Abstract CT073: Pembrolizumab after two or more lines of prior therapy in patients with advanced small-cell lung cancer (SCLC): Results from the KEYNOTE-028 and KEYNOTE-158 studies
Notice bibliographique
Résumé
Abstract Background: The antitumor activity of the anti-PD-1 monoclonal antibody pembrolizumab in patients with advanced SCLC has been evaluated in the Phase Ib basket study KEYNOTE-028 (KN028; NCT02054806) and in the Phase II basket study KEYNOTE-158 (KN158; NCT02628067). We present outcomes for patients enrolled in KN028 and KN158 who were receiving pembrolizumab after ≥2 lines of prior therapy. Methods: Eligible patients had histologically/cytologically confirmed incurable advanced SCLC, measurable disease per RECIST 1.1, ECOG PS of 0/1, had experienced progression/failure on standard therapy, and were immunotherapy-naive; patients included in this analysis had received ≥2 lines of systemic therapy. Patients in KN028 were required to have PD-L1-positive tumors (membranous PD-L1 expression in ≥1% of tumor and associated inflammatory cells or positive staining in stroma); tumor PD-L1 expression was not required in KN158. Radiographic imaging was performed Q8W for 6 mo (KN028) or Q9W for 1 y (KN158), and Q12W thereafter. Pembrolizumab (10 mg/kg Q2W [KN028] or 200 mg Q3W [KN158]) was administered for 2 y or until disease progression or intolerable toxicity. The primary endpoint in both studies was objective response rate (ORR) assessed per RECIST 1.1. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were secondary endpoints and estimated using the Kaplan-Meier method. For this analysis, assessment of response was by independent central review. Results: Of 131 SCLC pts included in both trials, 83 were eligible for efficacy analyses (KN158, n=64; KN028, n=19). Median age was 62 (range, 24–84) y, 64% were men, and 36% had received ≥3 lines of systemic therapy. As of the data cutoff date, median follow-up was 7.7 (range, 0.5–48.7) mo. The ORR was 19.3% (95% CI, 11.4-29.4). Two patients had a complete response and 14 had a partial response per independent central review; 14 of 16 responders were PD-L1-positive. Median DOR was not reached (range, 4.1-35.8 [ongoing] mo). 9 of 16 responders (61% per Kaplan-Meier estimate) had response lasting ≥18 mo. Median PFS was 2.0 (95% CI, 1.9-3.4) mo and median OS was 7.7 (95% CI, 5.2-10.1) mo. 12- and 24-month rates were 16.9% and 13.1% for PFS, and 34% and 21% for OS. Among all SCLC patients in KN028 and KN158 irrespective of prior therapies (N=131), 8% had a grade 3 treatment-related AE (no grade 4 treatment-related AEs). 3 patients had grade 5 treatment-related AEs (intestinal ischemia, pneumonia, encephalopathy). 21% experienced an immune-mediated AE or infusion reaction. Conclusions: Pembrolizumab demonstrated promising antitumor activity in patients with advanced SCLC who had received ≥2 lines of prior therapy. Responses were durable, with the majority of patients estimated to have a response duration of at least 18 mo. No unexpected toxicities from pembrolizumab were observed. Citation Format: Hyun Cheol Chung, Sarina A. Piha-Paul, Jose Lopez-Martin, Jan H.M. Schellens, Steven Kao, Wilson H. Miller Jr., Jean-Pierre Delord, Bo Gao, David Planchard, Maya Gottfried, Alona Zer, Shadia I. Jalal, Nicolas Penel, Janice M. Mehnert, Ignacio Matos, Jaafar Bennouna, Dong-Wan Kim, Lei Xu, Suba Krishnan, Kevin Norwood, Patrick A. Ott. Pembrolizumab after two or more lines of prior therapy in patients with advanced small-cell lung cancer (SCLC): Results from the KEYNOTE-028 and KEYNOTE-158 studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT073.
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 | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».