1516P Health-related Quality of Life (hrqol) Analysis from KEYNOTE-859: First-line (1L) Pembrolizumab (pembro) + Chemotherapy (chemo) for Advanced HER2-negative Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma

In the phase III KEYNOTE-859 study (NCT03675737), 1L pembro + chemo significantly improved OS, PFS, and ORR vs placebo (pbo) + chemo regardless of PD-L1 expression and had a manageable AE profile in patients (pts) with locally advanced/metastatic HER2-negative G/GEJ adenocarcinoma. Prespecified exploratory HRQoL outcomes are reported. HRQoL was assessed in treated pts who completed ≥1 HRQoL assessment using the EORTC QLQ-C30, EORTC QLQ-STO22, and EQ-5D-5L questionnaires. Least squares mean (LSM) changes from baseline (BL) to wk 18 in QLQ-C30 GHS/QoL; physical functioning (PF) and role functioning (RF) subscales; nausea/vomiting and appetite loss symptoms scales; QLQ-STO22 pain symptom scale; and EQ-5D-5L VAS were compared using a constrained longitudinal data analysis model (covariates: Tx by study visit interaction and stratification factors). Time to deterioration (TTD; ≥10-point decline from BL in a given scale/subscale) was estimated using the Kaplan-Meier method; between-arm difference (HR) was determined using a stratified Cox proportional hazards model. The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was wk 18. From BL to wk 18, LSM changes in QLQ-C30 GHS/QoL, PF, RF, nausea/vomiting, and appetite loss and EQ-5D-5L VAS were similar between arms; the QLQ-STO22 pain scale favored pembro + chemo (Table). TTD (HR; 95% CI) in QLQ-C30 GHS/QoL (0.87; 0.72-1.04), PF (0.91; 0.76-1.08), RF (0.90; 0.76-1.06), appetite loss (1.00; 0.82-1.22), and nausea/vomiting (0.95; 0.79-1.14) were similar between arms; the QLQ-STO22 pain scale favored pembro + chemo (0.76; 0.58-0.98). Table: 1516PChange from BL to wk 18, LSM (95% CI)Difference in LSM change from BL to wk 18 (95% CI)Pembro + chemoPbo + chemoEORTC QLQ-C30n = 771n = 771N/AGHS/QoL0.40 (-1.37 to 2.18)-0.85 (-2.62 to 0.93)1.25 (-1.07 to 3.58)PF-5.87 (-7.53 to -4.22)-7.53 (-9.18 to -5.88)1.65 (-0.64 to 3.94)RF-5.41 (-7.59 to -3.22)-7.97 (-10.15 to -5.79)2.57 (-0.38 to 5.52)Nausea/vomiting1.06 (-0.75 to 2.87)1.36 (-0.45 to 3.16)-0.30 (-2.67 to 2.07)Appetite loss-3.43 (-6.10 to -0.76)-4.85 (-7.51 to -2.19)1.42 (-1.93 to 4.77)EORTC QLQ-STO22 painn = 754 -8.21 (-9.91 to -6.51)n = 752 -5.64 (-7.34 to -3.94)-2.57 (-4.72 to -0.41)EQ-5D-5L VASn = 771 -0.69 (-2.12 to 0.73)n = 771 -1.91 (-3.33 to -0.49)1.22 (-0.65 to 3.08) Open table in a new tab HRQoL data from KEYNOTE-859, combined with efficacy and safety results, support a favorable benefit-to-risk profile for pembro + chemo as a new 1L Tx option for advanced HER2-negative G/GEJ adenocarcinoma.