Patient Selection Takes Priority as Standard of Cares Shift in HR+ and HER2+ Breast Cancer

With the array of CDK4/6 inhibitors available for patients with hormone receptor (HR)–positive breast cancer, treatment optimization according to patient characteristics is crucial, according to Lauren E. Nye, MD, who added that additional treatments are on the horizon for patients with brain metastases.

In an interview with OncLive® following a State of the Science Summit™ (SOSS) on breast cancer, Nye discussed key points that were presented at the meeting, including crucial treatment considerations when using CDK4/6 inhibitors in patients with HR-positive metastatic breast cancer, the ongoing evolution of antibody-drug conjugates (ADCs) for patients with HER2-positive disease, novel surgical techniques to prevent lymphedema, and factors that influence the use or omission of regional nodal irradiation.

“There was also a lot of excitement about the phase 3 D-TORCH trial [CTRI/2021/01/030592], which is [investigating the use of] topical diclofenac [Voltaren] gel to try and prevent capecitabine-induced palmar-plantar erythrodysesthesia,” Nye noted. “The audience was excited about trying to implement that in their clinical practice as a preventive measure.”

Nye, who is the clinical medical director of breast cancer prevention at the University of Kansas Cancer Center in Kansas City, provided additional insights on expanding treatments for patients with advanced breast cancer beyond CDK4/6 inhibitors in another article .

OncLive: Regarding the presentation by your colleague, Jodie Barr, DO, of Lawrence Memorial Hospital in Kansas, what have been some pivotal treatment updates for patients with early-stage breast cancer?

Nye: Dr Barr talked about updates in early-stage breast cancer and emphasized the advent of adjuvant CDK4/6 inhibitors [for patients with] HR-positive breast cancer with higher-risk disease. We currently have abemaciclib [Verzenio], but we’re also waiting for the approval of ribociclib [Kisqali] in this setting. [The use of ribociclib would be] a great opportunity to further reduce risk in patients with high-risk HR-positive breast cancer.

Dr Barr also talked about immunotherapy in early-stage triple-negative breast cancer [TNBC]. There’s a benefit, based on the phase 3 KEYNOTE-522 trial [NCT03036488] data, with neoadjuvant immunotherapy [plus chemotherapy vs placebo/chemotherapy in this patient population]. We’re awaiting further studies to determine which patients with early-stage TNBC need adjuvant immunotherapy. Since there is toxicity [associated] with immunotherapy, we want to make sure the right patients are getting what they need with fewer toxicities.

Based on the presentation by Ryan K. Rader, MD, of the University of Kansas Cancer Center, what developments in the management of HER2-positive breast cancer should your colleagues keep an eye on?

The biggest takeaways from Dr Rader’s presentation [included the discussion of the] ADCs ado-trastuzumab emtansine [Kadcyla], fam-trastuzumab deruxtecan-nxki [Enhertu; T-DXd], and [others] on the horizon. Additionally, the emerging data in HER2-positive brain metastases have been exciting. The effectiveness of T-DXd, as well as tucatinib [Tukysa], in active brain metastases has been promising. Hopefully, more trials will include patients with active brain metastases, so we can better understand which agents will be effective for those patients.

Based on the debate showcased at the SOSS regarding the use of frontline CDK4/6 inhibitors, what should oncologists keep in mind when considering these agents as first-line treatments for patients with HR-positive disease?

In our frontline CDK4/6 inhibitor debate, we talked about the use of CDK4/6 inhibitors in HR-positive metastatic breast cancer. We have 3 options right now: palbociclib [Ibrance], ribociclib, and abemaciclib. All these CDK4/6 inhibitors work by inhibiting progression of the cell cycle to the S phase from the G1 phase. There are differences in selectivity for CDK4/6 between the agents and differences in their chemical structures that may lead to differences in toxicity. Although all the agents have good efficacy regarding progression-free survival, there are some differences [between them regarding] overall survival.

However, what our debate came down to was differences in toxicity and what [agent] we would choose for an individual patient. If a patient has a lot of comorbidities or is young and healthy, we may choose different agents depending on the patient and their overall health. We also talked about which agents, such as abemaciclib, we may consider in a patient with brain metastases, or [which patients may need] an agent to be combined with tamoxifen, where we have some data with ribociclib in premenopausal women. We fleshed out which agents we may use in different case scenarios.

Regarding the presentation Lyndsey J. Kilgore, MD, FACS, of the University of Kansas Medical Center, gave about breast surgery, what should medical oncologists know about future directions for axillary lymph node surgery?

Dr Kilgore focused on the surgical management of the axilla, seeing the future of breast surgery try and back away from axillary lymph node dissection as much as possible, and [identifying] when a targeted axillary dissection would be appropriate. For patients who need to undergo axillary lymph node dissection, there was an emphasis on the risk of breast cancer–related lymphedema and new techniques that are being used to try to prevent lymphedema including immediate lymphatic reconstruction.

What are some key updates in breast radiation oncology, as discussed by Shane R. Stecklein, MD, PhD, of The University of Kansas Cancer Center?

In radiation oncology, we have seen updates in [the management of] low-volume axillary disease. Axillary lymph node dissection may not be necessary, and regional nodal irradiation [RNI] can give equivalent outcomes with less morbidity for some patients. In addition, RNI [has been shown to] provide no benefit to patients with HER2-positive breast cancer and TNBC with clinically N1 disease who converted to N0 disease with neoadjuvant systemic therapy. Therefore, in some instances, we can now consider the omission of RNI for patients who convert to pathologic complete response with neoadjuvant chemotherapy.