Bhuvaneswari Ramaswamy, MD, and colleagues highlight treatment for patients with HR-positive breast cancer, discuss the role of pembrolizumab plus chemotherapy in early-stage triple-negative breast cancer, and expand on unmet needs for patients with metastatic HER2-positive breast cancer.
Real-world data indicate an overall survival (OS) benefit with the use of palbociclib (Ibrance) plus an aromatase inhibitor (AI) in patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer despite failing to show such benefit compared with an AI alone in this population in the pivotal, phase 3 PALOMA-2 trial (NCT01740427), according to Bhuvaneswari Ramaswamy, MD.1,2
During an OncLive® State of the Science Summit™ on breast cancer, Ramaswamy and colleagues highlighted treatment for patients with HR-positive breast cancer, discussed the role of pembrolizumab (Keytruda) plus chemotherapy in early-stage triple-negative breast cancer (TNBC), and expanded on unmet needs for patients with metastatic HER2-positive breast cancer. Ramaswamy, who chaired the event, is an assistant professor at The Ohio State University (OSU) Medical Center, a breast medical oncologist in the Translational Therapeutics Program, section chief of Breast Medical Oncology, and director of the Medical Oncology Fellowship Program in Breast Cancer, at The Ohio State College of Medicine, OSU Cancer Center (OSUCC)–James in Columbus.
Ramaswamy was joined by her colleagues:
Below, Ramaswamy, Johnson, Quiroga, Williams, and Gatti-Mays summarize the main messages from their presentations.
Ramaswamy: We talked about different therapies [in HR-positive breast cancer]. These are not just new therapies. They are targeted and biologically relevant therapies that are improving outcomes. [We must] also understand real-world data, because we do have some [prospective data] showing improvement in OS with CDK4/6 inhibitors in the metastatic setting, and some [data showing a lack of OS improvement]. However, we still use a lot of palbociclib. There are still questions with palbociclib [after prospective data did not demonstrate an OS benefit], but there are real-world data showing that they are also seeing OS improvement. Is this just a restrictive approach? Is there a different biology or different targets that are affecting that [OS] outcome in a randomized study? It is important to ask these questions because in some patients, we are still using palbociclib. We shouldn't abandon palbociclib, because at this point, we still see that real-world data supporting its use.
Are there some patients where we could avoid giving a CDK4/6 inhibitor initially and go with anti-estrogen approaches? You want to have treatment options open. The more [treatments] you throw at patients, the more the cancer cells are going to become resistant. You use [a treatment] when you need it.
Williams: HER2-positive breast cancer occurs in [approximately] 20% of women diagnosed with breast cancer. The majority of these women will initially be diagnosed with early-stage HER2-positive breast cancer. Unfortunately, a percentage of those [women] will develop metastatic breast cancer, and most [of these] women will die from their breast cancer. Therefore, we continue to develop new therapies to improve outcomes for women with metastatic HER2-positive breast cancer.
We've come a long way in the treatment of [patients with] HER2-positive breast cancer. We've had several agents approved within the past 2 to 3 years. Patients with metastatic HER2-positive breast cancer continue to live longer. We are continuing to investigate new and novel therapies in order to continue to improve outcomes in patients with HER2-positive breast cancer.
Gatti-Mays: I briefly reviewed [the phase 3] KEYNOTE-522 trial [NCT03036488], [which led to pembrolizumab plus chemotherapy becoming] the new standard of care for our patients with TNBC in the early-stage setting. The clinical outcomes, whether it was pathologic complete response [pCR] or event-free survival [EFS], were superior with the addition of pembrolizumab to chemotherapy in patients, irrespective of their PD-L1 status. We reviewed that for this neoadjuvant indication for immunotherapy in TNBC, there is no need to check PD-L1 status prior to initiating therapy.
We [also] reviewed EFS [data from KEYNOTE-522] at 3 years. [Regardless of] whether patients had a pCR, those patients who received pembrolizumab plus chemotherapy had superior EFS. I try to ensure that we get pembrolizumab to as many patients who are eligible for the regimen as possible.
[Subsequently] we reviewed the indication [for pembrolizumab plus chemotherapy in early-stage TNBC]. Generally, the indication is for patients who have a 2.1 cm tumor or greater, meaning a T2 lesion, or are node positive. However, in some patients where the tumors are approximately 2 cm, I’ll discuss that there may be additional benefit from the KEYNOTE-522 regimen, and we’ll discuss the pros and cons of proceeding with that regimen.
Johnson: Part of the rationale [for discussing this topic] is to look at the justification for why we treat people the way we do. Just like within any condition, sometimes we get stuck in the historic data while new treatments are emerging. We want to make sure we're reevaluating why we're treating patients a certain way and looking at the evidence behind it.
The biggest unmet need is looking at those who have a cardiac history leading into their diagnosis. All these patients are excluded from trials. We don't know what's safe in terms of anti-HER2 therapy at given [left ventricular ejection fraction (LVEF)] cutoffs. Does an LVEF of 40% mean that we can't give a de-escalated regimen, whether it's an oral TKI, trastuzumab [Herceptin] alone, or pertuzumab [Perjeta] alone? That's something that has yet to be investigated on a prospective level. It will be interesting to see whether we can give these patients [with a cardiac history] the same benefit that we give others, but in a safe manner.
Quiroga: HER2 low is something that has been studied for a while now, but [there has been an] increased interest because there's now a clinical indication for using [HER2-low status] to offer patients new treatment options. It used to be very binary in how we would define HER2 status: you were either positive or negative. However, now we're finding that some of the patients who were previously defined as HER2-negative would fall into the HER2-low category. That [population] makes up approximately 50% of patients who are diagnosed with breast cancer.
What's important is that we recognize that HER2-low status is very prevalent, and we need to continue to ask [if] our patients’ diseases are changing over time. If so, do we need to get more updated information in the form of biopsies or second opinions on previously obtained biologic samples? What additional information can we get as the cancer evolves? We know [cancer evolves], and we [need to know] all available therapies for each of our patients.