ESMO 2018 - Results from #20

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ESMO 2018: KEYNOTE-427 Cohort A: Pembrolizumab Monotherapy as First-line Therapy in advanced clear cell Renal Cell Carcinoma (ccRCC)

Munich, Germany (UroToday.com) Several studies are underway studying PD-1/PD-L1 in combination with VEGFR or TKI blockade. Current phase III trials include pembrolizumab + axitinib, pembrolizumab + lenvatinib, avelumab + axitinib, and nivolumab + cabozantinib. Results from IMmotion 151 showed that combination therapy with atezolizumab and bevacizumab is efficacious in first-line therapy of mRCC with respect to improving progression-free survival¹.

ESMO 2018: Activity of Cabozantinib After PD-1/PD-L1 Immune Checkpoint Blockade In Metastatic Clear Cell Renal Cell Carcinoma

Munich, Germany ( UroToday.com) Cabozantinib is an oral small molecule multikinase inhibitor which targets c-MET, VEGFR2, AXL, and RET, and a standard of care therapy for both first line and second line therapy of metastatic RCC. In a phase II multicenter study which randomized patients to front-line sunitinib or cabozantinib for mRCC, cabozantinib increased median progression free survival (8.2 months vs 5.6 months) with a 34% reduction in rate of death or progression (HR 0.66, 95%CI 0.46-0.95)¹.

ESMO 2018: COSMIC-021, Phase Ib Study of Cabozantinib in Combination with Atezolizumab and Potent Natural Killer, Myeloid Blood Cell Remodeling by Cabozantinib

Munich, Germany ( UroToday.com) Cabozantinib is a multikinase inhibitor of MET, VEGFR, AXL and RET¹. In the sphere of metastatic renal cell carcinoma, cabozantinib is currently being used in both first line and second line therapy, based on CABOSUN for first line and METEOR for second line^2,3. In addition to being a tyrosine kinase inhibitor, there is some evidence that cabozantinib may alter the tumor immune microenvironment, altering regulatory T cells (T_regs) as well as myeloid-derived suppressor cells (MDSC)⁴.

ESMO 2018: Clinical Experience of 100 Consecutive Patients Treated with Lu-177-labeled PSMA-I&T Radioligand Therapy for mCRPC

Munich, Germany (UroToday.com) Prostate-specific membrane antigen (PSMA) is a unique protein, coded on the short arm of chromosome 11, which has enzymatic activity acting as a glutamate-preferring carboxypeptidase¹. PSA (prostate specific antigen) and PSMA differ in many ways, but one of the most unique features of PSMA is that PSMA expression appears to be inversely related to androgen levels and in preclinical models, PSMA activity increased as cell lines became androgen independent².

ESMO 2018: ABACUS, A phase II Study Investigating the Safety and Efficacy of Neoadjuvant Atezolizumab in Muscle Invasive Bladder Cancer

Munich, Germany ( UroToday.com) There is a high metastatic relapse rate for patients with muscle-invasive bladder cancer after cystectomy – neoadjuvant chemotherapy can decrease that risk. The standard of care neoadjuvant therapy for muscle-invasive bladder cancer typically involves a cisplatin-based regimen, the most common being MVAC (methotrexate, vinblastine, doxorubicin, cisplatin), GC (gemcitabine and cisplatin), or CMV (cisplatin, vinblastine, and methotrexate). Compared with cystectomy alone, neoadjuvant chemotherapy can improve overall survival and decrease the risk of recurrence^1,2

ESMO 2018: What is New in Metastatic Castration Resistant Prostate Cancer?

