Dr Advani on the Evaluation of Ribociclib/Endocrine Therapy in HR+/HER2– Breast Cancer

Pooja Advani, MBBS, MD, hematologist/oncologist, Mayo Clinic Comprehensive Cancer Center, discusses the evaluation of ribociclib (Kisqali) plus endocrine therapy for the adjuvant treatment of patients with hormone receptor (HR)–positive/HER2-negative breast cancer.

The phase 3 multicenter, randomized, open-label NATALEE trial (NCT03701334) evaluated the efficacy and safety of ribociclib in combination with endocrine therapy in this patient population. The NATALEE enrollment criteria broadened the pool of patients with high-risk, estrogen receptor–positive, HER2-negative early breast cancer who are eligible to receive CDK4/6 inhibitors plus endocrine therapy to enhance their survival prospects, Advani begins. Unlike the phase 3 monarchE trial (NCT03155997) of endocrine therapy with or without abemaciclib (Verzenio), which only enrolled patients with high-risk disease, the NATALEE trial also included high-risk patients with stage II disease, she explains. Another point of contrast between the 2 studies was the dosage of ribociclib administered, which was lower in NATALEE than that used in the metastatic setting—400 mg instead of 600 mg, Advani notes.

Additionally, in NATALEE, ribociclib treatment spanned 3 years compared with the standard 2-year duration of abemaciclib treatment, she expands. Despite these unique characteristics, the NATALEE trial successfully achieved its primary end point: improvement in invasive disease-free survival (IDFS) with adjuvant ribociclib combined with a non-steroidal aromatase inhibitor (NSAI) vs an NSAI alone. However, the overall survival data from NATALEE are premature as most patients have yet to complete the prespecified 3-year ribociclib regimen, she elucidates. Ribociclib is currently pending FDA approval for patients with HR-positive/HER2-negative breast cancer, and thus cannot be currently used in the clinic, Advani says, adding that the absolute IDFS benefit with ribociclib in the current analysis was 3.3%, which raises questions about the clinical significance of this agent. Furthermore, the occurrence of grade 3 or higher liver adverse effects in 8.3% of patients who received ribociclib plus an NSAI warrants careful consideration, she reports.

If the NATALEE regimen receives FDA approval for patients with HR-positive/HER2-negative breast cancer, providing another CDK4/6 inhibitor treatment option, patients meeting monarchE enrollment criteria should receive the monarchE regimen because the monarchE data have longer follow-up compared with those from NATALEE. For patients not meeting monarchE criteria or those intolerant to abemaciclib, ribociclib could be considered, particularly for those with high-risk disease, Advani concludes.

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Pooja Advani, MBBS, MD, discusses the use of ribociclib plus endocrine therapy for patients with hormone receptor–positive, HER2– breast cancer.


Dr Advani on the Advantages of Liquid Biopsy in Metastatic Breast Cancer

Pooja Advani, MBBS, MD, hematologist/oncologist, Mayo Clinic Comprehensive Cancer Center, discusses the advantages of utilizing a liquid biopsy in metastatic breast cancer, as well as highlights unanswered questions on how to most effectively utilize circulating tumor DNA (ctDNA) assays to improve patient outcomes in this space.

Liquid biopsy plays a crucial role in the development of management strategies for patients with metastatic disease, particularly those with hormone receptor (HR)–positive, HER2-negative breast cancer, Advani begins. It enables the detection of mutations for which targeted therapies are available. This includes 

 mutations, where elacestrant (Orserdu) can be used; 

 mutations, which can be treated with alpelisib (Piqray) plus fulvestrant (Faslodex); and 

 mutations, which can be treated with capivasertib (Truqap) in combination with fulvestrant.

Moreover, liquid biopsy facilitates patient enrollment in biomarker-specific clinical trials, Advani continues. By detecting specific biomarkers in liquid biopsy, clinicians can refer patients to relevant clinical trials, optimizing their treatment options and potential outcomes, she explains.

Compared with traditional tissue biopsies, liquid biopsies offer several advantages, including ease of collection and better clonal representation, Advani states. However, the primary challenge lies in utilizing ctDNA for minimal residual disease (MRD) detection and monitoring, she explains. Clinicians are exploring the feasibility of tests with high sensitivity, specificity, and predictive value that can be performed in a serial or longitudinal fashion for MRD assessment, Advani says. Additionally, determining how to act upon these MRD detection findings remains a significant consideration, Advani notes.

Although liquid biopsy holds promise for personalized cancer management and clinical trial enrollment, further research is needed to refine its role in MRD detection and to determine optimal strategies for acting upon MRD findings to enhance patient care, Advani concludes.

Pooja Advani, MBBS, MD, discusses the advantages of using liquid biopsy in metastatic breast cancer.

