Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board

Abstract

Purpose Tumor genomic profiling for personalized oncology therapy is being widely applied in clinical practice even as it is being evaluated more formally in clinical trials. Given the complexities of genomic data and its application to clinical use, molecular tumor boards with diverse expertise can provide guidance to oncologists and patients seeking to implement personalized genetically targeted therapy in practice. Methods A multidisciplinary molecular tumor board reviewed tumor molecular profiling reports from consecutive referrals at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins over a 3-year period. The tumor board weighed evidence for actionability of genomic alterations identified by molecular profiling and provided recommendations including US Food and Drug Administration–approved drug therapy, clinical trials of matched targeted therapy, off-label use of such therapy, and additional tumor or germline genetic testing. Results One hundred fifty-five patients were reviewed. Actionable genomic alterations were identified in 132 patients (85%). Off-label therapies were recommended in 37 patients (24%). Eleven patients were treated off-label, and 13 patients were enrolled onto clinical trials of matched targeted therapies. Median progression-free survival of patients treated with matched therapies was 5 months (95% CI, 2.9 months to not reached), and the progression-free survival probability at 6 months was 43%(95% CI, 26% to 71%). Lack of locally available clinical trials was the major limitation on clinical actionability of tumor profiling reports. Conclusion The molecular tumor board recommended off-label targeted therapies for a quarter of all patients reviewed. Outcomes were heterogeneous, although 43% of patients receiving genomically matched therapy derived clinical benefit lasting at least 6 months. Until more data become available from precision oncology trials, molecular tumor boards can help guide appropriate use of tumor molecular testing to direct therapy.

Feasibility of next-generation sequencing in clinical practice: results of a pilot study in the Department of Precision Medicine at the University of Campania ‘Luigi Vanvitelli’

“…[9][10][11][12] Considering the time of follow-up of our study (in most of patients F1CDx was performed in the last 6 months of the study), and the fact that many patients did not progress to their ongoing therapies, probably we will reach this percentage during next years. Indeed, a good number of prospective [17][18][19][20][21][22][23] and retrospective [24][25][26][27] trials evaluated CGP using different techniques (NGS, WES, WGS) but in the context of large academic centres. Largest prospective study defined the potential and the limitations of extensive genomic panel (SHIVA, 17 NCI-MATCH, 18 NCI-MPACT, 19 ASCO-TAPUR, 20 I-PREDICT, 21 WINTHER, 22 PROFILER.…”

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

“…It is reported that of the 59.4%-85% of patients with actionable gene aberrations, only 13.3%-24% received molecular targeted therapy. 2,3 We previously reported that only 10% of pancreatic cancer patients who underwent a targeted amplicon exome sequencing for 160 cancer-related genes (PleSSision-160) could be treated with therapeutic agents based on the results of genomic testing. 4 Clinical sequencing for ovarian cancer is necessary due to its poor prognosis; however, reports regarding ovarian cancer are scarce.…”

Variant classification in precision oncology

“…During the last few years, the use of diagnostic genetic analyses of tumor samples has markedly expanded, facilitating the growth of precision oncology through the identification of a continuously increasing number of therapeutic targets and molecularly defined stratification of patients . Panel‐based next‐generation sequencing (NGS) for the detection of tumor‐specific somatic mutations is already widely available in routine clinical use and a number of bioinformatics tools have been developed for their assessment, including data quality, which is paramount for all subsequent steps (for summaries of these tools see Refs.…”