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Advances in Breast Cancer Treatment Reshape Treatment Paradigms in 2022

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The increasing role of antibody-drug conjugates have led to questions of sequencing for patients with HER2-positive breast cancer, whereas new data for first-generation PD-L1 inhibitors, such as pembrolizumab have shaken up the treatment paradigm for others.

Therapies old and new have improved outcomes for many subtypes of breast cancer in 2022, according to Tiffany A. Traina, MD. The increasing role of antibody-drug conjugates (ADCs) have led to questions of sequencing for patients with HER2-positive disease, whereas new data for first-generation PD-L1 inhibitors, such as pembrolizumab (Keytruda) have shaken up the treatment paradigm for others.

Traina served as co-chair of the 40th Annual CFS® where she also served as moderator of the breast cancer session and delivered a presentation titled: “Early-Stage Triple-Negative Breast Cancer.”

“It’s an exciting time to be in the breast cancer space,” Traina said. “[The CFS® presentations] were each approximately 15 minutes and that was inadequate time to cover all that’s new and exciting [in the field]. The key takeaway is that there’s tremendous hope for our patients with advanced disease and early disease and we’re curing more women with breast cancer as a result of these great novel therapies.”

In an interview with OncLive®, Trainia, section head of the Triple Negative Breast Cancer Clinical Research Program at Memorial Sloan Kettering Cancer Center, discussed how trials including HER2CLIMB (NCT02614794) and CLEOPATRA (NCT00567190) have shifted the treatment paradigm and provided additional options for patients.

What were some of the key highlights from the breast cancer assessments held at CFS®?

The breast cancer sessions [at] CFS® were fantastic. The highlights for me were hearing about the new ADCs and their role not only in HER2-positive breast cancer, but also in HER2-low and triple-negative breast cancer [TNBC]. [It] was exciting to go over the new data from this past year.

Another exciting lecture was around novel pathways and mutations in hormone receptor–positive advanced breast cancer that Sarat Chandarlapaty, MD, PhD, shared. It was encouraging to hear that there may be new targeted therapies on the horizon to help our patients with endocrine-resistant or refractory, advanced disease.

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What ADCs could potentially affect the breast cancer treatment paradigm?

There are several different ADCs out that are available for either HER2-low breast cancer, TNBC, or hormone receptor–positive breast cancer that targets TROP2, but there are several on the horizon.

We’ve seen data for an ADC against HER3 with the same deruxtecan payload. We’ve also recently seen data [for] sacituzumab govitecan-hziy [Trodelvy] in hormone receptor–positive breast cancer from the TROPiCS-02 study [NCT03901339]. We have ADCs that target Nectin-4 and that is a study that has recently completed, we haven’t yet seen those data. There are several novel combinations of new targets and different payloads to differentiate these different ADCs in development.

What are some of the factors in determining sequencing for HER2-positive breast cancer?

[Shanu Modi, MD,]’s presentation around what is new in HER2-positive breast cancer was fantastic. One of the challenges when there are so many active drugs is trying to understand how to sequence these. We know that in the first-line setting the CLEOPATRA regimen [of dual targeting with pertuzumab (Perjeta) and trastuzumab (Hercepin) plus chemotherapy] remains standard of care, but beyond that Dr Modi proposed an algorithm of how to sequence these agents. In the second-line setting for patients who have central nervous system [CNS] disease, there was a preference for looking at the HER2CLIMB regimen as an option with the tyrosine kinase inhibitor tucatinib [Tukysa] with trastuzumab and capecitabine.

Although we have some data for trastuzumab deruxtecan-nxki [Enhertu] [showing] CNS penetration and benefit in that situation [where a patient has] CNS metastases, the proposed algorithm had the ADC trastuzumab deruxtecan coming after the HER2CLIMB regimen. Otherwise, trastuzumab deruxtecan in the second-line setting has been well supported by the DESTINY-Breast03 study [NCT03529110] and so that held that second-line space.

Thereafter, we again are faced with a lot of different great options that are active and whichever regimen you haven’t used in the second- line setting remains an option in the third-line setting. Plus, we’re seeing then [ado-trastuzumab emtansine (T-DM1; Kadcyla)] bumped down the line a little bit as an option subsequent to that.

Clinical trials are always a great option [for patients as well].

What were the key points from your presentation on treating early-stage TNBC?

We talked a bit today about using adjuvant olaparib [Lynparza] in patients who have germline BRCA mutations. We reinforced the use of capecitabine in the adjuvant setting for patients who are germline BRCA wild-type and have residual disease. We talked as well about clinical trials that are trying to answer some of the questions about appropriate duration of therapy [such as] where we can potentially escalate and de-escalate therapy.

The paradigm for managing early-stage triple negative breast cancer has changed over the past year and a half as a result of KEYNOTE-522 [NCT03036488]. Immunotherapy with pembrolizumab added to taxane/platinum, anthracycline, [and] cyclophosphamide in the neoadjuvant setting has now become standard of care. Using neoadjuvant therapy in that way helps us to estimate risk and prognosis in patients that have residual disease after optimal preoperative therapy.


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