Dr Nanda on Treatment De-Escalation in HER2+ Breast Cancer and TNBC

Rita Nanda, MD, associate professor, medicine, director, Breast Oncology Program, University of Chicago Medicine, discusses the importance of neoadjuvant therapy for patients with HER2-positive breast cancer and triple-negative breast cancer (TNBC), as well as efforts to de-escalate treatment in the adjuvant setting.

Neoadjuvant therapy is the current standard of care for patients with stage II and III HER2-positive breast cancer and TNBC, Nanda begins. All patients with these disease stages should be offered neoadjuvant therapy, as their response to treatment in this setting informs the optimal selection of adjuvant approaches, Nanda says. Furthermore, clinical trials are evaluating the de-escalation of adjuvant therapy for patients who respond to neoadjuvant therapy.

For instance, the ongoing phase 2 ATEMPT 2.0 trial (NCT04893109) is assessing the use of adjuvant ado-trastuzumab emtansine (T-DM1; Kadcyla) followed by subcutaneous trastuzumab (Herceptin) vs paclitaxel plus subcutaneous trastuzumab in patients with newly diagnosed, stage I HER2-positive invasive breast cancer. To be eligible for trial enrollment, patients must be at least 18 years of age, have node-negative or micrometastatic breast cancer, and have an ECOG performance status of 0 or 1. Patients with bilateral breast cancers, multifocal disease, or multicentric disease are permitted to enroll onto the study provided that each individual tumor meets eligibility criteria. All tumors are required to be removed via modified radical mastectomy or a segmental mastectomy, with either an axillary dissection or sentinel lymph node biopsy.

Patients in the investigative arm will be randomly assigned to receive T-DM1 every 3 weeks for 6 cycles followed by trastuzumab every 3 weeks for 11 cycles. Patients in the control arm will receive paclitaxel for 4 cycles and trastuzumab every 3 weeks for 17 cycles, with the first 4 doses of each drug given concurrently. The trial’s primary end points are the incidence of clinically relevant toxicities and disease-free survival. Key secondary end points include safety, quality of life assessments, and overall survival.

Additional clinical trials are investigating novel adjuvant therapies that may reduce recurrence risk for patients who do not achieve a pathologic complete response with neoadjuvant therapy, Nanda concludes.

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Rita Nanda, MD, discusses efforts to de-escalate adjuvant therapy for patients with select breast cancers who responded to neoadjuvant therapy.

Dr Nanda on HER2-Low Status Testing in Early-Stage Breast Cancer

Rita Nanda, MD, associate professor, medicine, director, Breast Oncology Program, University of Chicago, UChicago Medicine, discusses the importance of testing for HER2-low status in patients with early-stage breast cancer.

Depending on the cancer center, the approach to HER2 testing has been limited to fluorescence in situ hybridization without incorporating immunohistochemical (IHC) analysis, Nanda begins. This practice often necessitates revisiting patients with unknown HER2 IHC status by performing IHC or conducting new biopsies on primary breast tumors, she says. It is common for patients to undergo a new biopsy when experiencing a recurrence following early-stage breast cancer, according to Nanda. The thorough examination of all tumor samples for HER2-low status is essential, particularly when considering the potential benefit of HER2-low–directed therapy, she explains.

The current IHC analysis methods may not be optimal for identifying patients eligible for treatment with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd), she says. Ongoing studies and the exploration of different biomarkers hold promise in refining patient selection criteria, Nanda explains. There remains considerable interest in further elucidating whether expanding access to testing or adopting alternative HER2 testing methodologies could better identify patients who would derive substantial benefit from this life-extending therapy, Nanda elucidates.

Accurately identifying HER2 status is vital, as it directly influences treatment decisions and patient outcomes, she expands, adding that accurate assessment is critical for determining the potential efficacy of targeted therapies, such as T-DXd, in patients with HER2-low breast cancer. Enhancing diagnostic capabilities through the exploration of novel biomarkers and testing methodologies is essential for optimizing patient care and ensuring that eligible patients receive appropriate and effective treatments, Nanda notes.

Furthermore, ongoing efforts are aimed at refining the breast cancer field’s understanding of HER2 expression patterns and patient responses to targeted therapies, she continues. These endeavors are driven by the goal of expanding access to life-extending treatments for a broader population of patients with HER2-low breast cancer, Nanda concludes.

Rita Nanda, MD, discusses the importance of testing for HER2-low status in patients with early-stage breast cancer.

Dr Nanda on the Evolution of CDK4/6 Inhibitor Treatment in HR+/HER2– Breast Cancer

Rita Nanda, MD, associate professor, medicine, director, Breast Oncology Program, University of Chicago, UChicago Medicine, discusses the evolution of treatment with CDK4/6 inhibitors in patients with hormone receptor (HR)–positive/HER2-negative breast cancer.

