Dr Conlin on Targeting CNS Metastases in the Treatment of Breast Cancer

Alison K. Conlin, MD, medical oncologist, Providence Cancer Institute Franz Clinic, discusses the importance of targeting central nervous system (CNS) metastases in the treatment of patients with breast cancer, highlighting ongoing treatment investigations for this population.

Over the past 5 years, there has been significant progress in the treatment paradigm for patients with HER2-positive breast cancer with CNS metastases, particularly since the phase 2 HER2CLIMB study (NCT02614794) demonstrated the efficacy of tucatinib (Tukysa) in this population, Conlin begins. This efficacy was specifically noted in patients with untreated or progressive disease, he states. Recent data from a pooled analysis of the phase 2 DESTINY-Breast01 (NCT03248492), phase 3 DESTINY-Breast02 (NCT03523585), and phase 3 DESTINY-Breast03 (NCT03529110) trials presented at the 2023 ESMO Congress showed that fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) elicited an ORR of 45.2% in patients with treated or stable CNS metastases and an ORR of 45.5% in those with untreated or active CNS metastases Conlin explains. Although the presentation involved pooled data and lacked a randomized prospective study design, the results were notably impressive, she adds. These findings indicate that there are viable options for effectively controlling untreated CNS disease in patients with HER2-positive breast cancer, expanding the choices available for their treatment, Conlin says.

The evolving understanding of HER2-positive breast cancer with CNS metastases is prompting a reassessment of available treatment strategies, she continues. Notably, insights from the phase 3 KATHERINE study (NCT01772472) have highlighted that although patients with high-risk HER2-positive disease experience improved outcomes with ado-trastuzumab emtansine (Kadcyla; T-DM1) vs trastuzumab, they still experience CNS recurrence rates comparable withthose experienced by patients who receive trastuzumab if they don't achieve a pathologic complete response to T-DM1, Conlin emphasizes. As the oncology field recognizes the CNS as a site where disease recurrences can occur, research focuses are shifting toward exploring preventive measures, she elucidates.

Ongoing National Cancer Institute–sponsored research is investigating the potential of using an oral TKI, such as tucatinib, to prevent CNS disease in patients deemed cured of their breast cancer, Conlin expands. Existing data support the use of neratinib (Nerlynx), another oral TKI,for the prevention of secondary CNS disease, she explains. The phase 2 BRIDGET study (NCT05323955) is actively examining the feasibility of treating isolated CNS recurrence with local therapy and exploring the addition of a TKI to trastuzumab plus pertuzumab or T-DM1 to prevent future CNS metastases or overall disease progression, Conlin adds. This trial’sperspective underscores the evolving view of the CNS as a distinct consideration, not only as a potential separate entity but also as an integral part of overall systemic disease control strategies, she concludes.

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Alison K. Conlin, MD, discusses the importance of targeting central nervous system metastases in the treatment of patients with breast cancer, highlighting ongoing treatment investigations for this population.


Alison K. Conlin, MD, on unanswered questions regarding CDK4/6 inhibitors after prior progression on CDK4/6 inhibitors and QOL considerations in breast cancer.

Dr Conlin on CDK4/6 Inhibitor Sequencing and QOL in Breast Cancer

Alison K. Conlin, MD, medical oncologist, Providence Cancer Institute Franz Clinic, discusses unanswered questions regarding the use of CDK4/6 inhibitors after prior progression on CDK4/6 inhibitors and quality of life (QOL) considerations in patients with breast cancer.

Dr Conlin on CDK4/6 Inhibitor Sequencing in HR+/HER2– Breast Cancer

Current clinical trial results pose conflicting data regarding optimal CDK4/6 inhibitor sequencing in patients with hormone receptor (HR)–positive, HER2-negative breast cancer, Conlin says. The efficacy and safety of using additional CDK4/6 inhibitors in patients with this disease who have progressed on a prior CDK4/6 inhibitor remains unknown, Conlin explains. Providence Cancer Institute plans to conduct further research to address this question, Conlin notes.

Continuing CDK4/6 inhibition after progression on first-line CDK4/6 inhibitors is beneficial for some patients, but may not be the most effective or tolerable treatment strategy in all patients with HR-positive, HER2-negative disease, Conlin emphasizes. This decision should be informed by each patient’s progression level and ability to tolerate further CDK4/6 inhibition, according to Conlin.

Further data beyond phase 2 single-arm clinical trial findings are needed to determine the feasibility of sequencing CDK4/6 inhibitors upon progression, Conlin says. Until those research efforts read out, most patients with HR-positive, HER2-negative breast cancer should receive a first-line CDK4/6 inhibitor followed by another type of targeted therapy, Conlin explains.

