One of the important things in these studies is the need for very long-term follow-up. Even with stage I breast cancer, we’re seeing 14% of patients with recurrent disease after 5 years of adjuvant endocrine therapy and [risk of recurrence] up to 20 years. That can rise to 50% in patients who have higher-risk multi-node breast cancer. Could we use CDK4/6 inhibitors to “nip the disease in the bud,” so you don’t have dormancy and late recurrences? That will be fascinating to see as we look at these trials over time. It’s also going to be important to evaluate quality of life and make sure that we’re not making everybody exhausted for all those years. Identifying the patients who are most likely to benefit will be critical.
The NATALEE trial, which is supposed to open later this year, will use 3 years of a CDK4/6 inhibitor; this is the adjuvant trial with ribociclib. Three years is a long time, so it will be interesting to see what the compliance is with longer durations. We’ve found that even 2 years is a long time in the adjuvant setting, although many people with high-risk disease will stick with it.
What other pathway blockades are being investigated?
Along with CDK4/6 inhibitors, there’s a great desire to look at other pathways to block. There are many different studies ongoing looking at HDAC inhibitors, early-phase trials of FGFR inhibitors, and other agents of great interest. IPATunity 130 is a trial with the AKT inhibitor ipatasertib in both ER-positive and triple-negative breast cancer. The trial is targeting patients whose tumors have disordered AKT-PI3K or PTEN
tumor suppressor gene.
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