In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 4512-4512
Abstract:
4512 Background: KEYNOTE-061 (NCT02370498) was a randomized, open-label, phase 3 study of pembrolizumab vs paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma with tumor progression after first-line therapy (N =592). We explored the association of tissue tumor mutational burden (tTMB) status and clinical outcomes in patients with GC enrolled in KEYNOTE-061, including the relationship with PD-L1 combined positive score (CPS) and microsatellite instability-high (MSI-H) status. Methods: In patients from KEYNOTE-061 with evaluable tumor and matched normal whole exome sequencing (WES) data (N = 420; pembrolizumab, 218; paclitaxel, 202), the association of tTMB (continuous log 10 scale) with confirmed ORR and PFS by blinded central radiology review per RECIST v1.1, and OS was evaluated within each treatment arm using logistic regression (ORR) and Cox proportional hazards regression (PFS; OS). The clinical utility of tTMB was assessed using the prespecified cutoff of 175 mut/exome. Clinical data cutoff: October 26, 2017. Results: tTMB was significantly associated (α=0.05) with ORR, PFS, and OS in patients treated with pembrolizumab (one-sided P 〈 0.001) but not paclitaxel (two-sided P 〉 0.600). The area under the receiver operating characteristics curve for tTMB and response (pembrolizumab vs paclitaxel) was 0.68 (95% CI, 0.56-0.81) vs 0.51 (95% CI, 0.39-0.63). Patient outcomes by tTMB cutoff are reported in Table. There was low correlation between tTMB and PD-L1 CPS in both treatment arms (r 〈 0.18). tTMB remained significantly associated with all clinical end points with pembrolizumab after adjusting for PD-L1 CPS and with PFS and OS after excluding MSI-H patients. Conclusions: This exploratory analysis from KEYNOTE-061 is the first to demonstrate a strong association between tTMB and response to pembrolizumab in patients with GC. Data further suggest tTMB is a significant and independent predictor beyond PD-L1 status. Clinical trial information: NCT02370498 . [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.4512
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
