
Ruth O’Regan, MD, professor, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, associate director, Clinical Research, University of Wisconsin Carbone Cancer Center, discusses the utility of CDK4/6 inhibitors in breast cancer.

CDK4/6 inhibitors have demonstrated improved efficacy in metastatic hormone receptor–positive, HER2-negative breast cancer by way of progression-free survival, and, in some instances, overall survival compared with endocrine therapy alone. 

To date, there are limited data on ​the role of CDK4/6 inhibitors in HER2-positive and triple-negative breast cancer, ​O'Regan explains.

When palbociclib (Ibrance) was initially investigat​ed, the field evaluated various cell lines to deduce where the therapy was most effective​, says O'Regan. ​Moreover, estrogen receptor (ER)–positive luminal cell lines appeared to derive to most benefit. 

However, ​these data also indicated that HER2-positive cell lines, whether they were ER-positive or ER-negative, also benefited from palbociclib, O’Regan concludes. 

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Ruth O’Regan, MD, discusses the utility of CDK4/6 inhibitors in breast cancer.

Dr. O’Regan on the Utility of CDK4/6 Inhibitors in Breast Cancer 

Ruth O’Regan, MD, professor, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, associate director, Clinical Research, University of Wisconsin Carbone Cancer Center, discusses emerging CDK4/6 inhibitor combinations in breast cancer.

Several ongoing clinical trials are examining CDK4/6 inhibitors in combination with estrogen receptor inhibitors and PI3K/mTOR pathway inhibitors, O’Regan says. 

Although the data appear promising, a triplet regimen may not be superior to CDK4/6 inhibitors plus endocrine therapy alone, adds O’Regan. However, direct comparisons are needed to confirm that theory. 

Additionally, the triplet regimens are associated with increased but not overlapping toxicities, O’Regan explains.

Ultimately, the risk-benefit ratio with the triplet may not outweigh the impressive responses observed with the doublet in the first-line setting. Instead, PI3K/mTOR inhibition may be better suited for patients who are resistant to endocrine therapy, concludes O’Regan.

Ruth O’Regan, MD, discusses emerging CDK4/6 inhibitor combinations in breast cancer.  



Dr. O'Regan on Emerging CDK4/6 Combinations in Breast Cancer 

Ruth O’Regan, MD, professor, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, associate director, Clinical Research, University of Wisconsin Carbone Cancer Center, discusses biomarkers of response to CDK4/6 inhibitors in breast cancer.

Extensive research regarding potential biomarkers of response to CDK4/6 inhibitors has been done in breast cancer, says O’Regan. Despite looking at proteins involved in the retinoblastoma pathway and the CDK4/6 pathways, researchers have not been able to validate a biomarker of response apart from the estrogen receptor (ER).

Moreover, emerging evidence suggests that cancers that are ER negative may benefit from CDK4/6 inhibitors, says O’Regan. However, more research is needed to determine exactly which subtypes benefit the most as well as understand the nuances of response in the early and metastatic settings, concludes O’Regan.

Ruth O’Regan, MD, discusses biomarkers of response to CDK4/6 inhibitors in breast cancer.

Dr. O’Regan on Biomarkers of Response to CDK4/6 Inhibitors in Breast Cancer

Ruth O’Regan, MD, professor, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, associate director, Clinical Research, University of Wisconsin Carbone Cancer Center, discusses patient education as biosimilars are implemented into practice for breast cancer.

As biosimilars begin to integrate into breast cancer treatment, physicians must be prepared to answer patient questions regarding what are biosimilars, if they are as effective as the original drugs, and more, explains O’Regan. The University of Wisconsin Carbone Cancer Center is preparing a patient education packet about biosimilars to allow patients to read the information on their own.

O’Regan believes the bigger challenge will be in educating patients who have received treatment before rather than newly diagnosed patients. Patients with metastatic HER2-positive metastatic breast cancer who have been on treatment for a few years may not be as receptive to using biosimilars, concludes O’Regan.

Ruth O’Regan, MD, discusses patient education as biosimilars are implemented into practice for breast cancer.

Dr. O'Regan on Biosimilar Education in Breast Cancer

Ruth O’Regan, MD, professor, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, associate director, Clinical Research, University of Wisconsin Carbone Cancer Center, discusses the prognostic value of pathologic complete response (pCR) in HER2-positive breast cancer. 

Achieving a pCR to neoadjuvant therapy is associated with a favorable prognosis in this patient population as compared with those who have residual disease, says O’Regan. 

Notably, hormone receptor status appears to influence this prognostic value. For example, patients with HER2-positive, estrogen receptor&shy; (ER)—negative disease appear to derive a stronger benefit from achieving pCR as opposed to patients with HER2-positive, ER-positive disease, explains O’Regan. 