Dr Conlin on The Importance of QOL Considerations in Breast Cancer

QOL is important to patients receiving breast cancer treatment, and the development of treatment plans should include conversations with each patient about their preferences and challenges, such as their ability or willingness to regularly come into the clinic to receive treatment, Conlin emphasizes. Other patients may want to avoid adverse effects (AEs) such as nausea or hair loss, which can affect their daily life, Conlin notes.

Efforts to improve patient QOL are embedded into oncology research and practice, as patients with cancer must often make sacrifices that affect their happiness and comfort when receiving treatment, according to Conlin. Even clinical trials that do not directly evaluate QOL outcomes can contribute to improved QOL for patients if they show efficacy and tolerability benefits with regimens that are easier to take and associated with fewer toxicities than standard treatments, Conlin explains. Shared decision making should be part of all treatment conversations with patients, Conlin concludes.

Alison K. Conlin, MD, discusses unanswered questions regarding the use of CDK4/6 inhibitors after prior progression on CDK4/6 inhibitors and quality of life considerations in patients with breast cancer.

Alison K. Conlin, MD, medical oncology, Providence Cancer Institute Franz Clinic, discusses the inception of the HER2-low breast cancer treatment landscape.

Movement in the breast cancer treatment landscape has been underscored by the development and approval of new agents and indications, Conlin explains. Recent data from clinical trials have identified HER2-low as a recognizable new subset of patients in the breast cancer space, Conlin adds.

With the treatment landscape within breast cancer continuing to grow, clinical research and enrolling patients to clinical trials will be vital to best identify optimal treatment strategies for different groups of patients, Conlin concludes.

Alison K. Conlin, MD, discusses the inception of the HER2-low breast cancer treatment landscape.


Dr. Conlin on the Implications of the HER2-Low Subset in Breast Cancer

Alison K. Conlin, MD, discusses the benefits of trastuzumab deruxtecan in HER2-low breast cancer.

Dr. Conlin on the Benefits of Trastuzumab Deruxtecan in HER2-Low Breast Cancer

Alison K. Conlin, MD, medical oncology, Providence Cancer Institute Franz Clinic, discusses the benefits of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-low breast cancer. 

The phase 3 DESTINY-Breast04 trial (NCT03734029) evaluated the safety and efficacy of the antibody-drug conjugate (ADC) trastuzumab deruxtecan vs physician’s choice therapy as second-line therapy in patients with HER2-low breast cancer.

The results showed that the ADC should be used in the second-line setting, Conlin says. Although there are many treatments available, trastuzumab deruxtecan is a great option with a high rate of survival, Conlin explains.

Moreover, the duration of response is prolonged with the agent, Conlin continues. As such, this offers patients more time to receive subsequent therapies, Conlin concludes. 

Alison K. Conlin, MD, discusses the benefits of trastuzumab deruxtecan in HER2-low breast cancer. 


Alison K. Conlin, MD, medical oncology, Providence Cancer Institute Franz Clinic, discusses the practice-changing data of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive breast cancer.

The phase 3 DESTINY-Breast03 trial (NCT03529110) evaluated the safety and efficacy of the antibody-drug conjugate (ADC) trastuzumab deruxtecan vs ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients with HER2-positive, unresectable or metastatic breast cancer.

The benefit in responses and progression-free survival elicited by trastuzumab deruxtecan compared with T-DM1 served as practice-changing data, Conlin says. In May 2022, 

the FDA granted regular approval to trastuzumab deruxtecan

 for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received an anti–HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within 6 months of therapy completion, based on data from DESTINY-Breast03.

Though the toxicity profile of trastuzumab deruxtecan should be discussed with patients, the high clinical benefit observed with the ADC also offers great promise for patients with HER2-positive breast cancer, Conlin concludes.

Alison K. Conlin, MD, discusses the practice-changing data of fam-trastuzumab deruxtecan-nxki in HER2-positive breast cancer.


Alison K. Conlin, MD

Articles

Dr Conlin on Targeting CNS Metastases in the Treatment of Breast Cancer

Dr Conlin on CDK4/6 Inhibitor Sequencing and QOL in Breast Cancer

Dr. Conlin on the Implications of the HER2-Low Subset in Breast Cancer

Dr. Conlin on the Benefits of Trastuzumab Deruxtecan in HER2-Low Breast Cancer

Dr. Conlin on the Practice-Changing Data of Trastuzumab Deruxtecan in HER2+ Breast Cancer