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

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.

Making the Most of Complexity to Create Opportunities: Comprehensive Genomic Profiling and Molecular Tumor Board for Patients with Non-Small Cell Lung Cancer (NSCLC)

“…In conclusion, objective data are consistent with the indication that patients with advanced/metastatic disease often have distinct molecular alterations that may require matched treatments rather than standard therapies derived from non-biomarker-based populations [ 29 , 30 ]. In this setting, molecular tumor boards can be valuable tools to support a patient’s tailored treatment.…”

“…However, drug accessibility may represent a crucial barrier, thus, clinical and hospital pharmacists should be involved in MTB to facilitate drug administration, even in expanded access programs or in compassionate use. Indeed, only by receiving personalized treatments can the improvement of patient survival associated with the CGP approach be achieved [ 27 , 28 , 29 ].…”

Comprehensive tumor molecular profile analysis in clinical practice

“…Thus, the results obtained must be appropriately comprehended and adopted for the designation of the treatment selection strategy, which can be achieved through inter-discipline collaboration. To this regard, of great use would be the presence of a multidisciplinary Molecular Tumor Board that could assist in the accurate interpretation of the findings obtained from such complex NGS analysis and provide therapeutic recommendations based on all available clinical data for each individual patient [ 100 – 102 ].…”

Targeting G1/S phase cell-cycle genomic alterations and accompanying co-alterations with individualized CDK4/6 inhibitor–based regimens

“…Patients were generally matched after presentation to a Molecular Tumor Board ( 36 – 38 ). Some patients were navigated to prospective precision studies, such as I-PREDICT ( 28 ).…”