Comparing health utility scores, treatments, and outcomes in lung cancer patients with rare EGFR mutations with those with exon 19 deletion (del) and L858R mutations.

Abstract

102 Background: Precision oncology divides patients into smaller cohorts each with unique characteristics, treatment and outcomes. Cost-effectiveness assessments that rely on quality-adjusted life years will require mutation-specific health utility scores (HUS). We assessed the impact of having exon 19 del, L858R and rare EGFR mutations on outcomes and HUS. Methods: From a retrospective database of 719 patients with EGFR mutations, specific baseline EGFR mutations, clinicodemographic and treatment characteristics, and outcomes (overall survival, OS; progression-free survival, PFS) were analyzed using Cox models (adjusted hazard ratios, HR). In a subset of 289 patients with metastatic disease, serial HUS data collected through EQ-5D-5L at clinic visits were compared by mutation using t-tests. Results: Of 380 (53%) patients with exon 19 del, 288 (40%) with L858R, and 51 (7%) with rare mutations (mostly G719A/C, Exon 18 or 20 insertion, L861Q, compound mutations): 68% were female; median age was 74 years; 51% were Asian; and 74% were never smokers. In 334 Stage I-III pts, recurrence-free survival was not associated with specific mutations. In contrast, among 365 stage IV pts on TKIs, when compared to a reference of patients with exon 19 del, outcomes were worse in patients with L858R mutations (PFS: 1.35, 95% CI 1.1-1.7; OS: HR 1.39, 95% CI 1.0-1.9) and for rare mutations (PFS: 1.16 95% CI 0.7-1.9; OS: 1.45 95% CI 0.7-2.9). From an analysis of 1064 clinic encounters, different TKIs were used in similar proportions by mutation. In stable disease, mean HUS [SEM] were 0.80 [0.008] (exon 19), 0.81 [0.009] (L858R), and 0.82 [0.02] (rare mutation). Progressive disease led to significant drops in mean HUS for exon 19 (0.76 [0.01]; p = 0.01 compared to stable disease) and L858R, mean HUS = 0.74 [0.02] p < 0.001, but less so for rare mutations, mean HUS = 0.79 [0.05] p = 0.65. Conclusions: Patients in this EGFR mutated cohort had similar exposures of different TKI therapy regardless of specific EGFR mutation. L858R and rare mutations had inferior survival outcomes but similar HUS as patients with exon 19 del mutations.