Dr Tiwari on the Current Treatment Paradigms for HER2-Positive and HER2-Low Breast Cancers

Shruti Tiwari, MD, medical oncologist, Virginia Cancer Specialists, discusses how 

The treatment paradigm for HER2-low breast cancer has evolved significantly in recent years, marking a transformative period in oncology, Tiwari begins. One of the most exciting developments in this field is the introduction of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), a drug that has demonstrated impressive efficacy in treating HER2-low cancers, Tiwari says. This advancement is particularly noteworthy as it has shown positive results in both estrogen receptor (ER)-positive/HER2-low and ER-negative/HER2-low breast cancers, broadening the scope of effective treatments available for these patient groups, she reports.

For triple-negative breast cancer (TNBC), the availability of a non-chemotherapy option, such as T-DXd, following initial chemotherapy is a significant breakthrough, according to Tiwari. TNBC is difficult to treat, and T-DXD, a targeted, well-tolerated drug, is a substantial improvement over traditional therapies, she elucidates. This drug provides a new line of defense and enhances the quality of life for patients who have already undergone rigorous chemotherapy treatments, Tiwari adds.

Moreover, T-DXd is a valuable addition to the treatment paradigm for ER-positive, HER2-positive breast cancer, Tiwari notes. Transitioning from one chemotherapy line to another can be particularly challenging for these patients, Tiwari explains. This agent is a manageable treatment option that can also effectively target HER2-low cancers without the harsh adverse effects typically associated with chemotherapy, she continues. Another significant addition to the ER-positive, HER2-negative/HER2-low breast cancer treatment armamentarium is sacituzumab govitecan-hziy (Trodelvy), Tiwari explains. These drugs provide oncologists with more tools to combat HER2-low breast cancers, making treatment plans more flexible and personalized, Tiwari emphasizes.

With multiple effective therapies available, it is crucial to establish the best order of administration to maximize patient outcomes, Tiwari says. This consideration involves understanding the unique needs of each patient and the specific characteristics of their cancer to tailor the most effective treatment strategy, she says.

Overall, the availability of T-DXd and sacituzumab govitecan represents a significant leap forward, providing targeted, effective, and well-tolerated treatment alternatives for patients with HER2-positive and HER2-low breast cancer, Tiwari concludes.

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Shruti Tiwari, MD, discusses how the treatment paradigms for HER2-positive and HER2-low breast cancer has evolved in recent years.

Shruti Tiwari, MD, discusses ongoing efforts to address unmet needs through research in HER2-positive and HER2-low breast cancer.

Dr. Tiwari on Ongoing Research in HER2+/HER2-Low Breast Cancer

Shruti Tiwari, MD, medical oncologist, Virginia Cancer Specialists, discusses efforts to address unmet needs and unanswered questions through ongoing research in HER2-positive and HER2-low breast cancer.

Efforts to develop novel agents and more effective treatment regimens within the landscape of HER2-positive and HER2-low breast cancer are constantly evolving, Tiwari begins. Clinical trials play a pivotal role in this dynamic paradigm, with a myriad of new trials and innovative therapies that have the potential to transform disease management in this space, she emphasizes.

Researchers at Virginia Cancer Specialists are actively engaged in 2 clinical trials focused on HER2-low cancers and antibody-drug conjugates (ADCs), Tiwari introduces. One trial is evaluating BNT323/DB-1303, a novel HER2-directed ADC with a TROP1/2 payload, she states. Data previously reported from a first-in-human, multicenter phase 1/2 study (NCT05150691) showed that DB-1303 was well tolerated and produced preliminary antitumor activity in heavily pretreated patients with advanced/metastatic solid tumors, particularly those with HER2-positive breast cancer and brain metastasis as well as in HER2-low disease. This agent is comparable to prior ADCs, but is notable for its tolerability and reduced incidence of alopecia compared to previous ADCs, Tiwari adds.

Despite the successes of current treatments, challenges remain, particularly in terms of treatment durability and tolerability, Tiwari continues. For patients experiencing disease progression after receiving highly effective ADCs such as fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd), there is a critical need for alternative therapies, she explains. Accordingly, a second trial at Virginia Cancer Specialists is exploring the use of a novel immune-stimulating ADC to combat disease progression following treatment with T-DXd, Tiwari details. These clinical trials aim to provide new therapeutic approaches that can address treatment gaps and overcome resistance.

The significance of these trials is reflected in the willingness of patients to travel to Virginia where the trials are being run, seeking access to cutting-edge therapies that are not widely available, Tiwari notes. By participating in these trials, researchers can advance care and provide patients with more effective and better-tolerated treatment options, Tiwari concludes.

Shruti Tiwari, MD, discusses efforts to address unmet needs through ongoing research in HER2-positive and HER2-low breast cancer.

Dr Tiwari on Optimal Treatment Sequencing in HER2+ Breast Cancer

Shruti Tiwari, MD, medical oncologist, Virginia Cancer Specialists, 

 within the realm of HER2-positive breast cancer, highlighting how to treat these patients when they present with central nervous system (CNS) involvement.

In the realm of HER2-positive breast cancer management, navigating decision-making regarding newer treatments poses a significant challenge for oncologists, Tiwari begins. The crux of the matter lies in determining the optimal sequence of these treatments, a conundrum that currently lacks a definitive answer, she explains. The dynamic nature of medical advancements means that studies evaluating treatment efficacy are conducted within the framework of existing standards of care, which inevitably evolve with the approvals of novel drugs, according to Tiwari. Consequently, the pressing issue becomes how to effectively sequence these medications, a task growing increasingly complex across various subtypes of breast cancer, including HER2-positive, triple-negative, and hormone receptor–positive disease, Tiwari elucidates.

A pertinent question arises regarding the selection between a tucatinib (Tukysa)–based regimen and fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with HER2-positive breast cancer with CNS involvement, she expands. Drawing upon the findings from the phase 2 HER2CLIMB study (NCT02614794), which investigated the efficacy of trastuzumab plus capecitabine (Xeloda) and tucatinib in patients with HER2-positive metastatic breast cancer, it is evident that this regimen generates commendable efficacy in managing CNS disease, Tiwari says. Notably, a considerable sum of patients with brain metastases exhibited no requirement for additional treatment at the 1-year mark, Tiwari reports.

Navigating CNS metastases within the context of breast cancer treatment presents challenges, as systemic therapies often fall short in controlling disease progression, necessitating frequent surgical interventions and other therapeutic modalities, she continues. Thus, the 24.1% 1-year progression-free survival rate observed among patients with brain metastases in this trial underscores the promise of the HER2CLIMB regimen as a frontline treatment approach, Tiwari emphasizes. Although preliminary data exist regarding the use of trastuzumab deruxtecan in this patient population, comprehensive insights are pending the completion of ongoing trials, such as the phase 1b/2 DESTINY-Breast07 trial (NCT04538742), Tiwari says. Until then, the HER2CLIMB regimen remains a preferred choice in clinical practice, Tiwari concludes.

Shruti Tiwari, MD, discusses treatment sequencing in HER2+ breast cancer, highlighting how to treat these patients when they present with CNS involvement.

Shruti Tiwari, MD

Articles

Dr Tiwari on the Current Treatment Paradigms for HER2-Positive and HER2-Low Breast Cancers

Dr. Tiwari on Ongoing Research in HER2+/HER2-Low Breast Cancer

Dr Tiwari on Optimal Treatment Sequencing in HER2+ Breast Cancer