Precision medicine‐based therapies in advanced colorectal cancer: The University of California San Diego Molecular Tumor Board experience

Abstract

Treatment for advanced colorectal cancer is often limited by complex molecular profiles, which promote resistance to systemic agents and targeted monotherapies. Recent studies suggest that a personalized, combinatorial approach of matching drugs to tumor alterations may be more effective. We implemented a precision medicine strategy by forming a Molecular Tumor Board (MTB), a multidisciplinary team of clinicians, scientists, bioinformaticians and geneticists. The MTB integrated molecular profiling information and patient characteristics to develop N-of-One treatments for 51 patients with advanced colorectal cancer. All patients had metastatic disease and 63% had received ≥ 3 prior therapy lines. Overall, 34/51 patients (67%) were matched to ≥ 1 drug recommended by the MTB based on individual tumor characteristics, whereas 17/51 (33%) patients received unmatched therapies. Patients who received matched therapy demonstrated significantly longer progression-free survival (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21-0.81; P = 0.01) and a trend towards higher clinical benefit rates (41% vs. 18%, P = 0.058) (all multivariate) compared to patients receiving unmatched therapy. The MTB facilitated personalized matching of drugs to tumor characteristics, which was associated with improved progression-free survival in patients with advanced colorectal cancer.

The impact of the multi-disciplinary molecular tumour board and integrative next generation sequencing on clinical outcomes in advanced solid tumours

“…This corresponds with other findings that the MTB could improve treatment decisions and patient management. 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 …”

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer: Unravelling challenges and future directions

“…Strategies for overcoming resistance include developing combination therapies that target multiple pathways, repurposing existing drugs, and developing novel agents to evade resistance mechanisms. Precision medicine approaches such as tumor molecular profiling and real-time monitoring facilitate the early detection of resistance mechanisms, allowing prompt adjustments to treatment strategies[ 193 , 194 ]. Furthermore, biomarker research in CRC is rapidly evolving with the aim of identifying molecular signatures crucial for diagnosis, prognosis, and treatment decisions.…”

Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors

“…Previous studies have explored the use of MTBs in breast [ 6 ], colorectal [ 7 ], esophageal [ 8 ], gynecological [ 9 ], head and neck [ 1 ], lung[ 10 ], upper-gastrointestinal [ 11 ], and urological [ 12 ] cancers, as well as in other mixed cancer cohorts [ 13 , 14 ]. Their role in neuro-oncology has been explored in recent publications.…”