Dr Kalinsky on the postMONARCH Study in HR+/HER2– Advanced Breast Cancer

“One thing that’s worth noting about [the efficacy outcomes with abemaciclib plus fulvestrant] is [they were] not dependent on mutations that patients had; there was benefit [with the regimen vs placebo plus fulvestrant], regardless of whether patients had 

 mutations or mutations in the PI3K/AKT pathway.”

Kevin Kalinsky, MD, MS, professor, Department of Hematology and Medical Oncology, director, Division of Medical Oncology, Department of Hematology and Medical Oncology, Emory University School of Medicine; Louisa and Rand Glenn Family Chair in Breast Cancer Research, director, Glenn Family Breast Center, director, Breast Medical Oncology, Winship Cancer Institute of Emory University, discusses the 

outcomes of the phase 3 postMONARCH study (NCT05169567)

 for patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer.

Notably, findings from the randomized trial were shared at the 

. Kalinsky begins by saying that the postMONARCH study was a significant trial. Previous phase 2 studies had yielded inconsistent results on whether continuing a CDK4/6 inhibitor and switching hormonal therapy was beneficial for patients progressing on prior hormonal therapy and CDK4/6 inhibitors. Two studies with palbociclib (Ibrance) in this population had negative outcomes, whereas a trial with ribociclib (Kisqali) showed a positive effect, he reports, noting that postMONARCH evaluated abemaciclib (Verzenio) plus fulvestrant (Faslodex) in this population, providing clarity through a robust phase 3 design.

This large, randomized, placebo-controlled trial included 368 patients, Kalinsky continues. Patients previously treated with an aromatase inhibitor and a CDK4/6 inhibitor were randomly assigned to receive fulvestrant monotherapy or fulvestrant combined with abemaciclib. The results demonstrated an improvement in progression-free survival with the combination treatment, he shares. Notably, the greatest benefit was observed in patients with prior palbociclib use and those with non-visceral, bone-only disease.

An important aspect of the study was its independence from specific genetic mutations, Kalinsky expands. The treatment benefit with the combination was observed regardless of the presence of 

 mutations or alterations in the PI3K/AKT pathway. This finding highlights the broad applicability of the abemaciclib and fulvestrant combination as a potential treatment strategy for patients with HR-positive, HER2-negative advanced breast cancer, he concludes.

Videos

Kevin Kalinsky, MD, MS, discusses outcomes of the phase 3 postMONARCH study in hormone receptor–positive, HER2-negative advanced breast cancer.

Kevin Kalinsky, MD, MS, discusses questions regarding the utility and implementation of genomic testing approaches in hormone receptor–positive breast cancer. 

Dr Kalinsky on Unanswered Questions Regarding Genomic Testing in HR+ Breast Cancer

Kevin Kalinsky, MD, MS, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, director, the Glenn Family Breast Center, Breast Medical Oncology, Louisa and Rand Glenn Family Chair in Breast Cancer Research, Winship Cancer Institute of Emory University, discusses remaining questions regarding the utility and implementation of genomic testing approaches in patients with early-stage hormone receptor (HR)–positive breast cancer.

The use of genomic assays in guiding treatment decisions for patients with HR-positive, HER2-negative breast cancer presents several ongoing challenges, particularly in pre-menopausal patients and those with more than 3 involved lymph nodes, Kalinsky begins.

In node-negative disease, the benefit of chemotherapy in this patient population is not yet confirmed, he says. Uncertainty exists regarding whether the observed benefits stem from direct tumor biology differences between pre-menopausal and post-menopausal patients or from the induction of menopause by chemotherapy, Kalinsky explains. This raises questions surrounding the applicability of genomic assays, which are often developed and validated in post-menopausal populations, to pre-menopausal patients. Moreover, the role of genomic assays in guiding treatment decisions for patients with more than 3 involved lymph nodes remains unclear due to the limited prospective data available, Kalinsky adds.

Globally, disparities in access to genomic assays pose challenges to equitable cancer care, Kalinsky continues. Not all countries have equal access to these assays, leading to discrepancies in treatment decision-making and outcomes across different regions and populations, he says.

Addressing these challenges requires efforts to standardize the use of genomic assays and ensure equitable access to these technologies worldwide, Kalinsky states. He identifies the utilization of artificial intelligence (AI) as 1 potential solution to standardize and optimize genomic assay approaches. AI-driven algorithms can analyze large datasets and identify patterns in tumor biology, helping to tailor treatment decisions based on individual patient characteristics more effectively, he explains.

