Recent developments in the treatment of hormone receptor-positive (HR+) metastatic breast cancer have underscored the critical role of CDK4/6 inhibitors. These drugs are now a cornerstone of first-line therapy for both HR-positive, HER2-negative and HR-positive, HER2-positive metastatic breast cancer, particularly for patients experiencing visceral crisis. Dr. Neelam V. Desai, a medical oncologist at the Atrium Health Levine Cancer Institute in Matthews, North Carolina, provided insights on this topic during an interview with OncLive®.
Dr. Desai noted the current reliance on CDK4/6 inhibitors combined with endocrine therapy for patients in visceral crisis, emphasizing that data favors the use of ribociclib (Kisqali) in these cases. For patients not in visceral crisis, she stated that clinicians can choose among the three approved CDK4/6 inhibitors—ribociclib, palbociclib (Ibrance), and abemaciclib (Verzenio)—based on established clinical trial data. In particular, she highlighted how adding palbociclib during the maintenance phase can be advantageous for patients with HR-positive, HER2-positive metastatic breast cancer.
Key Clinical Trials and Insights
Dr. Desai discussed pivotal clinical trials that have evaluated the efficacy of the three FDA-approved CDK4/6 inhibitors in metastatic HR-positive, HER2-negative breast cancer. These include the phase 3 PALOMA-2 trial (NCT01740427) for palbociclib, the phase 2 PARSIFAL trial (NCT02491983), and the phase 2 Young-PEARL trial (NCT02592746). She also referenced the MONALEESA trials for ribociclib and the phase 3 MONARCH 3 trial (NCT02246621) for abemaciclib.
All these trials consistently indicated an improvement in progression-free survival (PFS). Notably, ribociclib trials demonstrated a statistically significant improvement in overall survival (OS). Although the MONARCH 3 trial did not achieve statistical significance for its OS endpoint, the reported benefit of 13.1 months was deemed clinically meaningful. Similarly, while the palbociclib trials showed no statistically significant improvement in OS, concerns about data collection methods in these studies suggest that some real-world evidence indicates improvements in both PFS and OS.
Dr. Desai maintains that all three CDK4/6 inhibitors should be considered in the treatment of metastatic breast cancer, particularly in the first or second line. Her decision-making process is influenced by the patient’s age, comorbidities, and ability to tolerate potential adverse effects. She expressed a preference for ribociclib and abemaciclib due to their OS benefits but considers palbociclib a suitable choice for older patients or those with multiple health issues.
Emerging Data from Recent Trials
The upcoming 2024 San Antonio Breast Cancer Symposium will feature data from the phase 3 PATINA trial (NCT02947685), which included patients with HR-positive, HER2-positive metastatic breast cancer. The current standard of care involves treating these patients with induction taxane, trastuzumab (Herceptin), and pertuzumab (Perjeta). After six to eight cycles, the taxane is discontinued, and endocrine therapy is initiated for those with HR-positive disease.
In the PATINA trial, patients undergoing maintenance therapy were randomly assigned to receive trastuzumab and pertuzumab with or without palbociclib. Early results indicated a significant 15.2-month improvement in PFS for those receiving the combination therapy, although OS data is still pending. Dr. Desai remarked that the addition of palbociclib did not introduce significant adverse effects and did not reveal any new safety signals, suggesting it is a viable option in clinical practice.
Dr. Desai emphasized the importance of addressing both HR and HER2 signaling pathways in treatment. She acknowledged that while HR signaling is crucial, HER2 receptor activity often raises concerns about cancer progression. Therefore, a dual approach targeting both pathways is vital for effective management.
The RIGHT Choice trial further examined the efficacy of first-line ribociclib and endocrine therapy compared to traditional chemotherapy regimens in patients with HR-positive, HER2-negative metastatic disease or visceral crisis. Results indicated that the ribociclib and endocrine therapy combination led to improvements in PFS with fewer adverse effects.
As the landscape of breast cancer treatment continues to evolve, ongoing trials and emerging data are expected to refine therapeutic strategies further and enhance patient outcomes. The insights from Dr. Desai and her colleagues will play a pivotal role in shaping future approaches to managing this challenging disease.
