Breast cancer treatment advances reshape treatment paradigms in 2022

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

Old and new therapies have improved outcomes for many breast cancer subtypes in 2022, according to Tiffany A. Traina, MD. The growing role of antibody-drug conjugates (ADCs) has led to sequencing questions for patients with HER2-positive disease, while 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 THAT’S IT® where she also moderated the breast cancer session and gave 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 about 15 minutes long and it wasn’t time to cover everything new and exciting [in the field]. The bottom line is that there is tremendous hope for our patients with advanced and early disease and that we are curing more women with breast cancer with these wonderful new therapies.

In an interview with Live®Trainia, Section Head of the Triple Negative Breast Cancer Clinical Research Program at Memorial Sloan Kettering Cancer Center, explained how trials including HER2CLIMB (NCT02614794) and CLEOPATRA (NCT00567190) have changed the treatment paradigm and provided additional options to patients.

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

Breast cancer sessions [at] THAT’S IT® 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 review new data from the past year.

Another exciting talk focused on new pathways and mutations in advanced hormone receptor positive 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 advanced endocrine resistant or refractory disease.

Which ADCs could potentially affect the breast cancer treatment paradigm?

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

We saw data for an ADC against HER3 with the same deruxtecan payload. We have 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 it’s a study that just ended, we haven’t seen that data yet. There are several new combinations of new targets and different payloads to differentiate these different ADCs in development.

What are some of the factors that determine the sequencing of HER2-positive breast cancer?

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

Although we have some data for trastuzumab deruxtecan-nxki [Enhertu] [showing] CNS penetration and advantage in this 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 was well supported by the DESTINY-Breast03 study [NCT03529110] and so it held that second line space.

Afterwards, we are again faced with many different interesting options that are active and the plan that you did not use under the second line remains an option under the third line. Moreover, we then see [ado-trastuzumab emtansine (T-DM1; Kadcyla)] shuffled the line a bit as an option following this.

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

What were the key points in your presentation on treating TNBC at an early stage?

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

The paradigm for the management of 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 plus taxane/platinum, anthracycline, [and] cyclophosphamide in the neoadjuvant setting has now become the standard of care. Using neoadjuvant therapy in this way helps us estimate risk and prognosis in patients who have residual disease after optimal preoperative therapy.

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