Expanding Armamentarium Allows for Tailored Approaches in Breast Cancer, in Especially Older Patients

Martine Extermann, MD, PhD

The widening treatment paradigm for various breast cancer subtypes is yielding improved survival with more tailored strategies, Martine Extermann, MD, PhD, said, adding that de-intensified regimens, such as single-agent trastuzumab (Herceptin) without chemotherapy, could provide older patients with prolonged responses without significant toxicity.

“[Breast cancer] is a disease that is becoming increasingly chronic, and women can live many years with it. They may need treatment for it, but it is no time to be nihilistic about treating [patients with] metastatic breast cancer,” said Extermann, a professor of oncology and medicine at the University of South Florida and program leader in the Senior Adult Oncology Program at Moffitt Cancer Center, in an interview with OncLive® during an Institutional Perspectives in Cancer webinar on breast cancer.

“No matter the patient’s age or condition, we should offer them oncologic treatments. We have many choices that we can tailor to the patients’ goals of care and their health,” Extermann added.

The virtual meeting covered key updates to the paradigms of triple-negative breast cancer (TNBC), hormone receptor (HR)–positive breast cancer, and metastatic HER2-positive breast cancer, as well as explored the optimal treatment intensity for older women with breast cancer.

In the interview, Extermann, who chaired the event, discussed relevant updates in the treatment of patients with breast cancer and individualizing treatment for geriatric patients.

OncLive®: Of all of the recent updates in breast cancer, which ones do you find to be most compelling?

Extermann: Many new updates [have emerged] in breast cancer this year. It is exciting to see [the field] moving [forward]. One of the things that everybody welcomed was the third-line options for patients with HER2-positive breast cancer. We have 2 drugs, [fam-trastuzumab deruxtecan (Enhertu) and tucatinib (Tukysa)], that came to the market and have good efficacy as third-line treatments for patients with HER2-positive breast cancer, including those with brain metastases.

The other thing that was also very exciting to see was that the olaparib [Lynparza] results seem to transfer from the metastatic to the adjuvant setting for subgroups of women with breast cancer.

As a geriatric oncologist, I follow what is happening to improve the care of older women with breast cancer very closely. Just as a reminder, 35% of breast cancer happens beyond the age of 75 years. We need to pay attention to this population of patients. Some interesting developments [emerged] in what we can give and expect with low-toxicity regimens [in geriatric patients]. [We also saw] updates on how helpful radiation may be in these patients. [We also are developing] better ways of selecting patients for treatment with geriatric assessment and intervention so that patients have less adverse effects [AEs] from treatment.

One of the presentations focused on CDK4/6 inhibitors. How have updates with this class of agents, such as palbociclib (Ibrance), added to the treatment of patients with HR-positive breast cancer?

CDK4/6 inhibitors are a very helpful [class] of drugs that we are using in the frontline setting for patients with metastatic [HR-positive] breast cancer. We have 3 [CDK4/6 inhibitors] that we can use: palbociclib, ribociclib [Kisqali], and abemaciclib [Verzenio]. All the studies [with these agents] were updated over the past year, and they seem to confirm that this is a class of drug that has a durable effect. Regarding the improvement in survival, some companies have been trying to [eliminate] the P values. P values are pretty [top of mind], but we must remember that this [equates to] statistical significance, and, clinically, these curves are superimposable.

The consensus [during the IPC meeting] was that CDK4/6 inhibitors are equivalent to each other in effectiveness. The AE profile is slightly different, so [the decision to pick 1 agent over another] depends on [individual] patients. [Safety] is what should guide choosing [a CDK4/6 inhibitor].

Another lecture highlighted recent advances in TNBC. How has the FDA approval of sacituzumab govitecan-hziy (Trodelvy) affected this paradigm, particularly for older patients? Has it changed sequencing?

