Secondary objectives included frequency of targetable mutations, accuracy of ctDNA testing (to be reported later), and others.
Results showed that ESR1 mutations were most common within the original population (27.7%), followed by AKT1 mutations (4.2%) and HER2 mutations (2.7%). In the treatment cohort, more than half of the patients had a HER2 mutation (58%) and/or an AKT1 mutation (54%), whereas a smaller proportion had an ESR1 mutation (38%). Approximately two-thirds of patients (64%) had hormone receptor–positive, HER2-negative breast cancer; 17% had triple-negative breast cancer; 6% had hormone receptor–positive, HER2-positive disease; 3% had hormone receptor–negative, HER2-positive disease; and 9% had other/unknown phenotypes. Approximately two-thirds of patients (65%) had received at least two lines of prior therapy for advanced disease.
For patients with an ESR1 mutation treated with extended-dose fulvestrant (cohort A) only 8.1% achieved a response, which was below the threshold for inferred efficacy. For patients with a HER2 mutation treated with neratinib with or without fulvestrant (cohort B), 25.0% had a response, thereby demonstrating inferred efficacy. Efficacy was also inferred in patients with an AKT1 mutation treated with capivasertib plus fulvestrant (cohort C), as 22.2% of these patients had a response. In the AKT basket (cohort D), 10.5% of patients had a response, which fell below the efficacy threshold; however, an exploratory analysis of this cohort showed that patients with an AKT1 mutation had a response rate of 33.3% (two out of six patients), which did meet efficacy criteria.
Adverse events were consistent with previous reports. The investigators noted that extended-dose fulvestrant was well tolerated.
“In conclusion, we show that circulating tumor DNA testing offers a simple, efficient and relatively fast method of tumor genotyping,” Dr. Turner said.
The investigators disclosed relationships with Puma Biotechnology, AstraZeneca, Guardant Health, and Bio-Rad.
SOURCE: Turner et al. SABCS. 2019 Dec 12. Abstract GS3-06.