Abstract PD13-09: Impact of neratinib on outcomes in HER2-positive metastatic breast cancer patients with central nervous system disease at baseline: Findings from the phase 3 NALA trial
Notice bibliographique
Résumé
Abstract Background: The development of central nervous system (CNS) metastases presents a considerable challenge in metastatic breast cancer (MBC) due to the limited availability of evidence-based treatments. Up to 50% of patients with HER2-positive (HER2+) MBC develop CNS metastases during the course of their disease. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated activity against CNS metastases in HER2+ MBC in two phase 2 studies (NEfERT-T, TBCRC 022) and one phase 3 study (NALA); significant benefits for predefined CNS endpoints were reported in NEfERT-T and confirmed in NALA. Here we present an exploratory analysis of patients from NALA with CNS involvement at enrollment. Methods: NALA was an international, randomized, open-label, active-controlled, phase 3 study in patients with HER2+ MBC who had received ≥2 lines of HER2-directed therapy in the metastatic setting (ClinicalTrials.gov: NCT01808573). Patients with asymptomatic metastatic brain disease managed with stable doses of corticosteroids for ≥14 days prior to randomization were eligible, whereas patients with symptomatic or unstable brain metastases were excluded. Patients were randomized (1:1 ratio) to neratinib (N; 240 mg qd po) + capecitabine (C; 750 mg/m2 bid po) or lapatinib (L; 1250 mg qd po) + C (1000 mg/m2 bid po). Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Intervention for symptomatic metastatic CNS disease was a secondary endpoint. CNS disease at baseline was defined as patients with treated or untreated disease in the ‘brain’ assessed by investigator at enrollment. CNS imaging was not mandatory at screening. Results: Of the 621 patients enrolled in NALA, 101 (16%) had documented baseline CNS disease and 520 (74%) had no CNS disease at baseline. Patients with CNS disease had a lower performance status and were more likely to have hormone receptor-negative disease than those with no CNS disease; no major imbalances of baseline characteristics were noted between treatment arms. Overall, 78 (77%) patients had previously received CNS radiation [whole brain, n=59 (58%); stereotactic, n=17 (17%); unknown, n=2 (2%)], and 5 (5%) patients had undergone CNS surgery. Median treatment duration was 5.7 (IQR 2.8-8.5) months for N, and 3.5 (IQR 2.1-6.9) months for L. PFS, OS, and cumulative incidence of interventions for symptomatic CNS disease are summarized in the table. No new safety signals were detected. Conclusions: Regardless of the status of CNS metastases at baseline, patients appeared to have better outcomes in the N+C arm compared with the L+C arm. Table. Efficacy outcomes in patients with and without CNS disease at baselineIntention-to-treat (n=621)CNS metastases at baseline – Yes (n=101)CNS metastases at baseline – No (n=520)N+C (n=307)L+C (n=314)N+C (n=51)L+C (n=50)N+C (n=256)L+C (n=264)PFSaHazard ratio (95% CI)0.76 (0.63–0.93)0.66 (0.41–1.05)0.76 (0.62–0.94)P-value0.00590.07410.0099Restricted mean PFSb, months8.86.67.85.59.06.9Difference, months2.22.32.1OSHazard ratio (95% CI)0.88 (0.72–1.07)0.90 (0.59–1.38)0.85 (0.68–1.06)P-value0.20860.63520.1517Restricted mean OSb, months24.022.216.415.425.623.6Difference, months1.71.02.0Incidence of CNS interventionOverall cumulative incidencec, %22.7629.1940.1347.7919.1624.65P-value0.0430.4300.067aCentrally confirmed; bRestriction prespecified as 24 months for PFS, and 48 months for OS; c % requiring intervention for CNS disease (competing risk model) Citation Format: Cristina Saura, Larisa Ryvo, Sara Hurvitz, William Gradishar, Beverly Moy, Suzette Delaloge, Sung-Bae Kim, Mafalda Oliveira, Maureen Trudeau, Ming-Shen Dai, Barbara Haley, Ron Bose, Luciana Landeiro, Judith Bebchuk, Aimee Frazier, Kiana Keyvanjah, Richard Bryce, Adam Brufsky. Impact of neratinib on outcomes in HER2-positive metastatic breast cancer patients with central nervous system disease at baseline: Findings from the phase 3 NALA trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD13-09.
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 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) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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 ».