P3-16-01: Safety Profile and Clinical Activity of Single-Agent BKM120, a Pan-Class I PI3K Inhibitor, for the Treatment of Patients with Metastatic Breast Carcinoma.
Bibliographic record
Abstract
Abstract Background Phosphatidylinositol 3-kinase (PI3K) is critical to cancer cell growth, survival, and metabolism. BKM120 is an oral pan-class I (α, β, γ, δ) PI3K inhibitor that has demonstrated in vitro and in vivo tumor cell growth inhibition in a range of cancer types including breast cancer. Materials and methods: The Phase I study CBKM120X2101 investigating single-agent daily BKM120 in patients (pts) with advanced solid tumors has been recently completed with the maximum tolerated dose established at 100 mg/day. Here, we report the analysis of metastatic breast carcinoma (MBC) pts enrolled in this study. Results: Overall, 83 pts have enrolled, 21 of whom have MBC. At the cut-off date of 25th February 2011, 20 MBC pts were evaluable: 1 pt at 80 mg, 1 pt at 150 mg and 18 pts at 100 mg. Patient characteristics were as follows: median age 55 years (range 37–71); performance status ECOG 0/1/2 for 7/12/1 pts, respectively; visceral disease was reported in 16 pts, including liver, 10 pts (50%); lung, 9 pts (45%); and pleura, 5 pts (25%); all pts had >3 lines of systemic therapy (3-12). The median time from last treatment and study entry was 46 days (29-235). The median duration of BKM120 treatment administered was 7.5 weeks (1.0−96.4). The most frequent grade 3 drug-related adverse events (AEs) were: transaminases increase, 4 pts; psychiatric disorders, 3 pts, consisting of anxiety, affective disorder, and mood alteration (1 pt each); diarrhea, 2 pts; fatigue, 2 pts; and hyperglycemia, 1 pt. The only grade 4 drug-related AE was hyperglycemia, reported in 1 pt at 150 mg. Most AEs were manageable with treatment interruption and dose reductions. Eighteen pts were evaluable for objective tumor response by RECIST. Two pts (11%) exhibited partial responses, which were confirmed in a triple-negative MBC pt, and unconfirmed in an ER+ HER2− MBC pt. For these 2 pts, the treatment duration was 29+ (ongoing) and 6 months, respectively. An additional 9 pts (50%) had stable disease, lasting >4 months in 7 pts (35%). Conclusions: This preliminary analysis showed that BKM120 has single-agent activity in heavily pretreated pts with MBC, and an acceptable safety profile. Molecular profiling and updated pharmacokinetic results will be presented at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-01.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".