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.
Notice bibliographique
Résumé
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 .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».