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Racial Disparities in Access to PI3K Inhibitors Despite Comparable Mutation Burden: Addressing Data Gaps in Early-Onset and Rare Cancers
1 PhD Scholar, Faculty of medical biochemistry, Adichunchanagiri University, B G Nagara, India. 2 Professor and Head, Department of biochemistry, BGS Medical College and Hospital Nagnur, Adichunchanagiri University, India.
Published Online: January-April 2026
Pages: 01-07
Precision oncology promises tailored treatment by focusing on the genome; however, racial disparities in access to PI3K inhibitors persist, despite the mutation burden being comparable across racial and ethnic groups. Around 30– 50% of solid tumors have changes in the PI3K pathway, such as PIK3CA hotspot mutations, PTEN loss, and AKT1 activations. However, large genomic databases like The Cancer Genome Atlas (TCGA) and MSK-IMPACTdid not have any information on how common these changes are by race or ethnicity.But real-world data show that Black and Hispanic patients are given these inhibitors much less often. This is a problem because there aren't enough data on early-onset cancers (diagnosed at ≤50 years) and rare cancers .The primary cohort had been administered PI3K inhibitors (alpelisib or investigational agents for trial follow-up) within 90 days of the detection of PI3K pathway alteration.We used multivariable logistic regression models to look at differences by race/ethnicity (White, Black, Hispanic, Asian, Other) and by age of onset and the rarity of cancer (NCI rare cancer designations). Covariates included insurance status, Eastern Cooperative Oncology Group (ECOG) performance status, line of therapy, histology, and socioeconomic indicators. Sensitivity analyses looked at different types of mutations (PIK3CA hotspots vs. other changes), where the practice took place (in an academic setting vs. a community setting), and where in the world it took place. A total of 14,293 patients identified abnormalities in the PI3K pathway (31.2%; PIK3CA 72%, PTEN 18%, AKT1 6%, and 4% from other sources), with mutations showing statistical consistency across racial groups (White 31.5%, Black 30.8%, Hispanic 29.9%, Asian 32.1%, Other 30.4%; P=0.42). Overall, the use of PI3K inhibitors was low (8.2% n=1,172), but there were differences: Black patients were 42% less likely to receive them (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.45- 0.74; P<0.001), Hispanic patients were 35% less likely (OR 0.65; 95% CI 0.49-0.86; P=0.003), and Asian patients were 28% less likely (OR 0.72; 95% CI 0.52-0.99; P=0.045) than White patients. These differences were still there after adjusting for all individuals (aOR of Black 0.62; 95% CI 0.48-0.80; P<0.001).In the early-onset subgroup (n=4,821; age ≤50; 42% PI3K-modified), disparities were heightened (Black aOR 0.49; 95% CI 0.32-0.75; P=0.001; Hispanic aO0.54; 95% CI 0.34-0.86; P=0.009), with an overall inhibitor usage rate of 4.1%. n the group with rare cancer (n=2,156; 38% altered; e.g., appendiceal, sinonasal, biliary), less than 3% of patients used inhibitors (n=22), and non-White patients had an aOR of 0.31 (95%CI 0.15-0.65; P=0.002). The disparity in CGP-to- therapy utilization was significant across community practices (12% inhibitor use versus 28% academic; P < 0.001), safety-net hospitals (OR 0.41; 95% CI0.32-0.53), and among Medicaid-insured patients (OR 0.38; 95% CI 0.28-0.51). Sensitivity analyses validated robustness: PIK3CA hotspot mutations (n=10,293) yielded comparable gaps (Black aOR 0.59), while PTEN/AKT1 mutations generated even more substantial gaps (Black aOR 0.45).Socioeconomic quintile explained 35% of the variation, while residual variances associated with practice type and region persisted. These findings underscore systemic barriers extending beyond biology, including the underutilization of CGP (Black 42% vs. White 67%; P<0.001), trial exclusion (non-White <15% in PI3K baskets), and referral biases, among numerous others. Recommendations for immediate action include making CGP a requirement in community oncology (for example, expanding CMS reimbursement), setting different accrual targets for basket trials (like NCI-MATCH and MyeloMATCH), using real-world evidence analytics to help with regulatory bridging in rare or early- onset cases, and using AI-enhanced EHR tools to keep an eye on equity. To make precision oncology fair, study showed to take action based on data to fill in these gaps so that all patients with mutation can benefit from PI3K inhibitors, no matter their race, age, or how rare they are Clinical trial registration: N/A (retrospective real-world evidence study).