The current state of care for patients with HR-positive/HER2-negative breast cancer was discussed in a presentation at an 

® State of the Science Summit™ on breast cancer, with a focus on integrating CDK4/6 inhibitors into frontline therapy in combination with endocrine-based treatments, Nanda begins. However, there remains a question about next steps after patients progress on CDK4/6 inhibitors, she adds. New targeted therapies have emerged for patient subsets, such as those with 

Trials have yielded varied results regarding the continuation of CDK4/6 inhibitors in the second-line setting, Nanda continues. The phase 2 PACE trial (NCT03147287) demonstrated no benefit with continuing palbociclib (Ibrance) after progression on a prior CDK4/6 inhibitor in patients with HR-positive/HER2-negative metastatic breast cancer. However, the phase 2 MAINTAIN study (NCT02632045) showed modest benefit with this treatment approach in this patient population. Expectations are high for the phase 3 postMONARCH trial (NCT05169567), primary findings from which will be presented at the 2024 ASCO Annual Meeting, according to Nanda. postMONARCH is a robust randomized study exploring the continuation of abemaciclib (Verzenio) plus fulvestrant (Faslodex) in the second-line HR-positive, HER2-negative metastatic breast cancer setting following progression on a CDK4/6 inhibitor and endocrine therapy, Nanda explains, noting that this trial's results could provide clarity on the role of continuing CDK4/6 inhibitors in this context.

 mutations, elacestrant (Orserdu) is now a treatment option, and the combination of capivasertib (Truqap) and fulvestrant 

 pathway alterations, she expands. Furthermore, alpelisib (Piqray) and capivasertib are available for patients with 

 mutations, Nanda states. Despite these advancements, most patients lack 

The monarchE trial is anticipated to shed light on whether continuing CDK4/6 inhibitors is beneficial for patients without 

 pathway alterations, Nanda says. This trial's findings are eagerly awaited to guide treatment decisions in this setting, Nanda concludes.

Rita Nanda, MD, discusses the evolution of treatment with CDK4/6 inhibitors in patients with hormone receptor-positive/HER2-negative breast cancer.

Dr Nanda on the Evolution of Treatment For HER2-Low Breast Cancer

Rita Nanda, MD, associate professor, medicine, director, Breast Oncology Program, University of Chicago, UChicago Medicine, discusses the evolution of treatment options for patients with HER2-low breast cancer.

the FDA approval of fam-trastuzumab deruxtecan-nxki

(Enhertu) for patients with unresectable or metastatic HER2-low disease represents a significant milestone in oncology, Nanda begins. This regulatory decision has provided patients with HER2-low disease with a chance for prolonged progression-free survival and overall survival, she states. Looking ahead, a critical question arises regarding patients with HER2 levels falling below the conventional threshold, Nanda explains. The ongoing phase 3DESTINY-Breast06 trial (NCT04494425) aims to address this query by investigating trastuzumab deruxtecan's efficacy in patients with HER2-low disease, including those with HER2 levels greater than 0 but less than 1+ she adds.

Moreover, the challenge of optimizing treatment sequencing emerges, particularly for patients eligible for multiple antibody-drug conjugates (ADCs), Nanda continues. Patients with triple-negative breast cancer and those with hormone receptor (HR)–positive disease are candidates for sacituzumab govitecan-hziy (Trodelvy), and patient eligibility for this agent often overlaps with that for HER2-targeting ADCs, Nanda says. The critical inquiry revolves around determining the most effective sequence for TROP2-targeted ADCs and HER2-targeted ADCs in patients with HER2-low disease, according to Nanda. Although randomized data from ongoing trials are eagerly anticipated, data from current registry trials indicate that sequential administration of ADCs may not yield the anticipated efficacy for the second ADC, she elucidates.

Moving forward, there remains a pressing need to further comprehend the optimal use of ADCs in patients eligible for multiple therapies, Nanda continues. This necessitates ongoing research efforts and a forward-looking approach to elucidate the most effective treatment sequencing strategies, she adds. As oncologists navigate this evolution, the goal is to optimize therapeutic outcomes and improve the standard of care for patients with HER2-low disease, ensuring each patient receives the most beneficial treatment regimen tailored to their specific disease characteristics and treatment history, Nanda concludes.

Rita Nanda, MD, discusses the evolution of treatment options for patients with HER2-low breast cancer.

Rita Nanda, MD, assistant professor of medicine and associate director of the Breast Medical Oncology Program at the University of Chicago, discusses the potential of pembrolizumab (Keytruda) for the treatment of triple-negative breast cancer (TNBC). A recent small-scale trial showed treatment response for 18.5% of patients with PD-L1 positive TNBC.

The drug was well tolerated, and while 56% experienced some side effects, the vast majority of these side effects were very mild, easily managed, and did not result in treatment discontinuation, says Nanda.

A total of 32 women enrolled in the trial and 27 had evaluable disease. Of those 27 patients, five responded to the treatment, including one complete response and four partial responses.

The patients in the study were very heavily pretreated. Over half of them had three or more lines of chemotherapy prior to entering the study.

While this is a small, preliminary study, Nanda says the results are exciting and suggest a promising option for a subset of women with TNBC. Moving forward, research should focus on identifying the patients who will best respond to this therapy.

View more from the 2014 San Antonio Breast Cancer Symposium

Rita Nanda, MD, assistant professor of medicine and associate director of the Breast Medical Oncology Program at the University of Chicago, discusses the potential of pembrolizumab (Keytruda) for the treatment of triple-negative breast cancer (TNBC).  A recent small-scale trial showed treatment response for 18.5% of patients with PD-L1 positive TNBC.

Rita Nanda

Articles

Dr Nanda on Treatment De-Escalation in HER2+ Breast Cancer and TNBC

Dr Nanda on HER2-Low Status Testing in Early-Stage Breast Cancer

Dr Nanda on the Evolution of CDK4/6 Inhibitor Treatment in HR+/HER2– Breast Cancer

Dr Nanda on the Evolution of Treatment For HER2-Low Breast Cancer

Dr. Nanda On Pembrolizumab Potential for TNBC