Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.
“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”
The study results were presented at the annual meeting of the American Society of Clinical Oncology.
Black Women Underrepresented
Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”
In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.
The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).
Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.
The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.
Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.