In general, the proportion of patients who achieve a pCR is lower in those with HER2-positive, ER-positive disease; therefore, it may be beneficial that pCR holds more prognostic value in HER2-positive, ER-negative cancer, O’Regan concludes. 

Ruth O’Regan, MD, discusses the prognostic value of pathologic complete response in HER2-positive breast cancer. 
 

Dr. O'Regan on Prognostic Value of pCR in HER2+ Breast Cancer

Ruth O’Regan, MD, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, discusses the role of chemotherapy as treatment continues to advance in breast cancer.

Chemotherapy is likely to stay in the treatment armamentarium in breast cancer, at least in the foreseeable future, O’Regan says. This is particularly the case in HER2-positive disease and in triple negative breast cancer, where chemotherapy plays a crucial role in the treatment sequence. However, the field of estrogen receptor (ER)—positive breast cancer seems to be moving away from chemotherapy.

Even if a patient with ER-positive disease has positive lymph nodes, they still might not benefit from chemotherapy if they have a low recurrence score. Interestingly, O’Regan adds, even patients with ER-positive disease who are at a high risk of recurrence typically do not benefit much from chemotherapy, although they are treated with it because there are no other options. Chemotherapy with CDK4/6 inhibitors might be an answer, O’Regan concludes.

Dr. O'Regan on Future of Chemotherapy in Breast Cancer

Ruth O’Regan, MD, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, discusses the impact of targeted agents in patients with HER2-positive breast cancer.

Chemotherapy still plays an important role in this subset of patients with breast cancer, but the HER2-targeted agents trastuzumab (Herceptin) and pertuzumab (Perjeta) have transformed the field, says O’Regan. HER2-positive breast cancer is an aggressive disease with a very high risk of recurrence, but new treatment strategies are curing some patients. New agents have completely changed the biology of the disease, she adds.

One of the biggest unanswered questions for physicians working in HER2-positive disease, says O’Regan, is figuring out how to administer less treatment in the adjuvant setting, while still providing the same clinical benefit to patients.

Targeted agents have markedly improved outcomes in this patient population, she adds. In the metastatic setting, the median survival for these patients is currently around 5 years. Until trastuzumab and pertuzumab came to the forefront of treatment, survival for patients with metastatic disease was less than 1 year.

Ruth O’Regan, MD, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, discusses the impact of targeted agents in HER2-positive breast cancer.

Dr. O'Regan on Impact of Targeted Agents in HER2+ Breast Cancer

Ruth O’Regan, MD, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, discusses biosimilar education in oncology.

O’Regan says that the best way for the oncology field to familiarize themselves with the concept of biosimilars is talking about them at continuing medical education meetings and national conferences. This will get those in the community to know the names of these agents, as well as the work behind them. Additionally, she says that talking to pharmacists, institutions, and nurses to make sure they know about biosimilars is key.

At the University of Wisconsin School of Medicine and Public Health, O’Regan says that physicians look at the formulary and whether there is a cheaper option than the original drug. If one is available, she says they would definitely consider using the biosimilar. Education needs to be done at the institution level, but there also needs to be information given out at meetings, O’Regan concludes.

Ruth O’Regan, MD, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, discusses biosimilar education in oncology.
 

Dr. O'Regan Discusses Biosimilar Education in Oncology

Ruth O’Regan, MD, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, discusses the status of biosimilars in oncology.

Biosimilars are beginning to take off in the field of oncology, explains O’Regan. Data on trastuzumab (Herceptin) biosimilars have been presented from randomized studies, demonstrating similar safety and immunogenicity profiles. Though these biosimilars may be ready for use in practice, says O’Regan, patients who have been on trastuzumab for years may not be comfortable making the switch to the biosimilar.

Nonetheless, biosimilars are an exciting breakthrough in oncology, and there are those in development outside of breast cancer, including those that physicians use as supportive agents, notes O’Regan. Additionally, different methods of administration are being explored, such as a subcutaneous injection. There is no doubt that biosimilars will have an impact on the field of oncology, says O’Regan, but the hope is that they will ultimately decrease the cost of cancer therapy.

Dr. O'Regan on the Status of Biosimilars in Oncology

Ruth O’Regan, MD, division head, Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, discusses biomarker research in breast cancer.

Molecular assays are used to make decisions of whether to give chemotherapy to patients or for prognostic reasons. According to O’Regan, it would interesting to use one of the existing assays, such as 21-Gene Recurrence Score, to determine which patients need a more intensive treatment.

Currently, no RNA has been extracted but that is something that could make sense as a biomarker for these patients.

Ruth O'Regan, MD

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