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Background: Little is known regarding the rate and clinical outcomes of asymptomatic carriers of SARS-CoV-2 among patients with cancer. Detection of asymptomatic carriers is important in this population given the use of myelosuppressive and immunomodulating therapies. Understanding the asymptomatic carrier rate will help to develop mitigation strategies in this high-risk cohort. Methods: Retrospective cohort analysis of an asymptomatic screening protocol which required patients receiving infusional anti-cancer therapy to undergo a symptom/exposure screen and SARS-CoV-2 PCR testing 24-96 h prior to their infusion. The primary outcome of this analysis was the rate of asymptomatic SARS-CoV-2 infection. Secondary outcomes included the rate of COVID-19-related hospitalization and mortality and delays in oncologic therapy. Results: Among a cohort of 2691 cancer patients who underwent asymptomatic screening, 1.6% (N = 43/2691) of patients were found to be SARS-CoV-2 positive on asymptomatic screening. 11.6% (N = 5/43) of the cohort ultimately developed COVID-19-related symptoms. Four patients required hospitalization for complications of COVID-19 infection. No patient died from COVID-related complications. 97.7% (N = 42/43) had their anti-cancer therapy delayed or deferred with a median delay of 21 days (range: 7-77 days). Conclusions: Overall, among a cohort of active cancer patients receiving anti-cancer therapy, an asymptomatic SARS-CoV2 PCR-based screening protocol detected a small cohort of asymptomatic carriers. The majority of these patients remained asymptomatic on long-term follow-up and outcomes were much more favorable compared to previously described outcomes of cancer patients with symptomatic COVID-19 infection. [ABSTRACT FROM AUTHOR]

The pancreas is a rare site of metastasis in renal cell carcinoma and little is known regarding the prognostic significance of pancreatic metastases (PM) in renal cell carcinoma. We analyzed 4736 patients with advanced renal cell carcinoma to assess the effect of PM on outcomes. PM was associated with superior overall and progression-free survival compared with patients without PM. Background: Pancreatic metastases (PM) are rare in renal cell carcinoma. It has been suggested that patients with metastases to the pancreas have a more favorable prognosis, but little is known about the long-term outcomes with systemic therapy. We sought to understand the outcomes of patients with metastatic renal cell carcinoma with PM treated with systemic therapy. Patients and Methods: We conducted a pooled analysis of 4736 patients with metastatic renal cell carcinoma treated on phase II/III clinical trials. Systemic therapies included anti-vascular endothelial growth factor targeted therapy, mammalian target of rapamycin-targeted therapy, and cytokine therapy. Results: The primary end point was overall survival (OS) in patients with versus without PM. Statistical analyses were performed using Kaplan-Meier analysis and Cox regression. Among 4736 patients, 235 (5.0%) were identified to have baseline PM at therapy initiation. The median OS in patients with PM was significantly prolonged with OS of 41.7 months versus 19.0 months (adjusted hazard ratio, 0.52; P < .0001). Similarly, progression-free survival was significantly prolonged in patients with PM (10.9 vs. 6.9 months; adjusted hazard ratio, 0.72; P = .004). The effect of PM on OS and progression-free survival was independent of other sites of metastasis or International mRCC Database Consortium risk group. Conclusion: The presence of PM in RCC is an independent positive predictor for survival and improved response to systemic therapy. These findings suggest RCC with PM is associated with favorable outcomes and further work to understand the underlying disease biology of these patients is warranted. [ABSTRACT FROM AUTHOR]

In advanced prostate cancer, circulating tumor (ctDNA) has been increasingly used for genomic sequencing. We examined the real-world use of commercial ctDNA assays among a cohort of patients with metastatic castrate resistant prostate cancer (mCRPC) and assessed the ctDNA genomic landscape, rate of actionable alterations, and the correlation of ctDNA characteristics with survival. We found that ctDNA detected pathogenic alterations in most patients and the number of detected alterations was strongly associated with inferior overall survival. Background: There has been considerable interest in ctDNA next generation sequencing platforms to assess genomic alterations in mCRPC given its accessibility and identification of temporal genomic data. Patientsand Methods: In this retrospective analysis, we analyzed 63 patients who underwent ctDNA genomic profiling during their mCRPC disease course using a CLIA-certified commercial assay. The primary objective was to assess the feasibility of commercial ctDNA analysis in a real world mCRPC cohort. Key secondary objectives included assessment of the landscape of pathogenic ctDNA alterations and the prognostic significance of ctDNA detection on overall survival (OS). Results: Among the cohort, at the time of ctDNA collection, median age was 70 years, and 47.6% (N = 30/63) had bone-only metastases. ctDNA was detected in the majority of patients with at least 1 pathogenic alteration detected in 90.5% (N = 57/63) of individuals. The most common alterations detected were in AR, TP53, and PIK3CA. Actionable alterations with FDA-approved therapies were found in 15.8% (N = 10) of the cohort. The presence of = 1 versus > 1 alteration on ctDNA analysis was strongly associated with inferior OS with a median OS of 26.1 versus 8.8 months, respectively (HR = 7.0, 95% CI, 2.2-23.1, P < .001). In multivariate analysis, the number of detected alterations remained a significant predictor for OS. Lastly, there was weak correlation between Prostate-Specific Antigen (PSA), and ctDNA characteristics. Conclusion: ctDNA is a viable next generation sequencing (NGS) platform in mCRPC and can be utilized to identify actionable alterations. The presence and extent of ctDNA alterations appear to be prognostic of OS in mCRPC. [ABSTRACT FROM AUTHOR]

