Breast Cancer New Nemeses: CDK4/6 Inhibitors Rave Against Recurrence, But Have They Crashed the EBC Party in NATALEE & monarchE Real-World Dance-Off? @PTarantinoMD Transcript: https://t.co/aOZ6mZDWym @DrHopeRugo @DrDennisSlamon @SABCSSanAntonio @AACR #SABCS24 #BreastCancer,… pic.twitter.com/40BWq28tDZ
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Advancements in Early Breast Cancer Treatment with CDK4/6 Inhibitors
Paolo Tarantino, an oncology expert, has shed light on the transformative impact of CDK4/6 inhibitors in the treatment of hormone receptor-positive, HER2-negative breast cancer.
Expanded Treatment Scope:
Initially, only abemaciclib was available for those with high-risk disease, defined by significant lymph node involvement. However, with the approval of ribociclib, the scope has widened. “This allows us to address a large population of patients, about one-third of all those with hormone receptor-positive early-stage disease,” states Tarantino. Ribociclib’s broader approval now includes patients with any node-positive disease or those with node-negative but high-risk cancer, like grade three or genomically selected cases.
Long-term Efficacy and Safety:
The medical community has been keen to understand if these inhibitors are curative or merely delay recurrence. “The major question in our minds has been, are we curing, or are we delaying recurrence?” Tarantino reflects. The Penelope B trial with palbociclib indicated increased recurrence post-treatment, but newer data from the monarchE and NATALEE trials with abemaciclib and ribociclib respectively, show no such increase. Instead, there’s evidence of an ongoing benefit even after discontinuation, hinting at the potential elimination of micrometastatic disease.
Statistical Insights:
Analyzing trial data across various subgroups can be statistically complex, yet Tarantino notes, “The trend in all these populations shows ribociclib providing benefit, with a 25-35% reduction in recurrence risk.” This supports the drug’s use despite challenges in pinpointing statistical significance in every subgroup.
Side Effect Profile:
The NATALEE trial used a lower dose of ribociclib, which contributed to a favorable side effect profile. “Ribociclib seemed to be well tolerated,” Tarantino confirms, highlighting reduced rates of severe side effects and manageable issues like hepatic toxicity and QTc interval changes.
Real-World Application:
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- Eligibility and Outcomes: Real-world data from the Flatiron database, involving over 7,500 patients, revealed that 15% would qualify for abemaciclib under monarchE criteria, while 33% would fit ribociclib’s NATALEE criteria. The data underscores a stark reality with 20-30% expected recurrence rates within five years among these groups, reinforcing the need for effective adjuvant strategies.
Conclusion: The introduction of CDK4/6 inhibitors has been a significant step forward in managing recurrence in early breast cancer. Tarantino emphasizes, “We need to utilize all the tools available to optimize outcomes for these patients.” Ongoing research into biomarkers aims to further personalize this treatment, ensuring it reaches those who will benefit most.