Overall, genomic assays hold promise in guiding treatment decisions for HR-positive, HER2-negative breast cancer, but controversies and challenges remain. Standardizing genomic assay approaches and addressing global disparities in access to these technologies are essential steps toward improving the effectiveness and equity of breast cancer care, Kalinsky concludes.

Kevin Kalinsky, MD, MS, associate professor, the Department of Hematology and Medical Oncology, Emory University School of Medicine, director, the Glenn Family Breast Center, Breast Medical Oncology, Louisa and Rand Glenn Family Chair in Breast Cancer Research, Winship Cancer Institute of Emory University, discusses the evolving treatment landscape for patients with triple-negative breast cancer (TNBC) and how to best sequence antibody-drug conjugates (ADCs) within this population.

Recent treatment advances have been made for patients with TNBC, specifically in those with PD-L1–positive tumors, Kalinsky begins. Patients with PD-L1-positive tumors account for approximately 40% of the TNBC population, and these patients are treated with chemotherapy and immunotherapy with pembrolizumab (Keytruda), Kalinsky says.

Additionally within the TNBC space, the ADC sacituzumab govitecan-hziy (Trodelvy) is approved by the FDA for use in patients with locally advanced or metastatic disease who have previously received 2 or more systemic therapies, including at least 1 in the metastatic setting. Patients with TNBC harboring germline 

 mutations can also be treated with PARP inhibitors, Kalinsky continues.

For patients who have unresectable or metastatic HER2-low breast cancer, fam-trastuzumab deruxtecan-nxki (Enhertu) is an available treatment option. The emergence of trastuzumab deruxtecan for patients with metastatic HER2-low disease has represented one of the biggest advancements in the breast cancer space, Kalinsky notes. HER2-low is defined as 1+ or 2+ based upon immunohistochemistry and being gene non-amplified, Kalinsky continues. Within the phase 3 DESTINY-Breast04 trial (NCT03734029) that led to the approval of trastuzumab deruxtecan for patients with HER2-low breast cancer, a benefit was also observed with the ADC in a subset of patients with TNBC, Kalinsky explains.

Given the vast array of treatment options available for patients with TNBC, it is important to consider how to best sequence these approaches, specifically regarding the ADCs, Kalinsky emphasizes. Given that sacituzumab govitecan was approved and showed an overall survival benefit specifically in patients with TNBC, this tends to be the preferred initial ADC given to these patients, Kalinsky concludes.

Kevin Kalinsky, MD, MS, discusses the evolving treatment landscape for patients with triple-negative breast cancer and how to best sequence antibody-drug conjugates within this population.

Dr. Kalinsky on the Evolving Treatment Landscape and Sequencing ADCs in TNBC

Kevin Kalinsky, MD, MS, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, director, Glenn Family Breast Center, Breast Medical Oncology, Louisa and Rand Glenn Family Chair in Breast Cancer Research, Winship Cancer Institute of Emory University, discusses the role of chemotherapy with ovarian function suppression and hormonal therapy for premenopausal patients withhormone receptor (HR)–positive/HER2-negative breast cancer.

Genomic assays have established clinical utility for patients with HR-positive/HER2-negative breast cancer, including those with node-negative disease and node-positive disease, where 1 to 3 lymph nodes are involved, Kalinsky explains.

However, questions remain from the phase 3 TAILORx trial (NCT00310180), including whether high-risk, premenopausal patients require chemotherapy in addition to ovarian function suppression plus hormonal therapy, Kalinsky explains. A recently approved, National Cancer Institute–sponsored trial will evaluate hormonal therapy plus ovarian function suppression with or without chemotherapy in a randomized setting, Kalinsky adds.

Studies like the randomized trial will further evaluate if high-risk, premenopausal patients with HR-positive, HER2-negative breast cancer require chemotherapy, Kalinsky concludes

Kevin Kalinsky, MD, MS, discusses the role of chemotherapy with ovarian function suppression and hormonal therapy for premenopausal patients with HR–positive/HER2-negative breast cancer.


Dr. Kalinsky on Chemotherapy for Premenopausal Patients With HR+/HER2- Breast Cancer

Caroline Seymour is your initial point of contact for the 

™. She joined the company in 2018 as an assistant editor, with expertise in video production and print/digital publication. Email: cseymour@onclive.com​ 

 News Network: On Location at the 2022 ASCO Annual Meeting. Each day, we will broadcast a series of interviews with top thought leaders, to learn their thoughts and reactions to data presented across oncology during the conference.

We are reporting from the 2022 ASCO Annual Meeting!

