Abstract PS14-08: Safety evaluation from the KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer
Notice bibliographique
Résumé
Abstract Background: In KEYNOTE-355 (NCT02819518), pembrolizumab (pembro) + chemotherapy (chemo) led to statistically significant and clinically meaningful improvements in PFS and OS (primary endpoints) vs placebo (pbo) + chemo in patients (pts) with previously untreated PD-L1 positive advanced TNBC (combined positive score ≥10). In the overall safety population at final analysis, treatment-related AEs occurred in 96.3% of pts in the pembro + chemo arm and 95.0% of pts in the pbo + chemo arm; immune-mediated AEs occurred in 26.5% and 6.4% of pts, respectively. We report additional safety information, beyond the already reported safety results, on immune-mediated AEs and management from the final analysis of KEYNOTE-355. Methods: Eligible pts were randomized 2:1 to receive pembro 200 mg or pbo Q3W for up to 35 cycles + investigator’s choice of nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin. Safety was assessed in all randomized pts who received ≥1 dose of study treatment. AEs were monitored throughout the study and for 30 d post-treatment (90 d for serious AEs). Results: At final analysis (data cut-off: June 15, 2021), median treatment duration was 6.1 (range, 0.0–48.8) mo in the pembro + chemo arm (n = 562) and 5.3 (range, 0.0–51.5) mo in the pbo + chemo arm (n = 281). Of 157 pts with immune-mediated AEs and infusion reactions in the pembro + chemo arm, 125 had grade 1-2 events and 32 had grade 3-4 events; none were grade 5. The most common immune-mediated AEs with pembro + chemo were hypothyroidism (15.8%) and hyperthyroidism (4.3%); infusion reactions occurred in 3.7% of pts (table). Of 89 pts with hypothyroidism, median time to onset was 105 d (range, 19–707 d) and 70 were treated with thyroid replacement, suggesting an endocrine abnormality and need for continued thyroid replacement. Of 24 pts with hyperthyroidism, median time to onset was 53.5 d (range, 20–209 d) and 2 were treated with corticosteroids. Of 21 pts with infusion reactions, median time to onset was 147 d (range, 1–729 d) and 10 were treated with corticosteroids. Other immune-mediated AEs of interest in the pembro + chemo arm were pneumonitis (2.5%) and adrenal insufficiency (1.4%); most of these events were grade 2–3. Of 14 pts with pneumonitis, median time to onset was 99.5 d (range, 29–288 d) and 11 were treated with corticosteroids; median episode duration was 56 d. All 8 pts with adrenal insufficiency were treated with hormone replacement. There were no reports of hypophysitis. Conclusion: In pts with previously untreated advanced TNBC, pembro + chemo had a manageable safety profile that was generally consistent with the known safety profiles of pembro and the chemo regimens. Most immune-mediated AEs and infusion reactions were grade 1-2, manageable with treatment interruption, corticosteroids, and/or hormone replacement therapy, and did not result in discontinuation of study treatment. Together with the efficacy findings, our results support pembro + chemo as a standard of care regimen for these pts. Table. Citation Format: Hope Rugo, Peter Schmid, Zbigniew Nowecki, David Cescon, Seock-Ah Im, Mastura Yusof, Carlos Gallardo, Hiroji Iwata, Carlos Barrios, Sherene Loi, Xuan Zhou, Xiaoli Zhang, Wilbur Pan, Vassiliki Karantza, Javier Cortés. Safety evaluation from the KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS14-08.
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 | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| 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) | 0,010 | 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 ».