Munich, Germany (UroToday.com) Updates in the last 14 years in the growing field of metastatic castrate-resistant prostate cancer (mCRPC) were discussed in a detailed manner, in a talk given by Ronald De Wit, MD

ESMO 2018: The Prognostic Value of the Proportion and Subtype Patterns of Intraductal Carcinoma with De Novo Metastatic Prostate Cancer: A Propensity Score Matching Study

Munich, Germany ( UroToday.com) It is well established that the presence of intraductal carcinoma (IDC) of the prostate is an adverse prognostic factor, with respect to PSA failure, progression-free survival, and cancer-specific survival in patients with localized prostate cancer¹. In a retrospective study of 206 patients who underwent radical prostatectomy in Japan, of the patients who had a clinical relapse, 79.5% had IDC in their pathology report. 20 patients had died of prostate cancer in follow up, of which 17 patients (85%) had IDC.

ESMO 2018: STAMPEDE - Effects of Abiraterone Acetate plus Prednisone/Prednisolone in High and Low Risk Metastatic Hormone Sensitive Prostate Cancer

Munich, Germany (UroToday.com) Dr. Hoyle, on behalf of the STAMPEDE clinical trial group, presented the data on the effects of abiraterone acetate (AA) plus prednisone/prednisolone (P) [AAP] in high and low risk metastatic hormone sensitive prostate cancer (mHSPC). This is a very important presentation with significant clinical implications.

ESMO 2018: Avelumab + Axitinib vs Sunitinib for the Management of Advanced Renal Cell Carcinoma - JAVELIN Renal 101

Munich, Germany (UroToday.com) Dr. Motzer, on behalf of the JAVELIN clinical trial group, presents the results of the first study to combine a targeted therapy and immune checkpoint inhibitor for the management of advanced renal cell carcinoma (aRCC).

ESMO 2018: Statin Use and Outcome in Metastatic Castration-Resistant Prostate Cancer Patients Treated in the TROPIC Trial

Munich, Germany (UroToday.com) Statins, also known as HMG-CoA reductase inhibitors, are a class of low molecular weight drugs which have been shown in preclinical models to demonstrate antitumor activity through apoptosis and cell growth arrest in three prostate cancer cell lines1. In a large prospective cohort study of 34,989 male health professionals in the United States, the age-standardized incidence rates of advanced prostate cancer were 38 per 100,000 person-years in current statin users and 89 per 100,000 person-years, with a relative risk of advanced disease of 0.51 (95% confidence interval [CI] = 0.30 to 0.86) for statin users2. Similar findings have been reported utilizing a database of patients from the Portland Oregon Veteran Affairs Medical Center where statin use was also associated with a reduction in prostate cancer risk (odds ratio = 0.38, 95% confidence interval: 0.21, 0.69)3. These studies suggest that long-term statin use may be associated with a reduced risk of prostate cancer.

ESMO 2018: Survival Results from STAMPEDE, Local Radiotherapy Improves Survival in Metastatic Prostate Cancer with Low Disease Burden

Munich, Germany (UroToday.com) Chris Parker, MD on behalf of the STAMPEDE clinical trials group, presented this first report of the role of radiotherapy to the primary tumor for men with newly diagnosed metastatic prostate cancer (mPCa). This is the latest arm to report from the novel STAMPEDE clinical trial, which is an ongoing clinical trial that can add arms as it progresses – having already recruited over 10,000 men.

ESMO 2018: Oligometastatic Disease - The Critical Need of a Multidisciplinary Approach for the Treatment of Prostate Cancer

Munich, Germany (UroToday.com) The oligometastatic disease has a variety of definitions, with some supporting the definition of up to five extra-pelvic metastatic lesions. The oligometastatic disease state is presumed to be an intermediate stage between localized disease and widespread metastases. Nowadays, there are improved diagnostic methods that enable us to increase the diagnostic accuracy of oligometastatic disease. There have been several retrospective studies analyzing the impact of various interventions for this disease state, including local or metastases directed radiotherapy and radical prostatectomy.

