if they already had abemaciclib or ribociclib, you're thinking there's no point in trying more. Does anyone else agree with that approach or have a different thought?

SUMITHRA VATTIGUNTA, MD: I've had a lot of experience with palbociclib, because that's what we started with and I feel comfortable using it. Like you said, if the patient had a long, disease-free interval and has been on palbociclib for a long time, I am switching those patients to abemaciclib, [but] it's a little difficult with the adverse event profile. I think abemaciclib is, with the diarrhea, not easy initially…. I've had patients who also had renal insufficiency and needed hydration. But if they progress in a short while, I don't do the CDK4/6i because it's not going to work, even if you switch to the new ones. I tend to use more palbociclib. I know there's more data with the ribociclib, especially with the recent overall survival benefit. I've been trying to switch but it's not universal.

MAHTANI: One of the challenges we face in Florida is that our patient population is a bit [less fit]. When you see the drugs in terms of what's best tolerated, we're all used to palbociclib and it seems to be well tolerated, especially in our older patients with fewer drug-drug interactions and things of that sort. I share your experience in that.

_REFERENCES:

_{1. Finn RS. Rugo HS, Dieras VC, et al. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2− ABC): Analyses from PALOMA-2. J Clin Oncol. 2022;40(suppl_17):LBA1003. doi.10.1200/JCO.2022.40.17_suppl.LBA1003}

_{2. Goetz MP, Toi M, Huober J, et al. Interim overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor in patients with HR+, HER2– advanced breast cancer. Ann Oncol. 2022;33(suppl_7):S808-S869. doi:10.1016/annonc/annonc1089}

_{3. Kalinsky K, Acordino MK, Chiuzan C, et al. A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial. J Clin Oncol. 2022;40(suppl_17):LBA1004. doi:10.1200/JCO.2022.40.17_suppl.LBA1004}