Safety and antitumor activity of pembrolizumab in patients with advanced microsatellite instability–high (MSI-H) colorectal cancer: KEYNOTE-164
Notice bibliographique
Résumé
Introduction: Approval of pembrolizumab as treatment for adult and pediatric patients with unresectable or metastatic previously treated MSI-H or mismatch repair–deficient cancer, regardless of tumor type or site, was partly based on data from cohort A of the phase 2 KEYNOTE-164 (NCT02460198) study of patients with MSI-H colorectal cancer (CRC) after ≥2 prior lines of standard therapy. Data are presented herein from cohort B of KEYNOTE-164, which was conducted to evaluate pembrolizumab in patients with metastatic MSI-H CRC previously treated with ≥1 line of therapy. Methods: Cohort B of the KEYNOTE-164 study enrolled patients with metastatic CRC who had locally confirmed MSI-H status per immunohistochemistry or polymerase chain reaction and had received ≥1 prior line of therapy (irinotecan, oxaliplatin, fluoropyrimidine, or anti-vascular endothelial growth factor/endothelial growth factor receptor). Patients received pembrolizumab 200 mg every 3 weeks (Q3W) for 2 years or until progression, unacceptable toxicity, or withdrawal of consent. Tumor response was assessed per RECIST v1.1 by independent review Q9W. End points included objective response rate (ORR) (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary). Results: Sixty-three patients were enrolled; median age was 59 years (range: 23-83); 52% were male. Most patients (94%) had ≥1 prior therapy for advanced disease; median number of prior therapies was 2. As of September 12, 2017, median follow-up was 12.6 months (range: 0.1-15.4). ORR was 32% (95% CI, 21-45), with 2 complete responses and 18 partial responses. Median DOR was not reached (NR); 95% of responses were ongoing; and DOR for 75% of responders was ≥6 months. Median PFS was 4.1 months (95% CI, 2.1-NR) and median OS was NR. The 12-month PFS rate was 41% and the 12-month OS rate was 76%. Forty (64%) patients experienced treatment-related adverse events (AEs) of any grade, most commonly (≥10%) fatigue (18%), hypothyroidism (16%), and hyperthyroidism (11%). Seven (11%) patients had grade ≥3 treatment-related AEs of anemia, thrombocytopenia, diarrhea, pneumatosis intestinalis, pneumonitis, syncope, arthritis, and vasculitis (n = 1 each). There were no treatment-related deaths. Twenty (32%) patients had immune-mediated AEs of any grade. Two (3%) patients had grade ≥3 immune-mediated AEs of pneumonitis and colitis (n = 1 each). Conclusion: Pembrolizumab demonstrated durable antitumor activity with a safety profile that was manageable in cohort B of KEYNOTE-164, which was conducted to evaluate patients with MSI-H CRC whose disease progressed after ≥1 line of prior therapy.
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) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».