Papers by Michael Hurwitz
JNCI Cancer Spectrum, May 2, 2023
Molecular Cancer, Dec 14, 2022
PLOS Genetics, Dec 13, 2012
PLOS Biology, Apr 28, 2009
Cancer Discovery, Jun 1, 2019
Journal of Clinical Oncology, Sep 10, 2021
Journal for ImmunoTherapy of Cancer, Mar 1, 2023
Regular and Young Investigator Award Abstracts, Nov 1, 2022
Journal for ImmunoTherapy of Cancer, Aug 1, 2023
Frontiers in Oncology
While great strides have been made in the treatment of advanced renal cell carcinoma (RCC) with t... more While great strides have been made in the treatment of advanced renal cell carcinoma (RCC) with the emergence of immune checkpoint inhibitors (ICIs) and VEGFR-targeting drugs, sizable proportions of patients still do not respond to upfront therapy and long-term responses only occur in a minority of patients. There is therefore a great need for the development of better predictors of response and an increased understanding of mechanisms of resistance to these therapies. Alternative immune checkpoints outside the PD-1/PD-L1 axis, such as LAG3, have been implicated as one mechanism of resistance to ICIs. These checkpoints thus represent attractive therapeutic targets, and indeed the LAG3 inhibitor relatlimab was recently approved for the treatment of metastatic melanoma in combination with anti-PD-1 therapy. LAG3 inhibitors are being evaluated for RCC as well. In this context, a better understanding of LAG3 expression patterns in RCC and how they relate to clinicopathologic features of...
Journal of Translational Medicine, Aug 16, 2022
Background: The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predict... more Background: The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predicted benefit to immune checkpoint inhibitor (ICI) therapy in triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). It generates both a continuous score and a binary result using a defined threshold that is conserved between breast and lung. Herein, we aimed to evaluate the IO Score's binary threshold in ICI-naïve TCGA bladder cancer patients (TCGA-BLCA) and assess its clinical utility in metastatic urothelial cancer (mUC) using the IMvigor210 clinical trial treated with the ICI, atezolizumab. Methods: We identified a list of tumor immune microenvironment (TIME) related genes expressed across the TCGA breast, lung squamous and lung adenocarcinoma cohorts (TCGA-BRCA, TCGA-LUSQ, and TCGA-LUAD, 939 genes total) and then examined the expression of these 939 genes in TCGA-BLCA, to identify patients as having high inflammatory gene expression. Using this as a test of classification, we assessed the previously established threshold of IO Score. We then evaluated the IO Score with this threshold in the IMvigor210 cohort for its association with overall survival (OS). Results: In TCGA-BLCA, IO Score positive patients had a strong concordance with high inflammatory gene expression (p < 0.0001). Given this concordance, we applied the IO Score to the ICI treated IMvigor210 patients. IO Score positive patients (40%) had a significant Cox proportional hazard ratio (HR) of 0.59 (95% CI 0.45-0.78 p < 0.001) for OS and improved median OS (15.6 versus 7.5 months) compared to IO Score negative patients. The IO Score remained significant in bivariate models combined with all other clinical factors and biomarkers, including PD-L1 protein expression and tumor mutational burden. Conclusion: The IMvigor210 results demonstrate the potential for the IO Score as a clinically useful biomarker in mUC. As this is the third tumor type assessed using the same algorithm and threshold, the IO Score may be a promising candidate as a tissue agnostic marker of ICI clinical benefit. The concordance between IO Score and inflammatory gene expression suggests that the classifier is capturing common features of the TIME across cancer types.
Journal of Clinical Oncology, 2016
439 Background: The male predilection of urothelial bladder cancer (UBC) as well as the expressio... more 439 Background: The male predilection of urothelial bladder cancer (UBC) as well as the expression of the androgen receptor in bladder tissue point to the role for androgens in UBC tumorigenesis. Animal studies demonstrate a potential role for androgen deprivation in diminishing UBC. More recently, two separate groups demonstrated decreased rates of both primary and recurrent UBC in prostate cancer patients previously receiving androgen deprivation therapy (ADT). Given the common use of radiation therapy (RT) in the treatment of localized prostate cancer, and previous data supporting the increased frequency of UBC in prostate cancer patients treated with RT, the interaction between ADT and RT in UBC remains an important consideration. Methods: Using the linked SEER-Medicare database, we investigated the interactions among ADT, RT and UBC by performing a retrospective cohort study of elderly (age 66-99) prostate cancer patients diagnosed between 1999-2011. Kaplan-Meier analysis and C...
