Abstract P3-11-01: An updated systematic review and meta-analysis of the safety and efficacy of phosphoinositide 3-kinase inhibitors (PI3Ki) in advanced breast cancer
Notice bibliographique
Résumé
Abstract Background In advanced breast cancer (ABC), the addition of pan-PI3Ki to the standard of care (SOC) treatment improves tumor response rate and progression free survival (PFS). Yet, further development of these drugs has been limited by their safety profile. Instead, selective PI3Ki were assessed and the Food and Drug Administration has recently approved the use of a selective PI3Ki based on a phase 3 randomized trial. Therefore, we updated our systematic review and meta-analysis to evaluate whether there is a difference in the efficacy and/or safety of pan versus selective PI3Ki in ABC. Methods The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials and Embase, were searched for relevant publications reporting randomized controlled trials between January 2000 and June 2019. Pooled hazard ratios (HR) for progression-free survival (PFS), and pooled odds ratios (OR) for objective response rate (ORR), disease control rate (DCR) and toxicity were computed and weighted using Mantel-Haenszel method and generic inverse variance. Subgroup analyses compared patients with and without PI3K pathway activation. Results Seven studies comprising 3,597 patients were included (5 studies with pan-PI3Ki and 2 studies with selective PI3Ki). Pan and selective PI3Ki decreased the risk of progression by 21% and 32% compared to SOC: HR: 0.79, 95%CI 0.0.71-0.88 and 0.68, 95%CI 0.57-0.81 respectively, p for test for subgroup differences: 0.16. An improvement in ORR was more pronounced with the use of selective versus pan PI3Ki: OR 2.67, 95%CI 1.78-4.00 and OR 1.31, 95%CI 1.01-1.71 respectively, p for test for subgroup differences: 0.004 and DCR was only improved with selective PI3Ki: OR 1.85 95%CI 1.37-2.51. A statistically significant increase in the toxicity of any grade and of grade 3 and higher was observed with pan and selective PI3Ki: 1) for any grade toxicity: OR 5.51, 95%CI 3.05-9.96, and OR 3.77, 95%CI 2.16-6.58 respectively, p for test for subgroup differences 0.16; 2) for grade 3 or higher toxicity: OR 1.91, 95%CI 1.76-2.08 and OR 2.41, 95%CI 2.07-2.82 respectively; p for test for subgroup difference 0.01. In subgroup analyses, the PFS improvement was more pronounced in the PI3K mutant subgroup: HR 0.72, 95%CI 0.63-81 for the PI3K mutant subgroup and HR 0.83, 95%CI 0.73-0.96 for the PI3K wild-type subgroup, p for test for subgroup differences 0.11. Conclusion While selective PI3Ki have a better effect on ORR, DCR and PFS in patients with ABC compared to pan PI3Ki; their toxicity profile is still clinically substantial. Rigorous safety monitoring and early medical intervention are needed to reduce treatment discontinuation, optimize efficacy and render these drugs more clinically usable. Citation Format: Jacques Raphael, Syed Hussaini, Kathleen I Pritchard, Prakesh Shah, Phillip Blanchette, Ricardo Fernandes, Danielle Desautels. An updated systematic review and meta-analysis of the safety and efficacy of phosphoinositide 3-kinase inhibitors (PI3Ki) in advanced breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-01.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,000 | 0,003 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
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 tête enseignante, 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 ».