Encyclopedic tumor analysis–guided therapy in refractory advanced cancers: Clinical and health-economic outcomes.

Abstract

e23145 Background: Treatment of relapsed/refractory metastatic cancers costs $128k–$293k per patient with minimal efficacy (7–45% ORR in precision-medicine trials). Febrile neutropenia adds $12k–$15k per hospitalization, while end-of-life care costs increase up to eightfold of treatment-phase levels. RESILIENT trial evaluated Encyclopedic Tumor Analysis (ETA), integrating genomic, transcriptomic, and in-vitro chemosensitivity profiling to enable organ-agnostic, combination therapy in refractory populations. Methods: Health-economic analysis of RESILIENT trial was performed (n = 126 evaluable; ≥2 prior therapy lines). All ETA-recommended agents were FDA-approved. Endpoints included ORR, clinical benefit rate (CBR), PFS, toxicity grade distribution, PFS2/PFS1 ratios, metastatic containment, and quality-of-life (QoL) preservation. Results: ORR was 42.9% (95% CI 34.3–51.4%) and CBR 90.5%, exceeding historical precision medicine trials (MyPathway 23%, MOSCATO 11%, WINTHER 13%). Among 62 patients with prior PFS ≤90 days, 75.8% achieved PFS2/PFS1 > 1.3× and 35.5% ≥2.5×. Grade ≥3 adverse events occurred in 39.9%, with dose adjustments required in only 32.9% (vs. 50–60% baseline). No grade 4 events or treatment-related deaths were observed. Neutropenia occurred in 22.4% (any grade) and 11.2% (grade ≥3), lower than reported baselines (30–40% and 15–25%, respectively). Among 12 progressors, 75% showed local-only progression without new distant metastases. QoL was stable or improved in 83.9% (function) and 90.3% (health). ETA-guided therapy achieved a cost per month of PFS of ~$6k–10k, compared with $10k–25k for sequential standard-of-care monotherapy. Reduced neutropenia translated into an estimated $24k–48k cohort-level cost avoidance. Metastatic containment (2.4% new distant metastases) mitigated the 2–3× cost escalation associated with multi-organ progression. A single ETA profile ($5k–8k) replaces multiple sequential single-gene tests ($500–2k per test). Achievement of 90.5% disease control and QoL preservation—critical outcomes in palliative refractory cancer—aligns with emerging value-based palliative care frameworks prioritizing quality-adjusted survival. Conclusions: ETA-guided personalized therapy achieves superior efficacy, toxicity control, and putatively cost-effective outcomes by reducing failed treatment sequences, preventing chemotherapy-dose-reducing complications, avoiding febrile neutropenia, limiting metastatic dissemination, and preserving quality of life. Integration into refractory cancer management may provide clinically superior and economically justifiable value in healthcare systems facing escalating metastatic cancer costs.