Oral SERD Promising in ER-Positive Breast Cancer With ESR1 Mutations
The investigational third-generation nonsteroidal oral selective estrogen receptor degrader RAD1901 was associated with a 23% objective response rate among 40 heavily pretreated women with estrogen receptor (ER)-positive, HER2-negative breast cancer.
The investigational third-generation nonsteroidal oral selective estrogen receptor degrader (SERD) RAD1901 was associated with a 23% objective response rate among 40 heavily pretreated women with estrogen receptor (ER)-positive, HER2-negative breast cancer, according to authors of a phase I dose-escalation and safety cohort study (NCT02338349) presented (abstract 1014) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.
“RAD1901 has demonstrated evidence of single-agent activity, with confirmed partial responses in heavily pretreated patients with advanced ER-positive breast cancer, including those with ESR1 mutations, warranting additional clinical development,” reported Aditya Bardia, MD, MPH, of Massachusetts General Hospital Cancer Center and Harvard Medical School in Boston.
In preclinical studies, RAD1901 exhibited dose-dependent degradation of estrogen receptors and ER pathway genes, and antitumor activity, Bardia reported.
Earlier work also suggested that SERD agents might exhibit enhanced activity against tumors that harbor ESR1 mutations. How best to classify ESR1 mutations in breast cancer has yet to be resolved. In this study, the researchers used circulating tumor DNA (ctDNA) to determine if tumors harbored ESR1 mutations.
Study participants were “heavily pretreated,” with a median of 3 prior treatment lines, Bardia noted.
The clinical benefit rate at 24 weeks was 42% overall and higher among patients with ESR1 mutation-positive disease (10 of 19 such patients saw clinical benefit, compared to 5 of 18 patients with ESR1-negative disease).
The recommended dose of RAD1901 is 400 mg daily, the researchers concluded. Median progression-free survival was 4.5 months among patients receiving that dose schedule. Of the 40 participants, 15 were still on study at the time of analysis.
“RAD1901 was generally well-tolerated, with the most common adverse events being low-grade nausea and dyspepsia,” Bardia noted. No grade 3 or 4 nausea or dyspepsia were noted.
