Abstract 1642: Alectinib in treatment-naïve anaplastic lymphoma kinase-positive (<i>ALK</i>+) metastatic non-small-cell lung cancer (mNSCLC): Systematic literature review (SLR) and network meta-analysis (NMA)
Notice bibliographique
Résumé
Abstract Background: The standard of care for treatment-naïve ALK+ mNSCLC patients (pts) is an ALK tyrosine kinase inhibitor (TKI). Pts treated with crizotinib generally experience disease progression within 1 year, often within the central nervous system (CNS). As such, there is a high unmet need for CNS-active ALK TKIs. Phase III data from 2 ALK TKIs, alectinib and ceritinib, showed improved efficacy vs crizotinib and chemotherapy, respectively; however, no studies have directly compared these TKIs. We report a NMA to compare the efficacy/safety of these therapies. Methods: A SLR was conducted to identify ALK+ mNSCLC randomized controlled trials (RCTs) in treatment-naïve pts. Efficacy/safety endpoints were extracted and the feasibility of using the data in a NMA was assessed. Data were analyzed using a fixed effect analysis in WinBUGs following NICE guidelines. Results: 1194 citations were identified, of which 4 RCTs were in treatment-naïve pts (ALEX [NCT02075840], ASCEND-4 [NCT01828099], PROFILE 1014 [NCT01154140] and PROFILE 1029 [NCT01639001]). All were open-label, phase III RCTs and pts were similar in terms of age, ECOG PS, disease stage, sex and smoking status. More pts had baseline CNS metastasis (mets) in ALEX (40%) vs the other trials (26-32%). PROFILE 1029 was conducted in East Asian pts and only included in a sensitivity analysis. Chemotherapy arms differed in that pemetrexed maintenance was included in ASCEND-4 but not in the PROFILE studies. Key efficacy/safety results are shown in the Table. Data from the sensitivity analyses were similar. Conclusion: Alectinib significantly improved progression-free survival compared with other treatments in the ITT population including in pts with baseline CNS mets. Alectinib showed significantly fewer grade 3-4 AEs than ceritinib. The difference in chemotherapy arms of the 2 trials may have impacted the NMA efficacy results. Table. NMA results in treatment-naïve ALK+ mNSCLC patientsComparisonEfficacy/Safety Endpoints PFS by IRC* HR (95% CrI)Subgroup CNS Mets at Baseline* PFS by IRC HR (95% CrI)OS* HR (95% CrI)Grade 3 or 4 AEs§OR (95% CrI)Alectinib vs chemotherapy0.23 (0.15-0.34)0.21 (0.10-0.44)0.63 (0.34-1.15)0.81 (0.44-1.52)Alectinib vs crizotinib0.50 (0.36-0.70)0.37 (0.22-0.63)0.76 (0.49-1.20)0.65 (0.41-1.04)Alectinib vs ceritinib0.41 (0.25-0.67)0.31 (0.13-0.71)0.85 (0.42-1.73)0.36 (0.17-0.79)Crizotinib vs chemotherapy0.45 (0.35-0.58)0.57 (0.35-0.93)0.82 (0.54-1.24)1.24 (0.81-1.91)Ceritinib vs chemotherapy0.55 (0.42-0.72)0.70 (0.44-1.11)0.73 (0.50-1.06)2.25 (1.42-3.61)Ceritinib vs crizotinib1.22 (0.84-1.79)1.22 (0.62-2.43)0.90 (0.52-1.57)1.82 (0.96-3.44)Statistically significant differences indicated in bold based on 95% CrI; *Hazard ratio <1 indicates lower hazard (higher likelihood of PFS or OS) compared with control; §Odds ratio <1 indicates lower odds of an event compared with control. AEs, adverse events; CNS, central nervous system; CrI, credible interval; HR, hazard ratio; IRC, independent review committee; Mets, metastases; OR, odds ratio; OS, overall survival; PFS, progression-free survival Citation Format: Anna Steenrod, Michelle Orme, Katherine S. MacGilchrist, Rachel Rosenthal, Juliane Schaefer, Vlatka Smoljanovic, Emmanuel Mitry, Parneet K. Cheema. Alectinib in treatment-naïve anaplastic lymphoma kinase-positive (ALK+) metastatic non-small-cell lung cancer (mNSCLC): Systematic literature review (SLR) and network meta-analysis (NMA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1642.
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 | 0,013 | 0,031 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,012 | 0,024 |
| Bibliométrie | 0,007 | 0,007 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
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 ».