
Editor's Note: At the 2024 San Antonio Breast Cancer Symposium (SABCS), a study led by Professor Noor Wortelboer from Erasmus University Medical Center in Rotterdam was presented during the "Poster Spotlight 2: Personalizing CDK 4/6 Inhibitor Therapy for Patients with Metastatic Breast Cancer: Survival, QOL, and Biomarkers" session. This research, based on the SONIA trial data, provided an in-depth analysis of health-related quality of life (HRQoL) outcomes in patients using CDK4/6 inhibitors (CDK4/6i) at different treatment lines. The findings offer crucial insights into how CDK4/6i impacts patients’ quality of life and serve as valuable guidance for optimizing treatment strategies in advanced breast cancer. Oncology Frontier invited Dr. Yan Xue from Xi’an International Medical Center Oncology Hospital to interpret and comment on the study's data.
Study Title:
PS2-04 — Health-Related Quality of Life with First- vs. Second-Line Use of CDK4/6 Inhibitors in Advanced Breast Cancer: Results from the Phase III SONIA Trial (BOOG 2017-03)
Dr. Yan Xue:With ongoing advancements in breast cancer treatment, CDK4/6 inhibitors have become a cornerstone in managing ER+/HER2- advanced breast cancer. However, the optimal timing for initiating CDK4/6i therapy remains a topic of debate. At this year’s SABCS, Noor Wortelboer and colleagues presented data from the Phase III SONIA trial, comparing HRQoL outcomes between first-line and second-line use of CDK4/6i.
The SONIA trial, a randomized controlled study, enrolled 1,050 patients to compare the efficacy and safety of first-line versus second-line CDK4/6i combined with different endocrine therapies in HR+/HER2- advanced breast cancer. Previous reports showed no significant difference in second progression-free survival (PFS2) between the two strategies. However, first-line CDK4/6i use was associated with more adverse effects and higher costs. This analysis focused on the HRQoL outcomes under these two treatment approaches.
The study utilized the Functional Assessment of Cancer Therapy–Breast (FACT-B) questionnaire to evaluate HRQoL, covering physical, social, emotional, functional well-being, and breast cancer-specific domains. Results indicated that there was no significant difference in total FACT-B scores or subscale scores between patients receiving CDK4/6i as first-line or second-line therapy. Additionally, no interaction between treatment timing and time trends was observed. This suggests that patients’ HRQoL remains similar regardless of whether CDK4/6i is used in the first or second line of therapy.
Clinical Implications:This finding holds significant clinical relevance. First, it suggests that delaying CDK4/6i therapy until the second line does not compromise HRQoL, offering a more cost-effective and potentially less toxic treatment strategy. Second, these results support personalized treatment approaches in clinical practice. Physicians can make flexible treatment decisions based on individual patient conditions and preferences to optimize therapeutic outcomes and quality of life.
Study Limitations:However, the study has some limitations. Despite a high questionnaire completion rate, some patients missed assessments at certain time points due to various reasons, potentially affecting the accuracy of the results. Moreover, HRQoL is a subjective measure influenced by multiple factors, such as psychological state and social support, which were not fully accounted for in the study.
Additionally, 91% of first-line patients in the trial received palbociclib, which lacks overall survival (OS) benefits, limiting the findings’ applicability to other CDK4/6i drugs like ribociclib and abemaciclib. Furthermore, fulvestrant used in the second line may not be the most suitable comparator. With the ongoing development of new therapies, second-line treatment options now include fulvestrant combined with alpelisib or capivasertib, PARP inhibitors for patients with gBRCA1/2 mutations, and antibody-drug conjugates (ADCs) like T-DXd and sacituzumab govitecan.
In China, since the 2017 implementation of dynamic adjustments to the national medical insurance catalog, various CDK4/6 inhibitors, including ribociclib, abemaciclib, and palbociclib, have been included in the reimbursement list, significantly easing the financial burden on patients. Moving forward, more comprehensive research is needed to determine the optimal timing and approach for CDK4/6i use in advanced breast cancer.
Dr. Yan Xue
- Chief Physician, PhD, Master’s Supervisor
- Vice President, Xi’an International Medical Center Oncology Hospital
- Director, Department of Oncology I
- Vice Chair, Breast Disease Expert Committee, China Health Promotion Foundation
- Vice Chair, Breast Disease Branch, Chinese Society of Sexology
- Standing Member, Integrative Breast Cancer Committee, Chinese Anti-Cancer Association
- Member, Tumor Clinical Chemotherapy Committee, Chinese Anti-Cancer Association
- Member, Breast Cancer Expert Committee, Chinese Society of Clinical Oncology (CSCO)
- Member, Geriatric Oncology Prevention and Treatment Expert Committee, CSCO
- Member, Oncology Professional Committee, Chinese Research Hospital Association
- Member, Oncology Rehabilitation and Supportive Care Group, Chinese Medical Association