Molecular tumor board: the University of California-San Diego Moores Cancer Center experience.

OBJECTIVE: DNA sequencing tests are enabling physicians to interrogate the molecular profiles of patients' tumors, but most oncologists have not been trained in advanced genomics. We initiated a molecular tumor board to provide expert multidisciplinary input for these patients. MATERIALS AND METHODS: A team that included clinicians, basic scientists, geneticists, and bioinformatics/pathway scientists with expertise in various cancer types attended. Molecular tests were performed in a Clinical Laboratory Improvement Amendments environment. RESULTS: Patients (n = 34, since December 2012) had received a median of three prior therapies. The median time from physician order to receipt of molecular diagnostic test results was 27 days (range: 14-77 days). Patients had a median of 4 molecular abnormalities (range: 1-14 abnormalities) found by next-generation sequencing (182- or 236-gene panels). Seventy-four genes were involved, with 123 distinct abnormalities. Importantly, no two patients had the same aberrations, and 107 distinct abnormalities were seen only once. Among the 11 evaluable patients whose treatment had been informed by molecular diagnostics, 3 achieved partial responses (progression-free survival of 3.4 months, ≥6.5 months, and 7.6 months). The most common reasons for being unable to act on the molecular diagnostic results were that patients were ineligible for or could not travel to an appropriately targeted clinical trial and/or that insurance would not cover the cognate agents. CONCLUSION: Genomic sequencing is revealing complex molecular profiles that differ by patient. Multidisciplinary molecular tumor boards may help optimize management. Barriers to personalized therapy include access to appropriately targeted drugs.

Real-World Data From a Molecular Tumor Board: Improved Outcomes in Breast and Gynecologic Cancers Patients With Precision Medicine.

PURPOSE: Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS: Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS: Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS (P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION: Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.

Breast Cancer Experience of the Molecular Tumor Board at the University of California, San Diego Moores Cancer Center.

PURPOSE: Multiplex genomic tests are enabling oncologists to interrogate the DNA of their patients. However, few oncologists are proficient with respect to the implications of complex molecular diagnostics. We initiated a Molecular Tumor Board that focused on individual patients with advanced cancer whose tumors underwent genomic profiling, and here report our experience with breast cancer. METHODS: A multidisciplinary team that included physicians, scientists, geneticists, and bioinformatics/pathway specialists attended. All molecular tests were performed in a Clinical Laboratory Improvement Amendments environment (next-generation sequencing, 182 or 236 genes). RESULTS: Forty of 43 patients (93%; mean age, 59 years) had at least one theoretically actionable aberration (mean, 4.79 anomalies/patient). Median time from ordering to report was 27 days (median of approximately 11 days for specimen acquisition and approximately 14 days for diagnostic processing). Even if we considered distinct abnormalities in a gene as the same, there were only two patients with an identical molecular profile. Seventy-three genes (206 abnormalities; 119 distinct) were aberrant. Seventeen of the 43 patients (40%; median, seven previous therapies in the metastatic setting) were treated in a manner consistent with Molecular Tumor Board discussions; seven (16% of 43, or 41% of 17) achieved stable disease for 6 or more months (n = 2) or partial remission (n = 5). Lack of access to targeted medication was the most common reason that patients could not be treated. CONCLUSION: Multidisciplinary molecular tumor boards may help to optimize the management of patients with advanced, heavily pretreated breast cancer who have undergone genomic testing. Facilitating availability of appropriately targeted drugs and clinical trials is needed.