DR HURVITZ: This was the Phase III study that was the follow-up to the PALOMA-1 Phase II clinical trial that led to the accelerated approval of palbociclib in the first-line setting for ER-positive, HER2-negative metastatic breast cancer. There were about 660 patients enrolled in this clinical trial. Patients were randomized to placebo plus letrozole versus palbo plus letrozole.

Again, this is the Phase III trial that had a placebo control as part of the design, which is in contrast to the Phase I data that Rich Finn published. And they confirmed the results of PALOMA-1 and showed that there was a 10-month improvement in progression-free survival with the use of palbociclib in the first-line setting. So about 14 months, 14½ months, for the placebo arm versus over 24.5 or 24.8 months for patients receiving palbociclib. So that really kind of confirms the incremental benefit that was seen in the Phase I study. It also confirms the findings of the PALOMA-3 study, which were in the second- and third-line setting and showing really, even if you look by different subsets and subgroups, that the benefit is seen across all subtypes. Objective responses were better.

And, of course, the main side effect and toxicity of this drug is neutropenia. So most of the Grade 3/4 side effects or adverse events were related to neutropenia, which can be managed quite easily by holding the drug and dose reductions. But it is something that is very common. Over 60% of patients will have Grade 3/4 neutropenia with this drug. But I think that 24.8 months of PFS is one of the longest PFSs reported in the first-line ER-positive metastatic setting. So it’s really nice to see the field move forward in such a large jump.

I’m really excited to see the FALCON data, which may have similar results with single-agent fulvestrant versus first-line AI. There was a press release at the end of May that the results — this is a Phase III study that’s confirming the Phase II FIRST study, which was presented by Robertson, which looked at fulvestrant in the first-line setting versus anastrozole. And fulvestrant had a better time to progression, on the order of 23 months as a single agent compared to the first-line AI. So the FALCON study is the Phase III study that was aimed to confirm that. And the press release indicated they did meet that endpoint.

DR LOVE: Can you describe a case right now where you would use hormonal therapy as first-line therapy of metastatic disease without palbo?

DR HURVITZ: I suppose if I had —

DR LOVE: I’ll take that as a “no.”

DR HURVITZ: Yes.

DR LOVE: I mean, what I’ve heard is, sometimes people go, “You have an older patient and they’ve got very indolent disease and it’s not very aggressive. There’s a long disease-free survival.”

DR HURVITZ: Right.

DR LOVE: I guess.

DR HURVITZ: Yes, or a significant infection. I saw a patient yesterday who’s got chronic aspergillosis and probably would not do well with dealing with the neutropenia. And because we can use it in the second- and third-line setting, that particular patient. But it’s few and far between that I would avoid using palbo.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers