Dr Gandhi on Considerations for Continuing CDK4/6 Inhibitors After Progression in HR+ Advanced Breast Cancer

Shipra Gandhi, MD, assistant professor, oncology, Breast and Early Phase Clinical Trials, Department of Medicine, Roswell Park Comprehensive Cancer Center, discusses considerations for continuing treatment with a CDK4/6 inhibitor following disease progression in patients with hormone receptor (HR)–positive advanced breast cancer.

Clinical trials evaluating the continuation of CDK4/6 inhibition following progression in this patient population have generated inconsistent results, Gandhi begins. Findings from the phase 2 PALMIRA (NCT03809988) and PACE (NCT03147287), which each investigated continuing palbociclib (Ibrance)-based therapy after initial progression on palbociclib plus endocrine therapy, and these studies did not show an improvement in progression-free survival (PFS), she says.

 (NCT02632045), showed that switching to ribociclib (Kisqali) following progression on a prior CDK4/6 inhibitor led to a statistically significant improvement in PFS. Furthermore, data from 

 (NCT05169567) demonstrated that abemaciclib (Verzenio) plus fulvestrant (Faslodex) improved PFS vs placebo plus fulvestrant after progression, Gandhi explains.

When subgroup analyses were completed for MAINTAIN and postMONARCH, findings indicated that most of the benefit was observed in patients with endocrine-sensitive disease and those who did not have visceral disease, Gandhi continues. She elaborates that endocrine-sensitive disease is defined as prior treatment with a CDK4/6 inhibitor for over 1 year.

Based on the available data, Gandhi explains that she would consider continuing with a CDK4/6 inhibitor after progression in patients with endocrine-sensitive disease and in patients who do not have visceral metastases. She also notes that she would consider this approach for patients who do not have have targetable mutations.

In patients whose disease harbors targetable mutation or those with endocrine-resistant switching therapies following progression on a CDK4/6 inhibitor–based regimen should be considered, Gandhi concludes.

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Shipra Gandhi, MD, discusses considerations for continuing with a CDK4/6 inhibitor or switching therapies in HER2- negative advanced breast cancer.

Addressing socioeconomic health disparities has been a crucial objective of health policy in the United States. The relationship between cancer incidence and mortality and socioeconomic status varies across malignancies.

Risk factors associated with the development and progression of cancer, such as smoking, alcohol use, dietary habits, obesity, lifestyle choices, environmental pollution, and occupational exposure, are directly and indirectly influenced by an individual’s socioeconomic status and where they live. Although existing data indicate a higher incidence of breast cancer among those with higher socioeconomic status, limited information is available regarding the clinical outcomes of breast cancer based on neighborhood socioeconomic status.

Our research group at Roswell Park Comprehensive Cancer Center sought to clarify these possible connections. What we have found from our analysis of nationwide data underscores how imperative it is for clinicians to examine the relationship between neighborhood socioeconomic status and morbidity and mortality rates of specific malignancies.

Socioeconomic inequalities in cancer mortality are a global concern. Insufficient resources in areas with lower socioeconomic status contribute to delayed cancer diagnoses and inadequate treatment options, resulting in significant mortality and morbidity.

 Social factors, including income, educational and job opportunities, housing, social support, transportation barriers, and racial disparities also play a significant role in cancer-related mortality. These disparities are particularly pronounced in low- and middle-income countries where access to care and financial toxicity pose challenges for the majority of patients. Because of disparities in socioeconomic factors and developmental infrastructure, areas characterized by low individual and neighborhood socioeconomic status may be associated with poorer prognosis for certain malignancies.

Breast cancer is the most prevalent form of malignancy among women worldwide.

 Survival rates for patients with breast cancer are influenced by demographic, clinical, and pathologic factors. Additionally, racial and ethnic backgrounds as well as socioeconomic factors have been shown to effect clinical outcomes in breast cancer.

