Real-world effectiveness of pembrolizumab among patients with TMB-H advanced solid tumors.

Abstract

e23360 Background: Pembrolizumab has been conditionally approved for previously treated solid tumor patients with high tumor mutational burden (TMB-H ≥10 mut/Mb, as determined by an FDA-approved test) who lack satisfactory alternative treatment options. Real-world evidence of pembrolizumab effectiveness in the TMB-H population is limited. Methods: We conducted a retrospective study to evaluate the effectiveness of pembrolizumab in TMB-H patients using the US-based deidentified Flatiron Health-Foundation Medicine Pan-Tumor Clinico-Genomic Database. All adult patients with advanced/metastatic solid tumors (excluding melanoma and NSCLC), who were TMB-H (based on FoundationOne CDx), non-microsatellite instability high and received pembrolizumab monotherapy in 2L/2L+ were included. Real-world response (rwR) assessment was abstracted through manual medical chart review, based on clinician documentation following radiographic imaging. The prespecified primary analysis included patients with ≥1 rwR assessment. Real-world response rate (rwRR) was the proportion of patients with a complete response (rwCR) or partial response (rwPR). Results: The primary population included 306 patients across 25 tumor types, most commonly bladder, breast, and gastric. Median age was 68 years; 51.8% female; 80.3% non- Hispanic/Latino; 105 patients had a response, yielding a rwRR 34.3%. The rwRR was 25.2% (95% CI:17.6–34.2) for TMB 10-13 mut/Mb (n=29) and 39.8% (95% CI: 32.8–47.1) for TMB ≥13 mut/Mb (n=76). Median duration of response was 14.5 months; median time to response was 2.8 months. Sensitivity analysis with all patients (counting those without rwR assessment as non-responders) is shown in the table. Conclusions: This observational study reflects real-world practice, including non-standardized visit schedules and chart-abstracted responses without imaging re-read, which may limit comparability of rwRR to the ORR by RECIST in clinical trials. Nevertheless, these findings were consistent with the trial that supported the approval and provided complementary evidence on pembrolizumab effectiveness in TMB-H cancers treated in routine care. Real-world responses among the study populations. Primary population (n=306) All population (n=407) n (%) 95% CI n (%) 95% CI Response (CR or PR) 105 (34.3) (29.0, 39.9) 105 (25.8) (21.6, 30.3) Complete Response (CR) 30 (9.8) (6.7, 13.7) 30 (7.4) (5.0, 10.4) Partial Response (PR) 75 (24.5) (19.8, 29.7) 75 (18.4) (14.8, 22.5) Non-Response 201 (65.7) (60.1, 71.0) 302 (74.2) (69.7, 78.4) Stable Disease (SD) 65 (21.2) (16.8, 26.3) 65 (16.0) (12.5, 19.9) Progressive Disease (PD) 126 (41.2) (35.6, 46.9) 126 (31.0) (26.5, 35.7) Pseudo-Progression 7 (2.3) (0.9, 4.7) 7 (1.7) (0.7, 3.5) Indeterminate response 1 (0.3) (0.0, 1.8) 1 (0.2) (0.0, 1.4) Not documented 2 (0.7) (0.1, 2.3) 2 (0.5) (0.1, 1.8) No response assessment - - 101 (24.8) (20.7, 29.3)