First-line systemic therapy following adjuvant immunotherapy in renal cell carcinoma (RCC): An international multi-center study.
Notice bibliographique
Résumé
4529 Background: Adjuvant pembrolizumab significantly improved overall survival (OS) and is FDA-approved for adjuvant RCC treatment. However, there is a paucity of data on sequential treatment following recurrence after pembrolizumab or other immune-oncology (IO)-based therapies (PD-1 or PD-L1 inhibitors) administered in the adjuvant setting. Methods: This study included consecutive patients (pts) from 27 international centers who received adjuvant IO-based systemic RCC therapies. Safety and efficacy of subsequent systemic therapy regimens that included vascular endothelial growth factor-targeted therapies (VEGF-TT) or alternative IO-based therapies were evaluated. Progression-free survival (PFS) and OS from the time of systemic therapy initiation following adjuvant IO were estimated using the Kaplan-Meier method. Objective response rates (ORRs) were determined per RECIST 1.1 criteria. Treatment-related adverse events (trAEs) leading to treatment discontinuation, dose reduction, or steroid use were collected. Results: Among 144 pts who received adjuvant IO, median (Q1-Q3) age was 56 (50-64) years, and 105 (73%) were males. Most pts had clear cell RCC (n=130, 90%), underwent radical nephrectomy (n=136, 94%), and had high or intermediate-high risk disease (n=129, 90%) per KEYNOTE-564 risk groups. Tumors of 15 (10%) pts had sarcomatoid features. Most pts received adjuvant pembrolizumab (n=74, 51%), atezolizumab (n=40, 28%), or nivolumab plus ipilimumab combination therapy (n=16, 11%). Most common reasons for adjuvant IO cessation were treatment completion (n=65, 45%), recurrence (n=36, 25%), or toxicity (n=34, 24%). RCC did not recur in 52 (36%) pts who remained under observation, whereas 92 (64%) had recurrent disease. Following tumor recurrence, 69/92 (75%) pts received systemic therapy; the remaining 25% underwent surgery or radiotherapy. Median follow-up from systemic therapy initiation was 16.7 months. Median PFS was 16 months (95% CI = 10.4 – 41.7), and 18-month OS was 86% (95%CI: 76.4 – 97.3%). ORR was 36% (n = 25/69). Most pts received VEGF-TT (n=32, 46%), IO/VEGF-TT combinations (n=21, 30%), or single/combination IO (n=12, 17%). ORRs were comparable (35% in VEGF-TT monotherapy, 45% in IO/VEGF-TT combination, 42% in single/combination IO cohort). In 23 pts who received adjuvant pembrolizumab monotherapy and subsequent systemic therapy, ORR was 44% (4/9) vs. 29% (4/14) for those recurring after vs. prior to discontinuation of pembrolizumab, respectively. Two out of 8 pts who discontinued adjuvant IO due to toxicity were rechallenged with subsequent IO and had stable disease, and one of them developed an immune-related AE. TrAEs occurred in 28/69 (41%) pts treated with subsequent systemic therapy. Conclusions: Patients with RCC who recur on or after adjuvant IO treatment benefit from subsequent systemic therapies across different regimens.
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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| 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 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 ».