Journal of Clinical Oncology, 2016
295 Background: The bone seeking calcium mimetic, Radium223 (Ra223), emits high energy alpha part... more 295 Background: The bone seeking calcium mimetic, Radium223 (Ra223), emits high energy alpha particle that cause irreparable double strand DNA breaks in osseous metastases. Ra223 improves survival in patients with bone-predominant metastatic castration resistant prostate cancer (mCRPC). The effect of Ra223 on the host immune system, and T cell immunity in particular, is unknown. Methods: Eligible patients include men with mCRPC, osseous metastases and a clinical indication for Ra223 were eligible. Blood samples were collected at the following time points: prior to the first, second, and fourth treatments (tx) and 4 weeks after the sixth dose. Peripheral blood mononuclear cells (PBMCs) were purified and stained with a cocktail of antibodies to surface and effector immune molecules. Some PBMCs were stimulated and stained for intracellular cytokines (IFN-g, TNF-a, IL-13, IL-17, and IL-21). Stained cells were analyzed by flow cytometry. Results: A total seven patients completed at least...
Journal of the National Comprehensive Cancer Network, 2019
The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratif... more The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.
Background The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predicte... more Background The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predicted benefit to immune checkpoint inhibitor (ICI) therapy in triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). It generates both a continuous score and a binary result using a defined threshold that is conserved between breast and lung. Herein, we aimed to evaluate the IO Score’s binary threshold in ICI-naïve TCGA bladder cancer patients (TCGA-BLCA) and assess its clinical utility in metastatic urothelial cancer (mUC) using the IMvigor 210 clinical trial treated with the ICI, atezolizumab. Methods We identified a list of tumor immune microenvironment (TIME) related genes expressed across the TCGA breast, lung squamous and lung adenocarcinoma cohorts (TCGA-BRCA, TCGA-LUSQ, and TCGA-LUAD, 939 genes total) and then examined the expression of these 939 genes in TCGA-BLCA, to identify patients as having high inflammatory gene expression. Using this as a test of classif...
Journal of Clinical Oncology
288 Background: Nivolumab (nivo) is FDA approved for patients (pts) with VEGFR TKI-resistant RCC ... more 288 Background: Nivolumab (nivo) is FDA approved for patients (pts) with VEGFR TKI-resistant RCC and the nivo + ipilimumab (nivo/ipi) combination is FDA approved for treatment naïve pts with IMDC intermediate and poor risk renal cell carcinoma (RCC). Little information was available on the efficacy and toxicity of nivo monotherapy in treatment naïve RCC or the efficacy of nivo/ipi salvage in pts with tumors resistant to initial nivo monotherapy. Methods: Eligible pts with treatment naïve RCC received nivo 240mg IV q2 wk x 6 doses followed by 360mg IV q3 wk x 4 doses followed by 480 mg q4 wk until progressive disease (PD), toxicity, or completion of 96 wks of treatment (Part A). Pts with PD prior to, or stable disease (SD) at 48 wks (pSD) were potentially eligible to receive salvage nivo (3mg/kg)/ipi (1 mg/kg) q3 wk x 4 doses followed by q4 wk nivo maintenance for up to 48 wks (Part B). All pts were required to submit tissue from a metastatic lesion obtained within 12 months (mos) pr...
Journal of Clinical Oncology, 2021
PURPOSE Therapies that produce deep and durable responses in patients with metastatic melanoma ar... more PURPOSE Therapies that produce deep and durable responses in patients with metastatic melanoma are needed. This phase II cohort from the international, single-arm PIVOT-02 study evaluated the CD122-preferential interleukin-2 pathway agonist bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) in first-line metastatic melanoma. METHODS A total of 41 previously untreated patients with stage III/IV melanoma received BEMPEG 0.006 mg/kg plus NIVO 360 mg once every 3 weeks for ≤ 2 years; 38 were efficacy-evaluable (≥ 1 postbaseline scan). Primary end points were safety and objective response rate (blinded independent central review); other end points included progression-free survival, overall survival (OS), and exploratory biomarkers. RESULTS At 29.0 months' median follow-up, the objective response rate was 52.6% (20 of 38 patients), and the complete response rate was 34.2% (13 of 38 patients). Median change in size of target lesions from baseline was −78.5% (response-evaluable populatio...
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Papers by Michael Hurwitz