Using information compiled through the national cancer database, we conducted an analysis to explore the effect of neighborhood deprivation on clinical outcomes in breast cancer. Our findings were based on data from 88,572 patients throughout the US and revealed a higher prevalence of racial and ethnic minorities, particularly among individuals identifying as Black/African American or as Hispanic/Latinx, in areas characterized by greater deprivation compared with those not characterized as deprived. Likewise, the most deprived areas had a higher proportion of uninsured patients.

We observed predominant levels of aggressive subtypes of breast cancer, including HER2-positive and triple-negative breast cancer, as well as advanced disease stages, in the most deprived neighborhoods. Our analyses demonstrate that patients with early-stage breast cancer from areas with greater neighborhood deprivation experienced inferior overall and breast cancer-specific survival rates,

 after adjustment for common confounders effecting survival. Our findings were presented as a Poster Spotlight Discussion at the 2022 San Antonio Breast Cancer Symposium.

The identification of higher breast cancer stages in areas with the highest levels of deprivation raises concerns about delayed access to screening, insufficient insurance support, and inadequate education and awareness regarding general health among individuals residing in socioeconomically disadvantaged areas. Early detection of breast cancer is associated with improved prognosis, provided that appropriate care is delivered. Although our study results revealed a higher proportion of individuals representing racial and ethnic minorities in economically deprived neighborhoods, the disparity in survival rates persisted even after adjusting for patients’ race, ethnicity, and clinicopathological features. This highlights the significant role that both patients’ socioeconomic status and neighborhood characteristics play in determining breast cancer outcomes.

Our study findings have elucidated the critical effect of neighborhood deprivation on survival outcomes of patients with breast cancer. The cumulative impact of various neighborhood factors, such as infrastructure (eg, schools and hospitals), accessibility to nearby health care facilities, availability of healthy food and water, and neighborhood hygiene contributes to this phenomenon. Factors such as prolonged exposure to water and air pollution in underresourced neighborhoods can induce changes in the tumor microenvironment of individuals residing in those areas, potentially leading to the development of aggressive forms of breast cancer.

Unfavorable neighborhood conditions also can contribute to the emergence of chronic medical comorbidities, fostering an immunosuppressive tumor microenvironment that facilitates the development and progression of breast cancer.

Our work outlines strategies that can be implemented to effectively address these disparities as follows:

Enhance coordination among social workers and case managers at hospitals to identify and address barriers preventing patients from underresourced neighborhoods from accessing necessary care.

Implement government policies aimed at improving basic infrastructure in underresourced neighborhoods.

Deploy mobile mammography units to reach neighborhoods with limited access to health care, facilitating proper disease screening.

Provide free transportation services for patients residing in underresourced neighborhoods, ensuring their ability to attend regular appointments, receive treatment, and undergo necessary scans or radiation therapy.

Provide financial aid and support to patients with breast cancer from the most deprived neighborhoods and their families.

Implement community-based education and awareness programs in underresourced neighborhoods, focusing on breast cancer prevention, early detection, and the importance of regular screenings. These programs can be conducted in collaboration with local community organizations, schools, and health care providers to ensure widespread dissemination of information and empower individuals with knowledge to make informed decisions about their health.

Establish partnerships with local businesses and organizations to provide financial incentives and resources for breast cancer screenings and treatment in underresourced neighborhoods. Collaborating with community stakeholders, such as pharmacies, clinics, and charitable organizations, can help alleviate the financial burden associated with screenings and treatments. Such measures can involve offering discounted or subsidized mammograms, treatment medications, and supportive care services, as well as facilitating access to patient assistance programs or grants for individuals from disadvantaged backgrounds.

It is crucial for cancer clinicians to identify patients seeking breast cancer treatment from areas characterized by higher deprivation indices. This key step enables the implementation of strategies aimed at overcoming barriers related to financial status and transportation, thereby facilitating patients’ access to essential care, regular appointments, and vital diagnostic procedures, treatments, and follow-ups. These interventions hold significant potential to improve the clinical outcomes for patients with breast cancer.

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Shipra Gandhi, MD

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