Get ready for highlights of some of the top news presented each day during the meeting—and soon we’ll speak with Drs Charu Aggarwal, Bradley McGregor, Robert Coleman, and Kevin Kalinsky, on what pivotal lung, genitourinary, gynecologic and breast cancer studies they are most excited about.

Treatment with trastuzumab deruxtecan doubled progression-free survival and reduced the risk of death by 36% compared with physician's choice of chemotherapy for patients with HER2-low, hormone receptor–positive metastatic breast cancer in findings from the phase 3 DESTINY-Breast04 study that were simultaneously published in the 

Ribociclib plus endocrine therapy led to a statistically significant improvement in progression-free survival in patients with hormone receptor–positive, HER2-negative unresectable or metastatic breast cancer with tumor progression following treatment with a CDK4/6 inhibitor in findings from the randomized phase 2 MAINTAIN trial.

A subgroup analysis of the phase 3 KEYNOTE-826 trial showed that pembrolizumab plus chemotherapy with or without bevacizumab prolonged progression-free survival and overall survival versus placebo plus chemotherapy with or without bevacizumab irrespective of bevaczumab use, histology, platinum use, and prior chemoradiation therapy and provided clinically meaningful benefits similar to the broader population of patients with persistent, recurrent, or metastatic cervical cancer.

Finally, rucaparib led to a significant improvement inprogression-free survival as first-line maintenance therapy in patients with ovarian cancer regardless of biomarker status in the phase 3 ATHENA-MONO trial. 

Please be sure to check out more of our coverage from the 2022 ASCO Annual Meeting at OncLive.com.

 News Network: On Location, I’m Caroline Seymour.

OncLive® will be LIVE with OncLive® News Network: On Location at the 2022 ASCO Annual Meeting. Each day, we will broadcast a series of interviews with top thought leaders, to learn their thoughts and reactions to data presented across oncology during the conference.

Latest in Lung, Genitourinary, Gynecologic, and Breast Cancers From ASCO 2022: Drs Charu Aggarwal, Bradley McGregor, Robert Coleman, and Kevin Kalinsky

Kevin Kalinsky, MD, MS, director of the Glenn Family Breast Center and Breast Medical Oncology at Winship Cancer Institute, and acting associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, discusses the potential of antibody-drug conjugates (ADCs) across breast cancer subtypes.

ADCs have been an important therapy for patients with HER2-positive breast cancer, Kalinsky says. For example, trastuzumab emtansine (Kadcyla) has shown benefit in those with metastatic HER2-positive disease, as well as those with residual disease. These agents are beginning to be considered in other disease subtypes, Kalinsky says.

One such ADC is sacituzumab govitecan-hziy (Trodelvy), which was 

patients with metastatic triple-negative breast cancer

 who have received at least 2 prior therapies for metastatic disease. Additionally, the agent is currently being evaluated in patients with hormone receptor–positive and HER2-negative disease.

Fam-trastuzumab deruxtecan-nxki (Enhertu) is another option that was 

. Early data have suggested that this agent may have a role in patients with HER2-low disease, as response rates have indicated beneficial activity, Kalinsky concludes.

Kevin Kalinsky, MD, MS, discusses the potential of antibody-drug conjugates across breast cancer subtypes.

Dr. Kalinsky on the Potential of ADCs Across Breast Cancer Subtypes

Kevin Kalinsky, MD, assistant professor of Medicine at Columbia University Medical Center, discusses the potential advantages of optical imaging for patients with HER2-positive breast cancer. 

Some patients with breast cancer are unable to tolerate MRIs, which makes non-invasive optical imaging beneficial, explains Kalinsky. There is no intravenous injection needed, allowing it to be relatively quick and inexpensive. 

Kevin Kalinsky, MD, assistant professor of Medicine at Columbia University Medical Center, discusses the potential advantages of optical imaging for patients with HER2-positive breast cancer.

Dr. Kalinsky on Optical Imaging for HER2+ Breast Cancer

Kevin Kalinsky, MD, assistant professor of Medicine at Columbia University Medical Center, discusses a phase I study of ruxolitinib (Jakafi) in combination with trastuzumab (Herceptin) in metastatic HER2-positive breast cancer.

Ruxolitinib, a JAK2 inhibitor, was given in combination with trastuzumab to patients who have progressed on trastuzumab. This non-chemotherapy regimen is taken orally, familiar to patients previously who were treated with trastuzumab.

Results showed the combination was well tolerated without any observable toxicities. A multi-centered phase II trial is ongoing.

Kevin Kalinsky, MD

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