Pooja Advani, MBBS, MD, discusses key advancements that have occurred for the treatment of patients with triple-negative breast cancer.

Dr Advani on Advancements in the Treatment of TNBC 

Pooja Advani, MBBS, MD, hematologist/oncologist, Mayo Clinic Comprehensive Cancer Center, discusses key advancements that have occurred over the past few years for the treatment of patients with triple-negative breast cancer (TNBC) and highlights planned and ongoing breast cancer research she is involved in.

Discussions are underway regarding the sequencing of treatments in TNBC, a condition for which therapeutic options were previously limited, Advani begins. This presents an exciting yet challenging period of time. A significant development to highlight within this treatment paradigm is the analysis of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in the phase 3 DESTINY-Breast04 trial (NCT03734029), Advani elucidates. Although this trial involved a relatively small cohort of patients with TNBC, there was a notable improvement observed in both median progression-free survival (PFS) and overall survival (OS), she adds.

Additionally, sacituzumab govitecan-hziy (Trodelvy) has demonstrated utility and gained regulatory approval in TNBC, Advani expands. Studies have shown activity with this agent across HER2-low and HER2-negative disease, regardless of TROP-2 expression, she notes. Furthermore, when considering antibody-drug conjugates (ADCs) for patients with TNBC, there are now 2 options available in the second line and beyond, Advani says.

Clinicians should also prioritize testing for germline 

 mutations to continually evaluate TNBC status in the metastatic setting and identify potential candidates for PARP inhibitor therapy, Advani continues. Furthermore, personalization of therapy, focusing on efficacy and toxicity, is paramount, and is based on results from tissue or liquid biopsy, according to Advani. Functional assays are needed to appropriately match patients with the most suitable treatment regimens, she adds.

Overall, Advani is enthusiastic about participating in a project using functional assays to predict responses to immune checkpoint inhibitors across various tumor types. Tissue biopsies will be collected from patients, and live tumor fragments will undergo multi-photon imaging to assess their likelihood of responding to immune checkpoint inhibitors, offering personalized treatment insights, she concludes.

Dr Advani on Advancements in the Treatment of TNBC

Dr Advani on the Role of Capivasertib Plus Fulvestrant in HR+/HER2– Breast Cancer

Pooja Advani, MBBS, MD, hematologist/oncologist, Mayo Clinic Comprehensive Cancer Center, discusses the potential utilization of capivasertib (Truqap) plus fulvestrant (Faslodex) in select hormone receptor (HR)–positive, HER2-negative breast cancer.

FDA approved the AKT inhibitor capivasertib

 in combination with fulvestrant for patients with HR–positive, HER2-negative metastatic or locally advanced disease and 1 or more mutations in the 

 pathway, as detected by an FDA approved companion test, Advani begins. Patients were also required to have experienced disease progression after at least 1 endocrine-based regimen in the metastatic setting, or recurrence on or within 12 months of completing adjuvant therapy.

The regulatory decision was based on data from the phase 3 CAPItello-291 trial (NCT04305496), Advani states. This registrational multicenter trial enrolled over 700 patients in the metastatic setting, she details. The study encompassed the patient population that received the capivasertib and fulvestrant combination, but a specific focus was placed on the pathway-altered population, Advani adds.

Results showed that the combination produced a median progression-free survival of 7.3 months vs 3.1 months (95% CI, 2.0-3.7) for those treated with placebo plus fulvestrant (n = 134; HR 0.50; 95% CI, 0.38, 0.65; 

 < .0001). Although the combination demonstrated significant benefits in both the overall patient population and in those with the specified alterations, the current regulatory approval is specifically granted for patients with these identified alterations, Advani clarifies. This represents a noteworthy development and an additional therapeutic option for this subgroup of patients, Advani explains.

Notably, the observed rate of hyperglycemia with the combination was lower compared with the PIK3CA inhibitor alpelisib (Piqray) in combination with fulvestrant. This reduced incidence is particularly important for the oncology community, as managing this adverse effect can often present a substantial challenge in clinical practice. Overall, the favorable safety profile of capivasertib plus fulvestrant further enhances the appeal of this combination as a viable and well-tolerated treatment option for patients in the metastatic setting, especially those with 

Pooja Advani, MBBS, MD, discusses the potential utilization of capivasertib plus fulvestrant in hormone receptor–positive, HER2-negative breast cancers with PIK3/AKT/PTEN pathway alterations. 

Pooja Advani, MBBS, MD

Articles

Dr Advani on the Evaluation of Ribociclib/Endocrine Therapy in HR+/HER2– Breast Cancer

Dr Advani on the Advantages of Liquid Biopsy in Metastatic Breast Cancer

Dr Advani on Advancements in the Treatment of TNBC

Dr Advani on the Role of Capivasertib Plus Fulvestrant in HR+/HER2– Breast Cancer