The use of CDK4/6 inhibitors remains pivotal in the treatment of hormone receptor (HR)–positive metastatic breast cancer, according to Dr. Neelam V. Desai, a medical oncologist at the Atrium Health Levine Cancer Institute. These medications are particularly critical for patients experiencing visceral crisis in both HR-positive, HER2-negative and HR-positive, HER2-positive cases. Dr. Desai emphasized that current data strongly supports the use of ribociclib (Kisqali) in these scenarios.
In an interview with OncLive®, Dr. Desai stated, “We currently use CDK4/6 inhibitors with endocrine therapy in the first line for patients with visceral crisis.” For patients not in visceral crisis, she noted the choice between the three approved CDK4/6 inhibitors depends on findings from established studies. She also highlighted the importance of palbociclib (Ibrance) during the maintenance phase for HR-positive, HER2-positive metastatic breast cancer patients.
Dr. Desai elaborated on various clinical trials that have evaluated the three FDA-approved CDK4/6 inhibitors, providing insights into their effectiveness. Key studies include the PALOMA-2 trial (NCT01740427) for palbociclib, the MONALEESA trials for ribociclib, and the MONARCH 3 trial (NCT02246621) for abemaciclib (Verzenio). Each of these trials consistently demonstrated an improvement in progression-free survival (PFS), with ribociclib trials also revealing a statistically significant increase in overall survival (OS).
While the MONARCH 3 trial did not meet its OS endpoint for statistical significance, it still indicated a clinically meaningful benefit of 13.1 months. Critically, the palbociclib trials did not show statistically significant OS improvements, though some real-world studies suggest better outcomes.
In selecting a CDK4/6 inhibitor, Dr. Desai considers various patient factors, including age, comorbidities, and treatment tolerability. “I tend to prefer ribociclib and abemaciclib because of the OS benefit; however, I keep palbociclib as an option for my older patients,” she said. This approach takes into account potential adverse effects, particularly for patients with multiple health issues.
Advancements were also discussed regarding the PATINA trial (NCT02947685), which was presented at the 2024 San Antonio Breast Cancer Symposium. This trial involved patients with HR-positive, HER2-positive metastatic breast cancer receiving induction therapy with taxane, trastuzumab (Herceptin), and pertuzumab (Perjeta). Following six to eight cycles of taxane treatment, patients were randomly assigned to maintain their regimen with or without palbociclib. The results indicated a significant improvement in PFS by 15.2 months with the addition of palbociclib.
Dr. Desai noted that the OS data from this trial are still maturing but expressed confidence in the compelling nature of the findings. “Generally, palbociclib is well tolerated,” she remarked, adding that the combination with trastuzumab and pertuzumab did not lead to significant adverse effects.
The complexity of receptor signaling in breast cancer treatment is also a crucial aspect. Dr. Desai emphasized the importance of addressing both HR and HER2 receptor pathways to manage disease progression effectively. The RIGHT Choice trial also explored the combination of ribociclib and endocrine therapy for HR-positive, HER2-negative metastatic disease, demonstrating improved PFS with fewer adverse effects compared to traditional chemotherapy regimens.
As ongoing research continues to refine treatment strategies, Dr. Desai’s insights underline the importance of tailored approaches that consider patient-specific factors and the evolving landscape of breast cancer therapy. The integration of CDK4/6 inhibitors into standard treatment protocols reflects a significant advancement in managing HR-positive metastatic breast cancer, offering hope for improved patient outcomes.