Sacituzumab govitecan is a very welcome addition to the chemotherapy [options] and novel treatments we can give for TNBC. An interesting aspect of the [pivotal trial with sacituzumab govitecan] is that there seems to be some central nervous system [CNS] activity. For women with CNS disease, [utilizing sacituzumab govitecan] might be interesting.

The exact [sequencing] of sacituzumab govitecan [among] all the choices we have is still to be determined. In metastatic breast cancer, when we have the choice between a lot of effective drugs, the choice should be based on the AE profile and patient convenience. For instance, if I have someone who lives far away, I might give them a [drug that is given] monthly.

The older [patients’ treatments] seem to be dictated more by mechanism of action and what they [developed] resistance to, as well as underlying comorbidities they may have. I like the fact that sacituzumab govitecan [offers] a bit of a different approach than systemic chemotherapies. I have [administered sacituzumab govitecan] successfully to some patients.

What data have informed how to tailor treatment intensity to older patients with breast cancer?

The first takeaway was about radiation therapy. We had a couple of studies a few years ago, including the PRIME-II and CALGB 9343 studies, that showed that we can forego radiation for a subgroup of women with low-risk estrogen receptor [ER]–positive breast cancer. Those patients may then have a slightly higher risk of relapse, but no difference in survival. A lot of patients choose that option.

The update of the PRIME-II trial gave us some warning that if the patient has low ER status, the risk of local relapse is as high as 18.8% at 10 years. If we’re treating a woman with this subtype of disease, we might still want to give radiation therapy.

The second update answered a question that we ask ourselves with frail patients or individuals who are reluctant to have chemotherapy and are HER2 positive. The question was: Is giving trastuzumab alone sufficient in comparison with chemotherapy plus trastuzumab? The Japanese [RESPECT] study [NCT01104935] was published this past year showing that [trastuzumab and trastuzumab plus chemotherapy] don’t have quite equivalent efficacy. We lose about 3% of overall survival [OS] at 3 years with trastuzumab alone. [However, patients who received trastuzumab alone] had a better quality of life [QOL] and safety profile.

We at least now have some data [there]. The survival was very high in both groups; 92% in the trastuzumab alone group and 95% in the trastuzumab plus chemotherapy group. This is a useful piece of data to offer to our older patients who may be very worried about chemotherapy. If they are willing to get a trade-off [of 3% OS benefit], they can choose [trastuzumab alone].

The RxPONDER study [NCT01272037] was another very helpful trial because when we [detect a] positive node, we have always asked whether we should give chemotherapy. The results of RxPONDER study tell us that in postmenopausal women, if the Oncotype [DX recurrence score] is 25 or lower, they do not benefit from chemotherapy. That is good news for our patients.

The meeting also discussed updates in HER2-positive breast cancer. How have the findings from the phase 3 FeDeriCa (NCT03493854) and the phase 2 PHranceSCa (NCT03674112) trials confirmed the utility of the subcutaneous formulation of trastuzumab, pertuzumab (Perjeta), and hyaluronidase-zzxf (Phesgo) plus intravenous chemotherapy in patients with early and metastatic disease?

[The subcutaneous formulation offers] a very helpful way to deliver [trastuzumab and pertuzumab]. Subcutaneous [administration] means less time in an [infusion center] chair [for the patient].

These are typically well-tolerated drugs in terms of acute reactions. The diarrhea problem is the same [with the intravenous vs subcutaneous formulations].

Ultimately, now we have options, and we have adopted that [subcutaneous formulation] for a lot of our patients.

Is there anything else you’d like to highlight?

Beyond breast cancer alone, and for all older patients with cancer, there are multiple randomized studies that have been published in the past few years showing very consistently, that if we do a simple geriatric screening—ideally with some geriatric management behind it—we can modify decisions for 1 in 4 patients.

We decrease toxicity, but survival remains unaffected. Geriatric assessment should be part of the treatment for every older patient with cancer. It is a level 1 evidence-based approach for patients with cancer.