Leveraging Veterans Health Administration Clinical and Research Resources to Accelerate Discovery and Testing in Precision Oncology
Objective: The promise of precision oncology, which is the ability to choose a treatment specific to the characteristics of the tumor, has arrived. There are targeted therapies based on tumor mutations in multiple cancer types, both approved and in development. The US Department of Veterans Affairs (VA) has embraced precision oncology for the treatment of patients with prostate cancer.
Observations: This article focuses on the efforts to bring precision oncology treatments and trials to veterans with prostate cancer through the Precision Oncology Program for Cancer of Prostate (POPCaP) Centers of Excellence (COE) and the clinical trials consortium inside POPCaP, Prostate Cancer Analysis for Therapy CHoice (PATCH). Through POPCaP, VA has analyzed hundreds of prostate cancer tumors to identify mutations and develop treatment plans for veterans with prostate cancer. PATCH will leverage the genetic data and prostate cancer expertise of POPCaP COEs to develop clinical trials for veterans that take a precision oncology approach to care.
Conclusions: With its extensive resources and capabilities, VA has the ability to advance a precision oncology agenda that provides veterans with the highest standard of care. It has built upon many key elements in clinical, technological and scientific fields of study that would challenge most other health care systems given the extensive costs involved.
Prostate Cancer Analysis
The overall PATCH vision is designed for clinical care and research work to together toward improved care for those with prostate cancer (Figure 1). The resources necessary for successful translational research are substantial, and PATCH aims to streamline those resources. PATCH will support innovative, precision-based clinical research at the POPCaP COEs through its 5 arms.
Arm 1. Dedicated personnel ensure veteran access to trials in PATCH by giving patients and providers accurate information about available trial options; aiding veterans in traveling from home VA to a POPCaP COE for participation on a study; and maintaining the Committee for Veteran Participation in PATCH, where veterans will be represented and asked to provide input into the PATCH process.
Arm 2. Coordinators at the coordinating COE in Portland, Orgeon, train investigators and study staff at the local POPCaP COEs to ensure research can be performed in a safe and responsible way.
Arm 3. Personnel experienced in conducting clinical trials liaise with investigators at VA Central Institutional Review Board, monitor trials, build databases for appropriate and efficient data collection, and manage high-risk studies conducted under an Investigational New Drug application. This group works closely with biostatisticians to choose appropriate trial designs, estimate numbers of patients needed, and interpret data once they are collected.
Arm 4. Protocol development and data dissemination is coordinated by a group to assist investigators in drafting protocols and reviewing abstracts and manuscripts.
Arm 5. A core group manages contracts and budgets, as well as relationships between VA and industry, where funding and drugs may be obtained.
Perhaps most importantly, PATCH leverages the genetic data collected by POPCaP COEs to find patients for clinical trials. For example, the trials that examined olaparib and rucaparib assumed that the prevalence of HRD was about 25% in men with advanced prostate cancer.11 As these trials began enrollment, however, researchers discovered that the prevalence was < 20%. In fact, the study of olaparib screened 4,425 patients at 206 sites in 20 countries to identify 778 (18% of screened) patients with HRD.4 With widespread sequencing within VA, it could be possible to identify a substantial number of patients who are already known to have the mutation of interest (Figure 2).
Clinical Trials
There are currently 2 clinical trials in PATCH; 4 additional trials await funding decisions, and more trials are in the concept stage. BRACeD (NCT04038502) is a phase 2 trial examining platinum and taxane chemotherapy in tumors with HRD (specifically, BRCA1, BRCA2, and PALB2). About 15% to 20% of men with advanced prostate cancer will have a DNA repair defect in the tumor that could make them eligible for this study. The primary endpoint is progression-free survival.
A second study, CHOMP (NCT04104893), is a phase 2 trial examining the efficacy of immunotherapy (PD-1 inhibition) in tumors having mismatch repair deficiency or CDK12-/-. Each of those is found in about 7% of men with metastatic prostate cancer, and full accrual of a trial with rare mutations could take 5 to 10 years without a systematic approach of sequencing and identifying potential participants. The primary endpoint is a composite of radiographic response by iRECIST (immune response evaluation criteria in solid tumors), progression-free survival at 6 months and prostate specific antigen reduction by ≥ 50% in ≤ 12 weeks. With 11 POPCaP COEs sequencing the tumors of every man with metastatic prostate cancer, identifying men with the appropriate mutation is possible. PATCH will aid the sites in recruitment through outreach and coordination of travel.
