Plasma-based tumor mutational burden (bTMB) as predictor for survival in phase III EAGLE study: Durvalumab (D) 6 tremelimumab (T) versus chemotherapy (CT) in recurrent/ metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum failure
Abstract No : 6511
Abstract Type : Clinical Science Symposium
Indication : HNSCC
Intervention : Durvalumab + Tremelimumab
Company : AstraZeneca
Technology : TMB
736 intent-to-treat pts were randomized; 247 were evaluable for bTMB (BEP). bTMB expression was not linked to HPV status, PD-L1 status, age, gender, tumor location, or ECOG PS. Smoking and progression within 6 months on multi-modality CT in localized disease trended with higher bTMB. OS and PFS HRs were significantly improved for D or D+T vs CT in pts with high bTMB ($16 mut/Mb) vs low (,16 mut/ Mb; Table). The benefit of D or D+T vs CT in pts with high bTMB generally improved with increasing cutoff. 74 pts (27 D, 20 D+T, 27 CT pts) were bTMB high. 18-month OS rates were higher for D+T (22%; 95% CI 7%–42%) and D (33%; 95% CI 17%–51%) vs CT (0%; 95% CI 0%–0%) in pts with high bTMB. Pts with mutations in KMT2D, a HNSCC tumor suppressor gene, showed improved OS for D+T vs CT (HR 0.39; 95% CI 0.18–0.85). A trend of improved OS for D+T vs CT (HR 0.19; 95% CI 0.03–1.03) was also seen in pts with ATM mutations
This is the first retrospective analysis of a phase 3 trial to show bTMB may be predictive of outcomes for checkpoint inhibitors in R/M HNSCC. In pts with high bTMB, D or D+T improved OS hazards by at least 60%, vs CT at cutoffs $16 mut/Mb. Validation of bTMB as a predictive biomarker is ongoing.
Future directions based on TMB studies: Is there will be different implications for anti PD-1/PDL-1 vs anti-CTLA4? Is it better for first line or second line? Is it more suitable for combination of Immunecheckpoint inhibitors? Does PDL-1/CPS complement bTMB as predictive biomarker?