The use of CDK4/6 inhibitors remains pivotal in treating hormone receptor (HR)-positive metastatic breast cancer, both HER2-negative and HER2-positive, especially for patients experiencing visceral crisis. Dr. Neelam V. Desai, a medical oncologist at Atrium Health Levine Cancer Institute in Matthews, North Carolina, emphasized the importance of these inhibitors during a recent interview. “We currently use CDK4/6 inhibitors with endocrine therapy in the first line for patients with visceral crisis. Right now, the data is strong for ribociclib [Kisqali],” she stated, underscoring the ongoing relevance of these therapies.
For patients not in visceral crisis, Dr. Desai noted that the choice among the three FDA-approved CDK4/6 inhibitors—ribociclib, palbociclib [Ibrance], and abemaciclib [Verzenio]—is based on established study data. In particular, she highlighted the role of palbociclib during the maintenance phase for patients diagnosed with HR-positive, HER2-positive metastatic breast cancer.
Clinical Trials and Emerging Data
Dr. Desai discussed several key trials that have shaped the current understanding of CDK4/6 inhibitors for treating metastatic HR-positive breast cancer. These include the phase 3 PALOMA-2 trial, the phase 2 PARSIFAL trial, and the Young-PEARL trial, which evaluate palbociclib. The MONALEESA trials assess ribociclib, while the phase 3 MONARCH 3 trial focuses on abemaciclib. All these studies consistently demonstrate improvements in progression-free survival (PFS).
Although the ribociclib trials report a statistically significant improvement in overall survival (OS), the MONARCH 3 trial did not meet statistical significance for its OS endpoint, despite showing a clinically meaningful benefit of 13.1 months. “The palbociclib trials also did not show statistically significant improvements in OS, but real-world studies indicate better outcomes,” Dr. Desai explained, highlighting the complexities surrounding data collection and interpretation in clinical trials.
When selecting a CDK4/6 inhibitor, Dr. Desai considers patient-specific factors such as age, comorbidities, and treatment tolerability. While she generally prefers ribociclib and abemaciclib due to their OS benefits, she often opts for palbociclib for older patients who may face challenges in tolerating the side effects associated with abemaciclib, such as diarrhea and fatigue.
Advancements in HER2-Positive Metastatic Breast Cancer Treatment
Recent data from the phase 3 PATINA trial, presented at the 2024 San Antonio Breast Cancer Symposium, further enhance the understanding of treatment for HR-positive, HER2-positive metastatic breast cancer. The current standard of care for these patients involves induction taxane, trastuzumab [Herceptin], and pertuzumab [Perjeta]. After six to eight cycles, the taxane is discontinued, and patients continue with trastuzumab and pertuzumab, supplemented by endocrine therapy for those with HR-positive disease.
The PATINA trial evaluated the addition of palbociclib to this regimen. Results indicated that incorporating palbociclib led to a substantial 15.2-month improvement in PFS. While OS data from this trial are not yet mature, Dr. Desai expressed optimism about the findings. “I would certainly consider adding palbociclib to maintenance approaches for patients who have HR-positive, HER2-positive metastatic disease,” she stated.
Dr. Desai noted that palbociclib is generally well tolerated, with the trial showing no alarming adverse effects or new safety signals when combined with trastuzumab and pertuzumab. She emphasized the importance of managing receptor signaling, stating, “There is a lot of crosstalk in receptor signaling. It’s important to monitor long-term data, as managing both HR and HER2 signaling is crucial for preventing disease progression.”
The RIGHT Choice trial evaluated the use of ribociclib in combination with endocrine therapy for patients with HR-positive, HER2-negative metastatic disease, particularly those at visceral crisis. This study compared the ribociclib regimen against a doublet chemotherapy approach and demonstrated significant improvements in PFS with fewer adverse effects.
As CDK4/6 inhibitors continue to evolve in the landscape of breast cancer treatment, ongoing trials and emerging data will likely inform clinical practices and improve patient outcomes. Dr. Desai’s insights underline the critical role of these therapies in the first-line treatment of metastatic breast cancer, showcasing how tailored approaches can enhance care for a diverse patient population.