ESMO 2018: Effects of Abiraterone Acetate plus Prednisone/Prednisolone in High and Low Risk Metastatic Hormone Sensitive Prostate Cancer

Munich, Germany (UroToday.com) Several trials have now examined the use of abiraterone in metastatic castration sensitive prostate cancer (mCSPC). LATITUDE found that abiraterone not only improved time until subsequent therapy and PSA progression but also improved overall survival for patients with mCSPC¹.However, in LATITUDE, patients were required to have “high risk” disease, defined as two of the following risk factors: a Gleason score of 8 or greater, three bone lesions or greater, or the presence of measurable visceral metastasis.

ESMO 2018: Update on Diagnosis and Treatment of Localized Prostate Cancer

Munich, Germany (UroToday.com) Dr. Mark Emberton, gave a discussion on the diagnosis and treatment of localized prostate cancer. According to Dr. Emberton, a renowned urologist, based in London, UK, the most important event in localized prostate cancer in the last decade, in terms of early disease risk stratification, is the introduction of imaging into the diagnostic pathway to confer location. The incorporation of imaging in the diagnostic process has provided us with a vast amount of information that we did not have before. This includes location, volume, multiplicity, and probability.

ESMO 2018: Radiotherapy to the Primary Tumour for Men with Newly-Diagnosed Metastatic Prostate Cancer: Survival Results from STAMPEDE

Munich, Germany (UroToday.com) Radiation to the primary tumor in the setting of metastatic castration sensitive prostate cancer (mCSPC) is controversial. A large retrospective population-based study (SEER) found that five-year overall survival might be improved if local therapy is administered (radical prostatectomy or brachytherapy) compared with no local surgery at all.¹ Another retrospective study using a different American database (NCDB) saw improvement in overall survival when mCSPC were treated with prostate radiotherapy (RT).²

ESMO 2018: JAVELIN Renal 101: A Randomized, Phase 3 Study of Avelumab + Axitinib vs Sunitinib as First-Line Treatment of Advanced Renal Cell Carcinoma

Munich, Germany (UroToday.com) Frontline therapy for advanced renal cell carcinoma (RCC) has rapidly evolved over the past decade, with the addition of several new vascular endothelial growth factor (VEGF)-directed agents as well as immune checkpoint inhibitors. For patients with intermediate or high-risk disease, cabozantinib and combination ipilimumab+nivolumab have emerged as preferred frontline options based on data from CABOSUN and Checkmate 214^1,2.

Local Radiotherapy Improves Survival in Metastatic Prostate Cancer with Low Disease Burden

San Francisco, CA USA (UroToday.com) -- Radiotherapy to the prostate improves overall survival in men newly diagnosed with metastatic prostate cancer who have a low metastatic disease burden but not in those with higher burden of disease, according to results from a pre-planned analysis of a large comparison study reported at ESMO 2018¹.

Avelumab Plus Axitinib Significantly Improve Progression-Free Survival in Untreated Renal Cell Carcinoma

San Francisco, CA USA (UroToday.com) -- A combination of the immune checkpoint blocker, avelumab, plus the tyrosine kinase inhibitor (TKI), axitinib, significantly improves progression-free survival (PFS) in previously untreated patients with advanced renal cell carcinoma (RCC) in a phase 3 study, according to results presented at ESMO 2018 Congress.

ESMO 2018: Efficacy and Safety Results of GETUG, Axitinib in Metastatic Papillary Renal Cancer

Munich, Germany (UroToday.com) Papillary renal cell carcinoma (pRCC) is a rare form of RCC, which represents 15-20% of renal epithelial tumors¹. There is limited data on the best sequence of therapies for papillary RCCs. The largest randomized trial for pRCC was the ASPEN trial, which randomized 108 patients to either sunitinib or everolimus². In this study, patients treated with sunitinib had a longer median progression-free survival with sunitinib than everolimus (8.1 vs 5.5 months).

ESMO 2018: Tobacco Control: Saving Lives and Driving Development

Munich, Germany (UroToday.com) This talk in the advocacy session was by Gilberto Morgan, an American transplant to Sweden, who has a special interest in tobacco control.

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