- Kato, Shumei;
- Kim, Ki Hwan;
- Lim, Hyo Jeong;
- Boichard, Amelie;
- Nikanjam, Mina;
- Weihe, Elizabeth;
- Kuo, Dennis J;
- Eskander, Ramez N;
- Goodman, Aaron;
- Galanina, Natalie;
- Fanta, Paul T;
- Schwab, Richard B;
- Shatsky, Rebecca;
- Plaxe, Steven C;
- Sharabi, Andrew;
- Stites, Edward;
- Adashek, Jacob J;
- Okamura, Ryosuke;
- Lee, Suzanna;
- Lippman, Scott M;
- Sicklick, Jason K;
- Kurzrock, Razelle
Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated a multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, and physicians from multiple specialties) molecular tumor board (MTB), which included a project manager to facilitate obtaining clinical-grade biomarkers (blood/tissue NGS, specific immunohistochemistry/RNA expression including for immune-biomarkers, per physician discretion) and medication-acquisition specialists/clinical trial coordinators/navigators to assist with medication access. The MTB comprehensively reviewed patient characteristics to develop N-of-One treatments implemented by the treating physician's direction under the auspices of a master protocol. Overall, 265/429 therapy-evaluable patients (62%) were matched to ≥1 recommended drug. Eighty-six patients (20%) matched to all drugs recommended by MTB, including combinatorial approaches, while 38% received physician's choice regimen, generally with unmatched approach/low degree of matching. Our results show that patients who receive MTB-recommended regimens (versus physician choice) have significantly longer progression-free (PFS) and overall survival (OS), and are better matched to therapy. High (≥50%) versus low (<50%) Matching Score therapy (roughly reflecting therapy matched to ≥50% versus <50% of alterations) independently correlates with longer PFS (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50-0.80; P < 0.001) and OS (HR, 0.67; 95% CI, 0.50-0.90; P = 0.007) and higher stable disease ≥6 months/partial/complete remission rate (52.1% versus 30.4% P < 0.001) (all multivariate). In conclusion, patients who receive MTB-based therapy are better matched to their genomic alterations, and the degree of matching is an independent predictor of improved oncologic outcomes including survival.