Phase I/Ib study of inavolisib (INAVO) alone and in combination with endocrine therapy ± palbociclib (PALBO) in patients (pts) with <i>PIK3CA</i> -mutated, hormone receptor–positive, HER2-negative locally advanced/metastatic breast cancer (HR+, HER2– LA/mBC): Analysis of hyperglycemia (HG) in prediabetic/obese pts.
Bibliographic record
Abstract
1004 Background: INAVO, a highly potent and selective PI3Kα inhibitor that also promotes degradation of mutated p110α, is approved by the FDA in combination with PALBO + fulvestrant (FULV) for PIK3CA -mutated, HR+, HER2–, endocrine-resistant advanced BC. HG is a common on-target side effect of PI3K inhibitors. There are limited data for PI3K inhibitors in prediabetic/obese pts. Data from prediabetic/obese pts with HR+, HER2– LA/mBC treated with INAVO from a Phase I/Ib study (GO39374; NCT03006172) are reported here. Methods: Adults ≥ 18 years of age received INAVO alone (Arm A), + letrozole (LET) + PALBO (Arm B), + LET (Arm C), + FULV (Arm D), + FULV + PALBO (Arm E), or + FULV + PALBO + primary prophylactic metformin (Arm F). Data are reported across all arms unless indicated. Pts with baseline risk factors for HG were defined by HbA 1c ≥5.7%, fasting blood glucose ≥ 100 mg/dL, or body mass index ≥ 30 kg/m 2 . Adverse events (AEs) were reported using NCI-CTCAE v4, which utilizes fasting laboratory glucose values for HG severity grading, rather than clinical interventions used in v5. Results: Clinical cut-off was Jan 1, 2024. From190 pts treated, 110 (57.9%) were prediabetic/obese; their median time on INAVO was 222 days (range, 7 to 2,152) and mean cumulative dose intensity was 91.8%. Most prediabetic/obese pts discontinued INAVO due to progressive disease (82 [74.5%]); six (5.5%) discontinued INAVO due to an AE (one due to HG). HG was reported in 80.9% of prediabetic/obese pts (grade 3–4: 34.5%). In pts with two risk factors, 87.9% reported HG (grade 3–4: 39.4%). Among pts with HG, median time to onset was 14 days (range, 1 to 1,674) and 86.0% of events resolved by clinical cut-off. Median time to improvement or resolution of first worst grade ≥ 2 event was 8 days (range, 1 to 64). INAVO dose interruptions, reductions, and discontinuations due to HG were reported in 41.8%, 13.6%, and 0.9% of pts, respectively. The most common anti-HG medications were metformin (52.7%; biguanide; concomitant use in Arm F excluded), empagliflozin (25.5%; SGLT-2 inhibitor), sitagliptin (22.7%; DPP-4 inhibitor), and pioglitazone (13.6%; thiazolidinedione); insulin was used in 8.2% of pts. Median time to metformin start (excluding Arm F) was 14 days (range, 1 to 1,710); the median start dose was 1,000 mg total daily; and the highest daily start dose was 2,000 mg. More than one anti-HG medication was often needed. Conclusions: A high proportion of prediabetic/obese pts were included in GO39374. In most of these pts, HG was manageable with dose interruptions and oral anti-HG medications, most commonly metformin. Data support the use of INAVO in prediabetic/obese pts; further investigation of INAVO in pts with diabetes is warranted. Clinical trial information: NCT03006172 .
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".