Dr Basho on Treatment Considerations With ADCs in Breast Cancer

Reva K Basho, MD, senior director, the Women's Cancer Program, the Ellison Institute, Providence Specialty Medical Group, discusses the use of antibody-drug conjugates (ADCs) across the spectrum of breast cancer subtypes 

at the 2023 Bridging the Gaps in Breast Cancer meeting

Basho says that oncologists are fortunate to be practicing in a time when numerous ADCs are entering the breast cancer armamentarium and improving patient outcomes. However, with the growing number of available agents, particularly those with similar payloads, it has become important to contemplate the sequencing of these treatments, she states. This becomes especially critical as these agents advance into earlier lines of therapy, encompassing curative and first-line metastatic disease, Basho explains. A key issue that has also arisen is how to navigate the treatment of patients transitioning from ADCs, she notes.

Delving into the underlying mechanisms of resistance is pivotal—whether it occurs at the antibody or payload level—and gaining a nuanced understanding is essential to effectively tailor the selection of agents for individual patients, Basho continues. The applicability of this inquiry extends across the diverse subtypes of breast cancer. Notably, ADCs are now being employed in the metastatic setting for patients with HER2-positive, triple-negative, hormone receptor–positive, and HER2-low disease, rendering this question relevant for a wide spectrum of patients with breast cancer, she emphasizes. Ideally, the implementation of ADCs as a method for chemotherapy delivery holds promise for accessing more potent payloads and adopting a targeted approach through antibody targeting, she says.

In considering the broader landscape, questions about sequencing become pertinent, and this extends to a broad population of patients, Basho expands. Through pan-tumor studies, insights have been gained on understanding how to navigate the complexities of ADC treatments that may potentially benefit a wide array of individuals, Basho concludes.

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Reva K Basho, MD, discusses the use of antibody-drug conjugates across the spectrum of breast cancer subtypes at the 2023 Bridging the Gaps in Breast Cancer meeting.


Reva K. Basho, MD, assistant professor of medicine, co-director, Women’s Cancer Program, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, discusses the emergence of bispecific antibodies in HER2-positive breast cancer.

Although several agents are emerging for use in HER2-positive breast cancer, anticipated data regarding bispecific antibodies are of particular interest, Basho says. Bispecific antibodies have the potential to dually target HER2 and another target, such as an immune target, in turn, eliciting a synergistic effect.

Additionally, some bispecific antibodies, such as zanidatamab, dually target HER2, Basho says. Zanidatamab targets HER2 at the pertuzumab (Perjeta) binding site, as well as the trastuzumab (Herceptin) binding site, Basho explains. Notably, dual HER2-targeting bispecific antibodies could potentially replace the combination of trastuzumab and pertuzumab as a frontline strategy in metastatic HER2-positive breast cancer, where the doublet plus chemotherapy remains the standard frontline therapy, Basho concludes.

Reva K. Basho, MD, discusses the emergence of bispecific antibodies in HER2-positive breast cancer.  



Dr. Basho on the Emergence of Bispecific Antibodies in HER2+ Breast Cancer 

Reva K. Basho, MD, assistant professor of medicine, co-director, Women’s Cancer Program, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, discusses the evolution of therapeutic sequencing in HER2-positive breast cancer.

Based on findings from the phase 3 CLEOPATRA trial (NCT00567190), the combination of docetaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta) has remained the frontline standard of care for patients with HER2-positive breast cancer, Bashoexplains. In the second-line setting, ado-trastuzumab emtansine (T-DM1; Kadcyla) was the standard of care option, Basho adds. Beyond this, physicians were left with the choice of how to treat patients that typically included chemotherapy in combination with HER2-directed therapy, Basho adds. 

Novel FDA-approved agents have expanded the paradigm of HER2-positive breast cancer treatment, Basho says. For example, fam-trastuzumab deruxtecan-nxki (Enhertu) and tucatinib (Tukysa) have become established regimens in the third- and fourth-line settings for this patient population, Basho explains. Additional agents are emerging for use in HER2-positive breast cancer that could further shift sequencing, Basho concludes.

Reva K. Basho, MD, discusses the evolution of therapeutic sequencing in HER2-positive breast cancer. 

Dr. Basho on the Evolution of Therapeutic Sequencing in HER2+ Breast Cancer 

Reva K. Basho, MD, assistant professor of medicine, co-director, Women’s Cancer Program, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, discusses the integration of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive breast cancer. 

Following its FDA approval in December 2019, trastuzumab deruxtecan has become a standard third- or fourth-line therapy for patients with HER2-positive breast cancer, Basho says. When to sequence the agent is largely dependent on patient and physician preferences, Basho adds. 

However, toxicity remains a concern with trastuzumab deruxtecan, particularly with regard to the risk of fatal interstitial lung disease (ILD), Basho explains. Other therapies that are available for later-line use in HER2-positive breast cancer are generally well tolerated with limited alopecia, Basho says. As such, safety needs to be considered when selecting trastuzumab deruxtecan for a patient, Basho concludes. 

Reva K. Basho, MD, discusses the integration of fam-trastuzumab deruxtecan-nxki in HER2-positive breast cancer.  



Reva K. Basho, MD

Articles

Dr Basho on Treatment Considerations With ADCs in Breast Cancer

Dr. Basho on the Emergence of Bispecific Antibodies in HER2+ Breast Cancer

Dr. Basho on the Evolution of Therapeutic Sequencing in HER2+ Breast Cancer

Dr. Basho on the Integration of Trastuzumab Deruxtecan in HER2+ Breast Cancer