Showing papers by "Thomas W. Flaig published in 2019"
National Institutes of Health1, Aarhus University Hospital2, Huntsman Cancer Institute3, The Royal Marsden NHS Foundation Trust4, Monash Medical Centre5, Herlev Hospital6, University of Colorado Boulder7, Hebron University8, Université de Montréal9, La Roche College10, Aalborg University11, Memorial Sloan Kettering Cancer Center12
TL;DR: Whereas PROSTVAC was safe and well tolerated, it had no effect on OS or AWE in metastatic castration-resistant prostate cancer, and the trial was stopped early.
Abstract: PURPOSEPROSTVAC, a viral vector–based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate cancer in a phase II study. This...
155 citations
Case Western Reserve University1, Memorial Sloan Kettering Cancer Center2, Stanford University3, Yale Cancer Center4, University of North Carolina at Chapel Hill5, University of Miami6, Emory University7, University of Minnesota8, Seattle Genetics9, Astellas Pharma10, University of Colorado Boulder11
TL;DR: In 1L cis-ineligible pts with la/mUC, EV + pembrolizumab demonstrates encouraging efficacy with a tolerable and manageable safety profile, and combination therapy may provide additional benefit.
43 citations
TL;DR: The 2019 version of the NCCN Guidelines has integrated changes to tumor staging that reflect an updated understanding of the natural history of the disease and will affect how patients are treated.
Abstract: The treatment landscape of bladder cancer has changed rapidly over the past several years. The 2019 version of the NCCN Guidelines has integrated changes to tumor staging that reflect an updated understanding of the natural history of the disease and will affect how patients are treated. Further, 5 PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are approved for the treatment of bladder cancer. The FDA has limited use of ICIs as monotherapy in the first-line treatment of metastatic and advanced disease for patients who are platinum-ineligible or are cisplatin-ineligible with high PD-L1 expression and are candidates for ICIs. Ongoing predictive biomarker development and validation are needed in bladder cancer; the development of better biomarkers will be key in patient selections for therapy going forward.
38 citations
TL;DR: This data indicates that angiogenesis plays a role in UC growth and cisplatin treatment with gemcitabine-C is a standard therapy for metastatic urothelial carcinoma.
Abstract: 4503Background: The combination of gemcitabine (G) and cisplatin (C) is a standard therapy for metastatic urothelial carcinoma (mUC). Based on data that angiogenesis plays a role in UC growth and p...
35 citations
TL;DR: Efficient targeting of bladder cancer cells with UCNP-AuNR nanoclusters is demonstrated, for the first time, and highly selective optoporation-assisted chemotherapy was accomplished using a dosage of chemotherapy agent significantly lower than any previous reports, within a clinically relevant incubation time window.
31 citations
University of Colorado Boulder1, Fred Hutchinson Cancer Research Center2, University of Southern California3, University of Michigan4, Baylor College of Medicine5, Anschutz Medical Campus6, Johns Hopkins University7, Cedars-Sinai Medical Center8, University of North Carolina at Chapel Hill9, Cleveland Clinic10, Colorado State University11
TL;DR: Both dose-dense Methotrexate-Vinblastine-Adriamycin/doxorubicin-CISplatin and Gemcitabine-Cisplatin are accepted neoadjuvant regimens for muscle-invasive bladder cancellation.
Abstract: 4506Background: Both dose-dense Methotrexate-Vinblastine-Adriamycin/doxorubicin-Cisplatin (ddMVAC) and Gemcitabine-Cisplatin (GC) are accepted neoadjuvant regimens for muscle-invasive bladder cance...
27 citations
TL;DR: “Platinum-ineligible” mUC is a new and undefined category with a substantial definition variability among investigators and results from consensus definition are proposed for standardization of this mUC category.
Abstract: 451Background: Patients (pts) with mUC who are ineligible to receive cisplatin have limited treatment options. Pembrolizumab and atezolizumab were approved as 1st-line therapy in these pts, but the...
