Insights From: Hope S. Rugo, MD, UCSF Helen Diller Family Comprehensive Cancer Center; Sara Hurvitz, MD, UCLA Jonsson Comprehensive Cancer Center
Sara Hurvitz, MD: The PALOMA-2 and MONALEESA-2 clinical trials are actually fairly similarly designed, and if you look at the baseline patient characteristics for these 2 clinical trials, they’re actually quite similar with similar numbers of patients who had visceral metastases. If you look at patients’ number of prior lines of therapy, number of sites of disease, it’s hard to really see a significant difference between these 2 clinical trials. So, when I’m looking at an individual patient and deciding whether or not to use palbociclib or ribociclib, I’ll take into consideration a couple of factors: Does this patient have a problem or preexisting issue with cardiac arrhythmia or QTc prolongation? Is she on medications that might affect her QTc interval? And if that’s the case, then I would be less inclined to use ribociclib. However, that being said, the 2 drugs are actually quite similar. And if you look at the efficacy outcomes and the toxicity profile of the 2 drugs, the delta or the difference between PFS in the study arm and the control arm for each of the studies are quite similar. So, I don’t see an advantage, from a patient perspective, of being on one versus the other.
I do think one thing that we oncologists don’t consider often enough is patient cost and its impact on the patient in terms of economic and health resources. So, if a patient has their copay assistance or better availability of 1 drug over the other in the clinic setting, I think that’s a very relevant and important factor for us to take into consideration. In terms of the second- and third-line setting, right now the only drug we have approved in patients who have been previously treated with up to a line of chemotherapy or endocrine therapy is palbociclib in combination with fulvestrant, based on the PALOMA-3 study. So, right now, if a patient has progressed on single-agent AI, for example, or first-line capecitabine, the drug that is FDA approved in this indication is palbociclib/fulvestrant.
That said, abemaciclib has been tested in combination with fulvestrant and has been shown to significantly prolong progression-free survival for patients. So, if abemaciclib is approved in the second-line setting, then we’ll have a second option for patients. How would I choose between abemaciclib and palbociclib? Well, I think abemaciclib is easier to remember in terms of how to take it. It’s a twice-daily dosing and there are no breaks. Patients don’t need to remember to come into clinic and have their blood count checked before starting their next cycle. And so, there is a little bit of patient ease factoring into that decision. On the other hand, abemaciclib has more diarrhea associated with it. So, if I had a patient with irritable bowel syndrome or other gastrointestinal problems, I’d probably be more inclined to prescribe palbociclib for these patients.
Another option that patients have in the frontline setting is, of course, single-agent fulvestrant given at a dose of 500 mg day 1, day 15, and then monthly thereafter. Fulvestrant has been studied in a phase III clinical trial head-to-head against anastrozole in hormone receptor-positive postmenopausal women with metastatic breast cancer that has never been treated with endocrine therapy. In this study, the use of fulvestrant improved progression-free survival significantly compared to anastrozole. But when you look at the subgroup analysis, what you can see is that those patients with bone-only disease really benefit from the fulvestrant compared to anastrozole, to the point that the progression-free survival was over 23 months with fulvestrant, similar to the results that we’ve seen with CDK4/6 inhibitors in this setting.
On the other hand, patients who had visceral metastases, there really wasn’t a benefit from the use of fulvestrant compared to anastrozole. Both performed similarly, and neither were in the range of 23 months. So, in a patient who has visceral disease, one might take this into consideration as data to discourage one from using fulvestrant as a single agent in the frontline setting and encourage you to look more at the CDK4/6 inhibitors. From a personal perspective, I really think CDK4/6 inhibition should be offered to patients in the frontline setting. Though the fulvestrant data are impressive in the fact that patients don’t need to remember to take a pill, they’re coming in for their injections would certainly improve compliance for some patients where compliance may be problematic.