Purpose To determine whether cotargeting poly (ADP-ribose) polymerase-1 plus androgen receptor is superior to androgen receptor inhibition in metastatic castration-resistant prostate cancer (mCRPC) and whether ETS fusions predict response. Patients and Methods Patients underwent metastatic site biopsy and were stratified by ETS status and randomly assigned to abiraterone plus prednisone without (arm A) or with veliparib (arm B). Primary objectives were: confirmed prostate-specific antigen (PSA) response rate (RR) and whether ETS fusions predicted response. Secondary objectives were: safety, measurable disease RR (mRR), progression-free survival (PFS), and molecular biomarker analysis. A total of 148 patients were randomly assigned to detect a 20% PSA RR improvement. Results A total of 148 patients with mCRPC were randomly assigned: arm A, n = 72; arm B, n = 76. There were no differences in PSA RR (63.9% v 72.4%; P = .27), mRR (45.0% v 52.2%; P = .51), or median PFS (10.1 v 11 months; P = .99). ETS fusions did not predict response. Exploratory analysis of tumor sequencing (80 patients) revealed: 41 patients (51%) were ETS positive, 20 (25%) had DNA-damage repair defect (DRD), 41 (51%) had AR amplification or copy gain, 34 (43%) had PTEN mutation, 33 (41%) had TP53 mutation, 39 (49%) had PIK3CA pathway activation, and 12 (15%) had WNT pathway alteration. Patients with DRD had significantly higher PSA RR (90% v 56.7%; P = .007) and mRR (87.5% v 38.6%; P = .001), PSA decline ≥ 90% (75% v 25%; P = .001), and longer median PFS (14.5 v 8.1 months; P = .025) versus those with wild-type tumors. Median PFS was longer in patients with normal PTEN (13.5 v 6.7 months; P = .02), TP53 (13.5 v 7.7 months; P = .01), and PIK3CA (13.8 v 8.3 months; P = .03) versus those with mutation or activation. In multivariable analysis adjusting for clinical covariates, DRD association with PFS remained significant. Conclusion Veliparib and ETS status did not affect response. Exploratory analysis identified a novel DRD association with mCRPC outcomes.

Key Points Question What is the clinical utility of genomic profiling for patients with advanced solid tumors? Findings In this cohort study of 1015 patients who underwent integrative genomic profiling, a high rate of pathogenic germline variants and a subset of patients who derive substantial clinical benefit from sequencing information were identified. Meaning These findings support (1) directed germline testing for inherited cancer predisposition in all patients with advanced cancer and (2) use of integrative genomic profiling as a component of standard of care for patients with cancer of unknown origin and other rare malignant neoplasms.

with Aims: Validation of associations for SNPs in RAC2, NCF4 and SLC28A3, identification of a novel association with a TOP2B SNP and screening 23 SNPs putatively relevant to anthracycline-induced cardiotoxicity. Patients & methods: A total of 166 breast cancer patients treated with doxorubicin underwent echocardiogram, including 19 cases with systolic dysfunction (ejection fraction <55%) and 147 controls. Four high priority SNPs were tested in the primary analysis, with appropriate statistical correction, and 23 additional SNPs were screened in an uncorrected secondary analysis. Results: Previously reported associations for RAC2, NCF4 and SLC28A3 could not be validated and a novel association with TOP2B was not discovered in this cohort (all p > 0.05), likely due to inadequate power. Two SNPs were identified in the uncorrected secondary analysis including a protective SNP in ABCB1 (3435C>T, p = 0.049) and a risk allele in CBR3 (V244M, p = 0.012). Conclusion: The associations reported in prior publications and those discovered in this secondary analysis require further replication in independent cohorts.

The Veterans Health Administration system is one of the largest integrated health care providers in the United States, delivering medical care to > 9 million veterans. Barriers to delivering efficient health care include geographical limitations as well as long wait times. Telehealth has been used as a solution by many different health care services. However, it has not been as widely used in cancer care. In 2018, the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System expanded the use of telehealth to provide antineoplastic therapies to rural patients by creating a clinical video telehealth clinic of the Virtual Cancer Care Network. This allows oncologists located at the tertiary center to virtually deliver care to remote sites. The recent COVID-19 pandemic forced oncologists across the VA system to adopt telehealth to provide continuity of care. On the basis of our review and personal experience, we have outlined opportunities for telehealth to play a role in every step of the cancer care journey from diagnosis to therapy to surveillance to clinical trials for medical, surgical, and radiation oncology. There are many advantages, such as decreased travel time and potential cost savings; however, there continues to be challenges with veterans having access to devices and the Internet as well as understanding how to use telehealth equipment. The lessons learned from this assessment of the VA telehealth system for cancer care can be adopted and integrated into other health systems. In the future, there needs to be evaluation of how telehealth can be further incorporated into oncology, satisfaction of veterans using telehealth services, overcoming telehealth barriers, and defining metrics of success.