CHICAGO—The rapid proliferation of targeted therapies has revolutionized cancer care, bringing truly personalized treatment ever closer.
Limited access to and use of genomic sequencing, however, has kept many patients from using new medications that could work well for them and exposed others to drugs that have significant side effects without corresponding benefits based on their tumor type.
Research presented on June 1 at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago by VA investigators demonstrated that “implementation of precision oncology into clinical practice is feasible across the diverse VHA system,” which serves a higher percentage of rural patients than the national average.1
Researchers at the Durham, NC, VAMC led the study, which assessed the ability of the VA’s National Precision Oncology Program to affect treatment decisions. The Precision Oncology Program was designed to increase use of precision oncology and to standardize its practice.
As part of the program, 3,713 tumor or peripheral blood specimens were collected from veterans at who had solid tumors for which targeted or immunotherapeutic drugs have been developed and who would be eligible for treatment. Seventy-two VA facilities collected samples between July 2016 and June 2018.
Two commercial laboratories performed next-generation sequencing of the specimens using cancer gene panels; 86% of the specimens were successfully sequenced. Both the laboratories and IBM Watson for Genomics generated annotated results of the sequencing.
Men with lung, prostate or colorectal cancers provided the bulk of the specimens. One-third of the samples came from patients in rural areas.
More than 70% of specimens had at least one actionable mutation. Analysis found that the most commonly mutated genes were TP53, ATM and KRAS, and the most frequently recommended therapies were immune checkpoint inhibitors, EGFR kinase inhibitors and PARP inhibitors.
Based on the results, physicians recommended clinical trials for more than half of the veterans. Consequently, the researchers noted that precision oncology was feasible and highlighted “the importance of increasing the availability of clinical trials for veterans.”
In a related ASCO study that also included the University of Washington in Seattle, VA researchers heralded the progress in understanding molecular changes in advanced prostate cancer, saying that “has led to promising precision oncology opportunities; to date, most have been concentrated at tertiary research centers and urban centers and unequally available to patients.”2
The report pointed out that the VHA is the largest integrated healthcare system in the United States and provides medical care to more than six million veterans, about 40% living in rural areas.
VHA patients with advanced stage cancers were offered targeted NGS gene panels (Personalis ACE Extended Cancer Panel; PGDx CancerSELECT/PlasmaSELECT) as part of clinical care.
The study team discussed how 372 veterans from 81 sites underwent NGS sequencing of their prostate tumors, 311, or cfDNA, 61. Results indicated that tumors from 165 (44%) were found to have mutations (allelic ratio ≥5%) in 47 genes.
Also, of the 372, 62 harbored mutations in TP53 (17%), 9 in NOTCH1 (2%), 16 in PTEN (4%), 16 in AR (4%), 13 in ATM (4%), 11 in BRCA2 (3%), 2 in MSH2 (0.5%), 1 in NBN (0.3%) and 1 in PALB2 (0.3%).
Researchers noted that seven men (1.8%) had adequate tumor but no identifiable somatic mutations.
“The VA NPOP has been successfully implemented, and prostate tumors from veterans were found to carry potentially actionable mutations, including BRCA2 and ATM, for which there are precision treatment trials,” study authors wrote. “The program will be expanded and will facilitate more diverse and equitable distribution of access to precision oncology diagnostics and therapeutic opportunities, in alignment with the Cancer Moonshot Initiative.”
1 Poonen P, Duffy J, Hintze BJ, Shukla M, Brettin TS, et al. Genomic analysis of metastatic solid tumors in veterans: Findings from the VHA National Precision Oncology Program. J Clin Oncol 37, 2019 (suppl; abstr 3074).
2 Sokolova A, Cheng HH, Bradley JH, Kelley, M, et. Al. The Veterans Health Administration Precision Oncology Program for Advanced Prostate Cancer Patients: Expanding tumor NGS opportunities to a broader patient population.Journal of Clinical Oncology 2019 37:7_suppl, 193-193. Abstr 193.