Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers

Abstract

OBJECTIVE To determine the feasibility and clinical utility of using comprehensive genomic profiling (CGP) in the course of clinical care to identify clinically relevant tumor genomic alterations for patients with either rare or refractory gynecologic cancers to facilitate point-of-care management. Use of an expert, multidisciplinary, institutional molecular tumor board (MTB) assessment is discussed regarding input on putative targeted options for individualized therapy. METHODS A prospective clinical trial is ongoing. We report on the initial 69 patients with gynecologic cancers that were either rare or refractory to standard therapy. CGP was performed by Foundation Medicine, Inc. Genomic alterations were reviewed by members of an MTB. Consensus recommendations on genomically targeted, FDA-approved, on- and off-label therapies and clinical trials were sent to the treating physician, and decisions and outcomes were assessed. RESULTS Study outcomes were available for 64 patients. The mean number of genes altered per tumor was 4.97 (median=4; range, 1–26), and the average turnaround time from testing laboratory report to generation of formal recommendations was approximately three weeks. Evaluation of genomic and clinical data by the MTB led to generation of targeted treatment options in all 64 patients, and the percentage of patients for whom one or more of these recommendations were implemented by the treating physician was 39%. Seventy percent of the patients receiving targeted therapy based on a CGP result experienced radiologic response or showed evidence of clinical benefit or stable disease. CONCLUSION These data suggest that an institutional MTB is a feasible venue for reviewing tumor genomic profiling results and generating clinical recommendations. These data also support the need for further studies and guidelines on clinical decision making with greater availability of broad genomically based diagnostics.

Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

“…Notable exceptions were higher HRD scores associated with better clinical outcomes in GBM and OV ( Figure 3C ), and with overall survival in OV ( Figures S7B and S7C ). This may reflect the use of potent, DNA-damaging platinum-based compounds as standard-of-care therapy for OV ( Figure S7 ) ( Mills et al, 2016 ). The association of a higher HRD score with better outcomes in GBM may be linked to IDH mutations.…”

Tumor Mutational Burden Guides Therapy in a Treatment Refractory POLE-Mutant Uterine Carcinosarcoma

“…Although standard MSI testing captures the nearly 28% of endometrial cancers that are MSI‐H, patients with high TMB and MSS tumors because of POLE ‐mediated mechanisms (7%) and others go undetected , and thus potentially relevant treatment options remain unexplored. A recent analysis suggests that genomic profiling aids in clinical decision‐making in gynecologic cancers .…”

Precision Medicine: Implications for Science and Practice

“…The authors concluded that broad implementation of multiplex hotspot testing is feasible but that only a small portion of the patients with cancer characterized by actionable alterations were actually enrolled onto genotype-matched trials. Other studies on smaller populations have provided support for the ability of comprehensive tumor genomic profiling to direct the point-of-care management of patients with cancer, (10,11) although the percentage of patients subsequently enrolled in genotype-matched clinical trials was similarly low (10).…”

“…To increase the number of feasible therapeutic options recommended for patients undergoing broad-based genomic sequencing, many center-wide efforts have been initiated (9)(10)(11)(12)(13). These often recommendations to the referring physician in a point-of-care manner, and subsequent follow up of patient outcomes.…”

“…These often recommendations to the referring physician in a point-of-care manner, and subsequent follow up of patient outcomes. In some cases, this process is conducted in the setting of a prospective, observational clinical trial approved by an institutional review board (9)(10)(11). The importance of carrying out these efforts at an academic medical center is highlighted by the depth of expertise required at every step along the way, including tumor tissue acquisition, assessment, and processing; genomic profiling and analysis; molecular tumor board review; clinical care and translational research performed by core personnel; data acquisition; and outcome assessment.…”