Abstract
OBJECTIVES:With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer.METHODS:We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy.RESULTS:From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months.CONCLUSION:We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.
Highlights
The enhancement of molecular biology techniques in the past decades and the subsequent understanding of cell-cycle control mechanisms have helped to define the hallmarks of cancer and initiate the era of targeted therapy [1,2]
The development of imatinib for the treatment of patients with chronic myeloid leukemia has led to an impressive improvement in the clinical management of this disease, initiating a race to develop and clinically test small-molecule inhibitors and monoclonal antibodies targeting fundamental effectors involved in cell carcinogenesis [3,4]
Among the 28 patients excluded from the analysis, 19 patients were lost to follow-up or had no data on treatment after the completion of the genomic sequencing test, 6 patients received targeted therapy considered standard for the respective histology, and 3 patients were younger than 18 years old
Summary
The enhancement of molecular biology techniques in the past decades and the subsequent understanding of cell-cycle control mechanisms have helped to define the hallmarks of cancer and initiate the era of targeted therapy [1,2]. Next-generation sequencing (NGS) is one of the most advanced technologies applied to deciphering molecular alterations in tumors and enables scientists to rapidly identify numerous mutations in patient tumors [5,6,7]. This growing knowledge has significantly improved pharmaceutical development over the years, leading to some impressive successes in cancer care [1,2]
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