Data regarding the clinical outcomes of men with metastatic hormone sensitive prostate cancer (mHSPC) who harbor homologous recombination repair (HRR) gene alterations have not been fully characterized. Here, we examine a cohort of mHSPC patients who underwent genomic sequencing to evaluate the impact of HRR gene alterations on time to castrate resistance and other outcomes. We found that the presence of an HRR gene alteration is associated with a shorter time to mCRPC. Introduction: The homologous recombination repair (HRR) pathway is a frequently mutated pathway in advanced prostate cancer. The clinical course of patients with HRR gene alterations who have metastatic hormone sensitive prostate cancer (mHSPC) has not been fully characterized. Here, we examine the outcomes of men with mHSPC with HRR alterations. Methods: We conducted a single-center retrospective analysis of men with mHSPC who underwent next generation sequencing. The primary objective was to assess the time from diagnosis of mHSPC to metastatic castrate resistance prostate cancer (mCRPC) in patients with pathogenic HRR alterations compared to individuals lacking these alterations. Key secondary objectives included time to mCRPC in prespecified cohorts, PSA response, and overall survival. Results: 151 men with mHSPC were identified for the study. 24% (N = 37) had pathogenic HRR gene alterations detected with the most common alterations found in BRCA2 (n = 15), ATM (n = 10), and CDK12 (n = 7). Time to mCRPC was significantly decreased in patients with HRR gene alterations versus those without such alterations (12.7 vs. 16.1 months, HR 1.95, P = .02). In multivariate analysis, the effect of HRR gene alterations on time to CRPC remained significant when adjusting for age, mHSPC therapy, the volume of disease, the presence of visceral metastases, and PSA (adjusted HR 1.69, P = .02). Stratified by specific HRR gene alteration, patients with BRCA2 or CDK12 had significantly decreased time to mCRPC compared to other HRR alterations. Conclusion: HRR gene alterations are associated with the worse outcomes in mHSPC with significantly shorter time to mCRPC. Given the established role of Poly (ADP-ribose) Polymerase (PARP) inhibitors in mCRPC, these data highlight an opportunity to examine PARP inhibitors earlier in the clinical course for prostate cancer patients. Ongoing prospective studies will further validate the role of PARP inhibitors in mHSPC patients. [ABSTRACT FROM AUTHOR]

Background: CDK12 inactivation leading to increased neoantigen burden has been hypothesized to sensitize tumors to immune checkpoint inhibition. Pan‐cancer data regarding the frequency of CDK12 alterations are limited. We aimed to characterize CDK12 alterations across all cancer types through real‐world clinical‐grade sequencing. Methods: This was a single‐center retrospective analysis of 4994 cancer patients who underwent tissue or blood genomic profiling, including CDK12 assessment, conducted as part of routine care from December 2012 to January 2020. Prevalence, clinical characteristics, and treatment outcomes of patients with tumors with pathogenic CDK12 alterations were described. Results: In all, 39 (0.78%, n = 39/4994) patients had pathogenic CDK12 alterations. Among CDK12‐altered tumors, the most common organ site was prostate (n = 9, 23.1%) followed by colorectal (n = 5, 12.8%). Adenocarcinoma was the most common histology (n = 26, 66.7%). Median follow‐up from time of diagnosis was 4.02 years. Median overall survival from time of metastasis was 4.43 years (95% CI: 3.11–5.74). Ten patients with CDK12‐altered tumors received at least one immune checkpoint inhibitor‐containing regimen. The majority of patients (n = 6/10, 60%) experienced an objective response. Progression‐free survival for patients who had metastatic disease and received a checkpoint inhibitor‐containing regimen was 1.16 years (95% CI: 0.32–2.00). Conclusion: CDK12 alterations are rare events across hematologic and solid tumor malignancies. They represent a clinically distinct molecular cancer subtype which may have increased responsiveness to checkpoint inhibition. Prospective studies are warranted to investigate checkpoint inhibition in CDK12‐altered tumors. [ABSTRACT FROM AUTHOR]