التفاصيل البيبلوغرافية
| العنوان: |
Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma |
| المؤلفون: |
Robert, Caroline, Hwu, Wen-Jen, Hamid, Omid, Ribas, Antoni, Weber, Jeffrey S, Daud, Adil I, Hodi, F Stephen, Wolchok, Jedd D, Mitchell, Tara C, Hersey, Peter, Dronca, Roxana, Joseph, Richard W, Boutros, Celine, Min, Le, Long, Georgina V, Schachter, Jacob, Puzanov, Igor, Dummer, Reinhard, Lin, Jianxin, Ibrahim, Nageatte, Diede, Scott J, Carlino, Matteo S, Joshua, Anthony M |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2021 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Cancer, Vaccine Related, Immunization, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, Clinical Trials as Topic, Drug-Related Side Effects and Adverse Reactions, Female, Follow-Up Studies, Humans, Male, Melanoma, Meta-Analysis as Topic, Middle Aged, Prognosis, Young Adult, Pembrolizumab, Advanced melanoma, Immune-related adverse events, Immune-checkpoint inhibitors, PD-1 inhibitors, Immunomodulating drugs |
| الوصف: |
ObjectiveLong-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006.Patients and methodsAnalysis involved patients who received ≥1 pembrolizumab dose. Lead-time bias was addressed via landmark analyses in patients who were progression-free before day 147.ResultsAdverse events (AEs) were analyzed for 1567 patients (median follow-up, 42.4 months). Most AEs were mild/moderate; grade 3/4 treatment-related AEs occurred in 17.7% of patients. Two pembrolizumab-related deaths occurred. Any-grade immune-mediated AEs (imAEs) occurred in 23.0%, most commonly hypothyroidism (9.1%), pneumonitis (3.3%), and hyperthyroidism (3.0%); grade 3/4 imAEs occurred in 6.9% of patients. Most imAEs occurred within 16 weeks of treatment. In landmark analysis, patients who did (n=79) versus did not (n=384) develop imAEs had similar objective response rates (ORRs) (64.6% versus 63.0%); median time to response (TTR), 5.6 months for both; median duration of response (DOR), 20.0 versus 25.3 months; median progression-free survival (PFS), 17.0 versus 17.7 months; median overall survival (OS), not reached (NR) versus 43 months (p=0.1104). Patients who did (n=17) versus did not (n=62) receive systemic corticosteroids had similar ORRs (70.6% vs. 62.9%) and median TTR (6.4 vs. 5.6 months) but numerically shorter median PFS (9.9 vs. 17.0 months); median DOR, 14.2 months versus NR; median OS, NR for both.ConclusionsThese results enhance the knowledge base for pembrolizumab in advanced melanoma, with no new toxicity signals after lengthy follow-up of a large population. In landmark analyses, pembrolizumab efficacy was similar regardless of imAEs or systemic corticosteroid use.Clinical trial registryNCT01295827, NCT01704287, NCT01866319. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt275859cs; https://escholarship.org/uc/item/275859csTest |
| الإتاحة: |
https://escholarship.org/uc/item/275859csTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.26AF0208 |
| قاعدة البيانات: |
BASE |
