Abstract CT133: The impact of gene panel sequencing on clinical care in patients with cancer

Abstract

Abstract Introduction: Analysis of tumors for somatic mutations of individual cancer-associated genes has proven valuable in defined clinical scenarios, but the incorporation of multi-gene panels into routine clinical use has proven complex. Here, we describe UNCseq™, a single-institution experience evaluating how care providers use testing of a 247 gene panel in a study of >1400 patients with cancer. Approach: Somatic and germline DNA was captured and sequenced in the context of an IRB-approved clinical trial, with somatic events (point mutations (PM) and copy number alterations (CNA)) determined using an institution-designed bioinformatic pipeline. Mutations deemed ‘actionable’ by a molecular tumor board (MTB) were confirmed in a CLIA-compliant manner, and reported to the patient's caregiver. The clinical use of sequencing information by caregivers was determined through follow-up questionnaire. Results: Somatic events were noted in 444 of 718 (62%) patients as of 11/30/2014 (79% PM/21% CNA). Although 247 genes were analyzed, reports were only made regarding a minority (77) of genes. PMs of PIK3CA/PTEN/KRAS/BRAF/PIK3R1 and CNAs of CCDN1/EGFR/ERBB2/FGFR1 were the most commonly reported events. Non-canonical (71%) events were observed more frequently than canonical events (29%, p<0.05). Among 30 tumor types, events were most commonly noted in uterus, (n = 75, 17%) colorectal, (n = 37, 8%) and bladder (n = 31, 7%), and most infrequently noted in kidney (n = 13, 3%) and soft-tissue sarcoma (n = 7, 2%). Healthcare providers reported changes in clinical care based on mutations discovered through UNCseq™ in 15% of patients. Caregivers reported changes primarily in therapy (e.g. trial enrollment, prescription of targeted kinase inhibitors) and prognosis (e.g. HPV status put the patient in a more favorable prognostic category) based on UNCseq™ results. Care was not changed in many patients, despite their tumor harboring an actionable event(s), because of: i) inappropriate clinical stage, ii) patient dying prior to or soon after results, iii) inability to procure indicated therapy because of payment issues or sub-optimal clinical trials design or iv) patient lost to follow up. The cost is comparable to other molecular testing such as fluorescence in-situ hybridization of HER2 done clinically. Conclusions: An analysis of 247 genes for somatic mutations in patients with advanced cancer is cost-effective and feasible, and can lead to significant changes in clinical care in a minority of patients. Non-canonical events are common, and determination of events for reporting requires pathological review by an MTB. Patients with advanced disease and certain tumor types benefit most from cancer panel sequencing. A majority of patients harbor actionable events, although changes in therapeutic care are less frequent largely because of practical considerations related to care delivery. These data suggest a need to re-structure clinical trials in the era of modern genomic testing. Citation Format: David Neil Hayes, Juneko E. Grilley-Olson, David A. Eberhard, Nirali M. Patel, Joel S. Parker, Karen E. Weck, William Y. Kim, Michele C. Hayward, H. Shelton Earp, Norman E. Sharpless. The impact of gene panel sequencing on clinical care in patients with cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT133. doi:10.1158/1538-7445.AM2015-CT133