CDK 4/6 Inhibitors Show Efficacy in HR+ MBC With ESR1 Mutations

Jamie Brett, resident in internal medicine at Massachusetts General Hospital, discusses the effectiveness of CDK4/6 for patients with hormone receptor-positive metastatic breast cancer (MBC) with ESR1 mutations and fusions.

Within a presentation at the AACR Annual Meeting 2022, Brett evaluated patients with MBC who started on a CDK4/6 inhibitor within 30 days of ctDNA testing and analyzed their time-to-next-treatment data.

Findings revealed there to be no significant difference in time to next treatment between those with ESR1 fusions and wild type status. While future studies plan to expand this research, this trial showed those with ESR1 mutations to have shorter overall survival (HR, 0.58; 95% CI, 0.42 - 0.82, P =0.002).

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0:08 | We used our own MGH database to look for patients with ESR1 fusions. What we found is that in the real-world setting, CDK 4/6 inhibitors can be useful patients with ESR1 mutations. In fact, these patients do very similarly in terms of time to next treatment as patients with ESR1 wild type status. CDK 4/6 inhibitors also seem to be beneficial in each of the cases that we found of patients with ESR1 fusions.

0:35 | The summary result is that in the real-world setting, CDK 4/6 inhibitors seem to be a useful strategy of therapy for patients with ESR1 alterations that are otherwise very hard to treat because of endocrine resistance. There's a lot of future directions that I think include expanding the ESR1 fusion case series to include a lot more patients. They're looking into the garden data in terms of which patients really do well with CDK 4/6 inhibitors and which patients do not do well, and why there's still some differences in survival long term with these patients despite similar outcomes in terms of time to next treatment on CDK 4/6 inhibitors.