Bhuvaneswari Ramaswamy, MD, assistant professor, The Ohio State University (OSU) Medical Center, breast medical oncologist, Translational Therapeutics Program, section chief, Breast Medical Oncology, director, Medical Oncology Fellowship Program in Breast Cancer, The Ohio State College of Medicine, OSU Cancer Center (OSUCC)–James, discusses the importance of real-world data when considering the efficacy of the CDK 4/6 inhibitor palbociclib (Ibrance) in hormone receptor (HR)–positive breast cancer.

The current treatment landscape of HR-positive breast cancer involves an array of targeted and biologically relevant therapies that have substantially improved patient outcomes, Ramaswamy begins. Among these are CDK4/6 inhibitors, which are considered a standard of care in this space.

Although palbociclib has been widely studied in clinical trials, there has been some conflicting evidence regarding its role and benefit in real-world populations, Ramaswamy states. Several prospective datasets have shown that this agent improves overall survival (OS) in the metastatic setting, Ramaswamy says. However, the phase 3 PALOMA-2 trial (NCT01740427), demonstrated that palbociclib plus the aromatase inhibitor letrozole (Femara) did not provide a survival benefit for postmenopausal patients, Ramaswamy details.

Real-world data are vital to confirming the real-world effectiveness and tolerability of palbociclib, as well as clarifying the sequencing of CDK4/6 inhibitors in practice. Palbociclib is still commonly utilized in the frontline settingdespite results from PALOMA-2, and real-world data has shown an OS benefit with this agent, Ramaswamy says. Additionally, many clinical trial populations are not representative of patients that present in clinic and real-world data can identify efficacy-effectiveness gaps for these agents, she adds.

Investigators have suggested that differences in study design, disease biology, or varying targets, could be affecting OS outcomes in randomized studies, Ramaswamy continues. Real-world data can also address these lingering questions regarding conflicting clinical trial results.

Lastly, data from these trials can help identify which patients may benefit from initial treatment with an anti-estrogen approach rather than a CDK4/6 inhibitor, which could help combat the development of treatment resistance, Ramaswamy concludes.

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Bhuvaneswari Ramaswamy, MD, discusses the importance of real-world data when considering the efficacy of the CDK 4/6 inhibitor palbociclib in hormone receptor–positive breast cancer.


Dr. Ramaswamy on the Real-World Data Implications of Palbociclib in HR-Positive Breast Cancer

Bhuvaneswari Ramaswamy, MD, member, Translational Therapeutics Program, section chief, Breast Medical Oncology, The Ohio State University Comprehensive Cancer Center–James, director, Medical Oncology Fellowship Program in Breast Cancer, The Ohio State College of Medicine, discusses determining treatment courses for individual patients with HER2-positive breast cancer.

In general, patients with HER2-positive breast cancer will receive trastuzumab (Herceptin) in combination with pertuzumab (Perjeta) and taxane-based chemotherapy as frontline therapy, says Ramaswamy. Most patients will receive ado-trastuzumab emtansine (T-DM1; Kadcyla) as second-line therapy, Ramaswamy explains. This sequence of therapy is based on the strong overall survival data observed with the regimens in clinical trials, Ramaswamy says. 

However, in the third-line and beyond settings, patient factors should be considered to guide treatment selection, says Ramaswamy. For example, a patient with significant central nervous system involvement may be better suited for tucatinib (Tukysa) compared with a patient who has cardiac problems, who could be considered for neratinib (Nerlynx) plus capecitabine, Ramaswamy explains.

Additionally, some patients may not want to take an oral medication, so intravenous options, such as fam-trastuzumab deruxtecan (Enhertu) or margetuximab-cmkb (Margenza) plus chemotherapy, could be considered, says Ramaswamy. Clinical trials could also offer options for patients during any line of treatment to determine whether newer therapies should be included in the therapeutic armamentarium, concludes Ramamswamy.

Bhuvaneswari Ramaswamy, MD, discusses determining treatment courses for individual patients with HER2-positive breast cancer.  



Dr. Ramaswamy on Determining Treatment Courses in Metastatic HER2+ Breast Cancer 

Bhuvaneswari Ramaswamy, MD, member, Translational Therapeutics Program, section chief, Breast Medical Oncology, The Ohio State University Comprehensive Cancer Center–James, director, Medical Oncology Fellowship Program in Breast Cancer, The Ohio State College of Medicine, discusses the potential utility of CDK4/6 inhibitors in the adjuvant setting for patients with hormone receptor (HR)–positive, HER2-negative breast cancer.

The phase 3 monarchE trial (NCT03155997) yielded the first positive findings showing that a CDK4/6 inhibitor improved invasive disease-free survival (iDFS) when combined with endocrine therapy as adjuvant treatment for patients with high-risk, early-stage HR-positive/HER2-negative breast cancer. Other studies, such as the PALLAS (NCT02513394) and PENELOPE-B (NCT01864746) trials, failed to demonstrate an iDFS benefit with the addition of a CDK4/6 inhibitor to adjuvant endocrine therapy compared with endocrine therapy alone in this patient population, Ramaswamy says.

Based on these findings, patients with high-risk early-stage breast cancer appear to be the target population for adjuvant CDK4/6 inhibition because these patients tend to have micrometastatic disease, Ramaswamy says. Although longer-term follow-up from the monarchE trial is needed to demonstrate the durability of these responses, CDK4/6 inhibition could have utility in the adjuvant setting for a properly selected patient population, concludes Ramaswamy.

Bhuvaneswari Ramaswamy, MD, discusses the potential utility of CDK4/6 inhibitors in the adjuvant setting for patients with hormone receptor–positive, HER2-negative breast cancer.  



Bhuvaneswari Ramaswamy, MD

Articles

Dr. Ramaswamy on the Real-World Data Implications of Palbociclib in HR-Positive Breast Cancer

Dr. Ramaswamy on Determining Treatment Courses in Metastatic HER2+ Breast Cancer

Dr. Ramaswamy on the Potential for Adjuvant CDK4/6 Inhibition in HR+/HER2- Breast Cancer