22 citations
Memorial Sloan Kettering Cancer Center1, Princess Margaret Cancer Centre2, University of Michigan3, Tom Baker Cancer Centre4, University of Colorado Boulder5, University of Kansas6, University of Wisconsin-Madison7, Fox Chase Cancer Center8, Cross Cancer Institute9, Wayne State University10, University of Miami11, University of Southern California12, Stanford University13, University of North Carolina at Chapel Hill14, Astellas Pharma15, Seattle Genetics16, Yale Cancer Center17
TL;DR: Single-agent EV was generally well tolerated and provided encouraging response and survival data in a population with an unmet medical need including pts with LM, which is associated with poor prognosis.
Abstract: 377Background: Enfortumab vedotin (EV) is an antibodydrug conjugate that delivers MMAE, a microtubule disrupting agent, to tumors expressing Nectin-4, a protein found on most urothelial cancers. P...
20 citations
TL;DR: The MTD was determined to be pembro 200 mg Q3W and cabo 60 QD and the clinical benefit rate was 87.5%.
Abstract: 600Background: PD-L1- and VEGF-targeted therapies have improved survival for mRCC pts and mechanisms of synergy have been reported. We conducted a phase I/II study to evaluate the safety and effica...
11 citations
TL;DR: PD-(L)1-targeted immune checkpoint inhibitors (CPIs), such as pembrolizumab (P), are approved for patients with locally advanced or metastatic urothelial cancer (la/mUC) wh...
Abstract: TPS4593Background: PD-(L)1-targeted immune checkpoint inhibitors (CPIs), such as pembrolizumab (P), are approved for patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) wh...
8 citations
Wayne State University1, University of Maryland, Baltimore2, University of Wisconsin-Madison3, University of California, Davis4, Ohio State University5, University of Colorado Denver6, University of Texas MD Anderson Cancer Center7, Michigan State University8, Case Western Reserve University9, National Institutes of Health10
TL;DR: Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docentaxel+prednisone, and added toxicity, and the data do not support pursuing the combination further in patients with mCRPC.
Abstract: Lessons learned The negative results are consistent with the negative results of large phase III trials in which docetaxel plus antiangiogenic agents were used in patients with metastatic castrate-resistant prostate cancer (mCRPC).The negative data underscore that, despite a sound biological rationale and supportive early-phase clinical results, adding antiangiogenic agents to docetaxel for mCRPC is a great challenge. Background Inhibition of vascular endothelial growth factor (VEGF) signaling abrogates tumor-induced angiogenesis to constrain tumor growth, and can be exploited therapeutically by using cediranib, an oral tyrosine kinase inhibitor of VEGF receptor signaling. Our preliminary phase I trial data showed that adding cediranib to docetaxel plus prednisone (DP) was safe and feasible, with early evidence for efficacy in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods This multicenter phase II trial assessed whether adding cediranib to DP improves efficacy of DP in patients with mCRPC. Chemotherapy-naive patients with mCRPC were randomly assigned to receive either docetaxel (75 mg/m2 intravenously every 3 weeks) with prednisone (5 mg twice daily) plus cediranib (30 mg once daily; the DP+C arm) or DP only (the DP arm). The primary endpoint was to compare 6-month progression-free survival (PFS) rate between the two arms. Secondary endpoints included 6-month overall survival (OS), objective tumor and prostate-specific antigen (PSA) response rates, biomarkers, and adverse events. Results The 6-month PFS rate in a total of 58 patients was only numerically higher in the DP+C arm (61%) compared with the DP arm (57%). Similarly, the 6-month OS rate, objective tumor and PSA response rates, and biomarkers were not significantly different between the two arms. Increased baseline levels of interleukin 6 (IL-6), however, were significantly associated with increased risk of progression. Neutropenia was the only grade 4 toxicity (38% in the DP+C arm vs. 18% in the DP arm). Conclusion Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docetaxel + prednisone, and added toxicity. Our data do not support pursuing the combination further in patients with mCRPC.
TL;DR: The Phase 3 ARCHES trial evaluated the efficacy and safety of ENZ + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT in 1150 men with mHSPC and reported positive results.
Abstract: 5044Background: The Phase 3 ARCHES trial (NCT02677896) evaluated the efficacy and safety of ENZ + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT in 1150 men with mHSPC. Here we report pa...