Likelihood of benefit from large panel genetic profiling in a community hospital system.
Authors: Ciuro Jordan Alana , Hammad Nour , Lyons Susan Elizabeth , Forman Adam Matthew , Bloom Robert Eric 
Published: June 2021

e15025 Background: Cancers have genomic mutations which drive their malignant phenotype. It has been the dream of precision oncology to identify each principal driving mutation, administer therapy directed at a specific defect and thereby provide the most clinical benefit with least toxicity. Previous reports have emphasized the likelihood of finding a targetable mutation in advanced malignancies, however we question the degree of benefit seen in genomic profiling in community-based hospital systems. There are many hurdles to translating mutations into actual real-world benefit, and the effectiveness of commercial profiling is unknown. Methods: This study reviewed data collected by a Michigan Medical Community Cancer Center from 2003 to 2019. We completed a retrospective chart analysis on patients diagnosed with metastatic malignancies who completed genomic profiling with Tempus or Caris. The amount of benefit and cost efficacy were calculated. Results: A total of 102 patients completed genomic sequencing. Age, diagnosis, date of diagnosis, previous lines of therapy, type of next generation sequencing testing (NGS), molecular targets, and outcomes were recorded. Of the 102 individuals, 19 (18.6%) were referred to a clinical trial and 6 of the referred subjects (5.9%) were eligible and entered trials. Two individuals displayed a clinical response by CT imaging. Both were partial remissions lasting 161 and 56 days. An additional 13 patients (12.7%) had either identified mutational targets or high tumor mutational burden (TMB) which altered their therapies outside of a trial. With the addition of targeted agents, 4 patients (3.9%) displayed clinical benefit. Two of these patients had gastric and endometrial carcinoma with high TMB and were placed on immunotherapy. They experienced 638 and 465 days, respectively, of stable disease with partial response. One patient with breast cancer had an androgen receptor and a progression free survival (PFS) of 310 days on enzalutamide. Another breast cancer patient had a PIK3CA mutation with PFS of 131 days on alpelisib. Based on these results, the calculated price for testing alone was $94,817 for every year of PFS obtained, 63% obtained from immunotherapy in two patients with high TMB. The impact of PFS on the OS and cost per quality life-year could not be calculated from this data. Conclusions: These results are in concordance with the magnitude of targetable mutations seen in other publications. However, it brings into question the clinical benefit of NGS panels in a community hospital system. Genomic sequencing aids in the gathering of genetic information, however, at this time there appears to be little change in overall survival for most patients with advanced malignancies. We acknowledge that this is a moving target, and that the usefulness of NGS panels will improve as more treatments are developed. Future studies are needed to help understand the role of NGS at any given point of time.