Molecular Tumor Board for Unicorns: Outcomes for rare and ultra-rare cancers using an N-of-One personalized treatment strategy.

Treatment of rare/ultra-rare tumors is an unmet need due to a lack of standardized therapies and clinical trials. We developed the Molecular Tumor Board (MTB), a multidisciplinary team that integrates molecular profiling to generate personalized, N-of-One treatments for advanced cancers. This study evaluates 112 patients with rare/ultra-rare tumors who presented to the MTB and were evaluable for clinical therapeutic outcome. Overall, 46/112 patients (41%) received a treatment regimen with a high degree of matching between tumor molecular alterations and drugs given (reflected by a high Matching Score (≥50%)). Patients with a high versus low Matching Score experienced significantly longer progression-free survival ( = 0.005) and overall survival ( = 0.047), and higher rates of clinical benefit (stable disease ≥6 months, partial response, or complete response) (54% vs. 32%  = 0.027). The MTB facilitated personalized N-of-One matching of drugs to tumor molecular alterations, which was associated with improved clinical outcomes in patients with rare/ultra-rare cancers.