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Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy.

  • Author(s): 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
  • et al.
Abstract

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.

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