Pan-cancer molecular tumor board experience with biomarker-driven precision immunotherapy

Area of Science:

• Oncology
• Genomics
• Immunotherapy

Background:

• Most advanced cancer patients do not benefit from immune checkpoint blockade (ICB).
• Tumor/immune/genome interactions are complex and may limit ICB efficacy.
• N-of-One therapies aim to personalize treatment for refractory cancers.

Purpose of the Study:

• To evaluate the impact of a multidisciplinary Molecular Tumor Board (MTB) on N-of-One therapy selection and patient outcomes.
• To assess the correlation between molecular profile matching and clinical benefit in advanced cancer patients receiving ICB.
• To identify factors associated with improved survival in patients treated with precision medicine strategies.

Main Methods:

• Implementation of a multidisciplinary MTB to review multi-omic cancer data.
• Selection of 80 advanced, refractory cancer patients who received ICB based on MTB recommendations.
• Analysis of the degree of matching between tumor molecular characteristics and administered therapy (Matching Score).
• Comparison of progression-free survival (PFS), overall survival (OS), and clinical benefit rates (CBR) between high and low Matching Score groups.

Main Results:

• 75% of patients had a high degree of matching (≥50%) between tumor molecular profiles and therapy.
• Patients with high Matching Scores had significantly longer median PFS (6.4 vs. 3.0 months) and OS (15.3 vs. 4.7 months).
• Higher clinical benefit rates were observed in the high Matching Score group (53% vs. 21%).
• Only the degree of matching and patient age independently correlated with outcomes; individual biomarkers did not.

Conclusions:

• A precision medicine strategy using an MTB to match therapies, including ICB, to molecular profiles in advanced cancers is associated with improved clinical outcomes.
• The degree of molecular matching, not the number of drugs or specific biomarkers, is a key predictor of treatment success.
• MTBs can facilitate personalized treatment approaches for refractory cancers, enhancing efficacy of therapies like ICB.