P2, N=30, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting

P3, N=315, Active, not recruiting, AstraZeneca | Trial completion date: Nov 2027 --> Sep 2028

P3, N=300, Not yet recruiting, Genentech, Inc.

P3, N=1520, Not yet recruiting, West German Study Group | N=1050 --> 1520

P3, N=1000, Recruiting, Olema Pharmaceuticals, Inc.

To achieve cost-effectiveness at WTP thresholds of $100,000, $150,000, and $200,000 per QALY, the per-cycle price of inavolisib would need to be reduced to 59.5%, 72.0%, and 86.5% of its current price, respectively.ConclusionFor patients with PIK3CA-mutated HR+/HER2- ABC, the inavolisib regimen is not cost-effective in the U.S. healthcare setting. Negotiating price reductions and adjusting decision thresholds based on patient characteristics may be viable strategies to meet the extensive treatment demand in the U.S.

This trial adopted a Simon two-stage design: eligible patients received tucidinostat plus metronomic capecitabine together with either an aromatase inhibitor (Cohort 1) or fulvestrant (Cohort 2), selected according to prior ET. In addition, exploratory analyses of biomarkers indicated that the baseline TP53 mutation status (Wild type vs. mutated, 7.64 months vs. 3.55 months) and circulating tumor cell (CTC) status (CTC-negative vs. CTC-positive, 7.59 months vs. 3.78 months) were associated with the median PFS. Our study demonstrated that tucidinostat combined with mCAP and ET is efficacious and well-tolerated in patients with HR-positive HER2-negative ABC previously treated with CDK4/6i.

The AKT inhibitor capivasertib has demonstrated clinical benefit in combination with the selective ER degrader fulvestrant in PIK3CA, PTEN and AKT-1 altered estrogen receptor positive breast cancer (ER+ BC). Rather than influencing gene expression, loss of KDM5C combined with capivasertib increased cell stress, DNA damage, cell cycle arrest and cell death. Collectively the data suggests that chromatin regulators may have different functions following capivasertib treatment, with inhibition having potential to enhance sensitivity to capivasertib in PIK3CA, PTEN and AKT-1 altered ER+ BC cells.

Background: Alpelisib plus fulvestrant improves outcomes in PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. Evening alpelisib preceded by fasting and low-carbohydrate guidance may improve metabolic tolerability without compromising efficacy or QoL. These findings support evaluation in a larger trial incorporating prospective metabolic adherence and pharmacokinetic assessments.

Alpelisib plus fulvestrant provides clinical benefit for patients with PIK3CA-altered, HR+, HER2- ABC across a range of concomitant alterations, including those previously implicated in endocrine therapy or CDK4/6i resistance. Machine learning models identified factors including gene mutations that influenced PFS.

P1/2, N=65, Recruiting, Sarah Sammons, MD | Not yet recruiting --> Recruiting | Initiation date: Mar 2026 --> Nov 2025

Fulvestrant treatment had no significant inhibitory effect on IL-6 protein expression, whereas Stattic intervention inhibited ERα expression. The combined use of fulvestrant and Stattic significantly suppressed the proliferation and migration of TSC2-deficient cells, indicating that the IL-6/signal transducer and activator of transcription 3 (STAT3) pathway plays an important role in E2-promoted LAM progression and may serve as a potential therapeutic target for LAM.