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Importance: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking., Objective: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer., Design, Setting, and Participants: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022., Exposure: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19., Main Outcomes and Measures: Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up., Results: Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13)., Conclusions and Relevance: In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited., Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF., Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated., Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p <0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], p interaction <0.001)., Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)., Competing Interests: R.M reports research funding from Bayer, Pfizer, and Tempus; and 18 personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, 19 Caris, Dendreon, Exelixis, Janssen, Johnson and Johnson, Merck & Co, Myovant, Novartis, Pfizer, Sanofi, Sorrento Therapeutics, Tempus, and Vividion. A.N. reports consulting fees from AstraZeneca, Takeda Oncology and Bantam Pharmaceuticals. B.B. reports research support to institution from Amgen, Bicycle Therapeutics, Boehringer Ingelheim, Ikena Oncology, Kahr Medical, Merck, Syros, Tarveda Therapeutics. Z.B. receives research support from 10.13039/100004328Genentech/imCORE and Bristol Myers Squibb. Personal fees from UpToDate. L.A.F reports clinical trial funding from BMS, EMDserono, Pfizer, Merck, Array, Kartos, Incyte, personal fees from Elsevier, ViaOncology, outside the submitted work. J.L.W. reports research funding from NIH/NCI during the conduct of the work, research funding from AACR, consulting fees from Westat, Roche, Flatiron Health, Melax Tech, other from HemOnc.org LLC (ownership), outside the submitted work. C.H reports stock holdings in Johnson and Johnson; research funding to institution from Merck, Bausch Health, Genentech, Bayer, and AstraZeneca, consultant fees from Tempus, Genzyme, and EMD Sorono, speaking fees from OncLive/MJH Life Sciences, travel fees from Merck, all outside the submitted work. The remaining authors have nothing to disclose., (© 2023 Published by Elsevier Inc.)

Purpose: Intraductal carcinoma of the prostate (IDC-P) is a relatively unstudied feature present in some prostate cancer (PC) diagnoses with several studies suggesting associations with higher Gleason scores (GS) and earlier time to biochemical recurrence (BCR) after definitive treatment. We looked to identify cases of IDC-P in the Veterans Health Administration (VHA) database and measure associations between IDC-P and pathological stage, BCR, and metastases., Methods: Patients in the VHA database diagnosed with PC from 2000 to 2017, treated with radical prostatectomy (RP) at the VHA were included in the cohort. BCR was defined as post-RP PSA >0.2 or administration of androgen deprivation therapy (ADT). Time to event was defined as time from RP to event or censor. Differences in cumulative incidences were assessed through Gray's test. Associations with IDC-P and pathologic features at RP, BCR and metastases were assessed through multivariable logistic and Cox regression models., Results: Of 13,913 patients meeting inclusion criteria, 45 patients had IDC-P. Median follow up was 8.8 years from RP. Multivariable logistic regressions showed patients with IDC-P were more likely to have GS ≥8 (Odds Ratio (OR) 1.14, P = .009) and higher T stages (T3 or 4 vs. T1 or 2 OR 1.14, P < .001). In total, 4,318 patients experienced a BCR, and 1,252 patients developed metastases of whom 26 and 12, respectively, had IDC-P. On multivariable regression IDC-P was associated with higher risk of BCR (IDC-P Hazard Ratio (HR) 1.71, P = .006) and metastases (HR 2.84, P < .001). Cumulative incidence of metastases at 4 years for IDC-P and non-IDC-P were 15.9% and 5.5% (P < .001) respectively., Conclusions: In this analysis, IDC-P was associated with higher Gleason score at RP, shorter time to BCR, and higher rates of metastases. Further studies are warranted to investigate the molecular underpinnings of IDC-P to better guide treatment strategies for this aggressive disease entity., Competing Interests: Disclosure RRM serves as consultant/advisor for Aveo, AstraZeneca, Bayer, BMS, Calithera, Caris, Dendreon, Exelixis, JNJ, Lilly, Myovant, Merck, Novartis, Pfizer, Sanofi, Sorrento Therapeutics, Telix, Tempus. Receives research funding from Bayer, Tempus, AstraZeneca, Oncternal Therapeutics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer., Methods: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC)., Results: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS., Conclusion: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)