ESMO 2018

ESMO 2018: Preliminary results from TRITON2: A Phase II Study of Rucaparib in Patients with Metastatic Castration-Resistant Prostate Cancer Associated with Homologous Recombination Repair Gene Alterations

Munich, Germany (UroToday.com) Patients with inherited mutations in DNA repair genes such as BRCA2 have an association with increased risk of lethal prostate cancer. In a multicenter study incorporating 7 databases of patients with metastatic prostate cancer, 11.8% percent of patients were found to have germline DNA repair genes.¹ In another cohort of patients, 22.7% of patients had alterations in DNA repair and DNA recombination genes^²

2018 ESMO Immuno-Oncology Award Goes to Cornelis Melief

San Francisco, CA USA (UroToday.com) -- The European Society for Medical Oncology (ESMO) has selected Prof. Cornelis Melief to receive the 2018 ESMO Immuno-Oncology Award in recognition of his life’s work in studying the interactions of the immune system with cancer. The distinction will be officially presented to him at the opening keynote and award lecture of this year’s ESMO Immuno-Oncology Congress in Geneva, Switzerland (13-16 December).^¹

ESMO 2018: The Best of Munich 2018 Congress Genitourinary Tumors, Prostate

Munich, Germany (UroToday.com) Silke Gillessen, MD summarized the highlights of prostate cancer studies presented this year in ESMO. A total of four important prostate cancer studies in three different prostate cancer settings were presented in this session, deemed to be very important by Dr. Gillessen.

ESMO 2018: Can Biology Help Guide Treatment Decisions in Renal Cancer?

Munich, Germany (UroToday.com) When assessing the completed combination trials in metastatic renal cell carcinoma (mRCC), most studies have met their anticipated endpoints. When all various treatments have been shown to be successful, this makes deciding which treatment will be right for which patients difficult.

ESMO 2018: The Best of Munich 2018 Congress - Genitourinary Tumors, Non-Prostate

Munich, Germany (UroToday.com) Dr. Bono discussed some of the highlights in renal and bladder cancer that were presented this year in ESMO 2018, in Munich. He first discussed some of the interesting studies in renal cancer. In the last ten years, there have been ten new agents that have been made available for the treatment of metastatic renal cell carcinoma (mRCC). The median survival of these new agents is approximately 28-30 months.

ESMO 2018: Challenging Established Frontline Therapies in Renal Cancer

Munich, Germany (UroToday.com) Dr. Laurence Albiges gave a talk on the challenges faced by established frontline therapies in renal cancer. In the ESMO meeting in 2017, the Checkmate 214 trial was presented, which compared sunitinib to Nivolumab + ipilimumab in the treatment of metastatic renal cell carcinoma (mRCC) patients. This trial demonstrated a benefit in favor of the nivolumab + ipilimumab combination in poor and intermediate risk mRCC patients, with median overall survival (OS) that was not reached compared to 26 months in the sunitinib group, p<0.0001. The complete response rate (CR) was 9% vs. 1% in favor of the combination treatment.

ESMO 2018: WHO-ESMO Workforce Survey: How Can your Country Assure Enough Oncologists for the Future?

Munich, Germany (UroToday.com) When analyzing what kind of health workforce is required in any specific environment. It is important to answer some raised relevant questions:

How many providers are needed?
What type of providers are needed?
How to organize and distribute providers?
How to ensure providers are adequately trained to provide high-quality care.

ESMO 2018: Where Does the World Stand on Global Cancer Control?

Munich, Germany (UroToday.com) Cancer causes 9.6 million deaths per year worldwide (1 in 6 global deaths). This is a higher number than that caused by AIDS, Malaria, and Tuberculosis, combined! Unfortunately, being diagnosed with cancer in a low-income country results in chances of survival of less than 30%. The cancer burden is expected to rise significantly from 18.1 million cases per year in 2018 to 29.9 million cases per year in 2040.

ESMO 2018: Invited Discussant - Genomics of Prostate Cancer for Precision Medicine Based on DNA Repair Defects

Munich, Germany (UroToday.com) Joaquin Mateo, MD gave a summary presentation on three major posters presented ESMO 2018. These posters included: 1. 793PD - Preliminary results from TRITON2: a phase 2 study of rucaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination repair (HRR) gene alterations – Wassim Abida, New York, US. 2. 794PD - Prospective comprehensive genomic profiling (CGP) of 3,476 primary and metastatic site prostate tumors – Siraj Ali, Cambridge, US. 3. 795PD - Genomic profiling of circulating tumor DNA (ctDNA) and tumor tissue for the evaluation of rucaparib in metastatic castration-resistant prostate cancer (mCRPC) – Simon Chowdhury, London, UK

ESMO 2018: Invited Discussant - Detection of Circulating Tumor DNA in mHSPC and LATITUDE Study

Munich, Germany (UroToday.com) Joe O’Sullivan, MD, gave a discussion summarizing two important posters presented at ESMO 2018 in Munich. These included:

796PD - Detection of circulating tumor DNA in de novo metastatic castrate-sensitive prostate cancer – Werner Strauss et al.
797PD - LATITUDE study: PSA response characteristics and correlation with overall survival (OS) and radiological progression-free survival in patients with metastatic hormone-sensitive prostate cancer receiving ADT+abiraterone acetate and prednisone or placebo – Nobiaki Matsubara et al.

ESMO 2018: Invited Discussant - mCRPC with High Tumor Mutational Burden and a Phase I Dose-Escalation Study of 177Lu-PSMA-617 for mCRPC

Munich, Germany (UroToday.com) Aristotelis Bamias, MD discussed the following two studies:

798PD - In-depth assessment of metastatic prostate cancer with the high tumor mutational burden – Niven Mehra et al.
799PD - Phase I dose-escalation study of fractionated dose 177Lu-PSMA-617 for progressive metastatic castration-resistant prostate cancer (mCRPC) – Scott Tagawa et al.

ESMO 2018: How Many Patients Can One Oncologist Care For?

Munich, Germany (UroToday.com) According to the World Health Organization (WHO) the definition of the health workforce, is: “all the people engaged in actions whose primary intent is to enhance health.” These could be clinical (physicians, nurses, physician assistants, and others), and non-clinical personnel (Administration and support staff).

ESMO 2018: Improving Treatment Outcome by Manipulating the Immune System

Munich, Germany (UroToday.com) Dr. Winald R. Gerritsen gave an overview of the role of immunotherapy in prostate cancer.

There have been several vaccinations that have been specifically developed for prostate cancer. These include:

Sipuleucel T – demonstrating a median four months overall survival advantage vs. placebo, with an immune response in 70% of patients
G-VAX – Two phase 3 studies comparing it vs. docetaxel had failed

ESMO 2018: Randomized Trial of ADT + Enzalutamide Versus ADT + Bicalutamide in Metastatic Hormone Sensitive Prostate Cancer

Munich, Germany (UroToday.com) Enzalutamide is an androgen signaling inhibitor which prevents androgen receptor nuclear translocation and DNA binding, therefore leading to cellular apoptosis. Enzalutamide has been largely studied in the metastatic castration-resistant population, demonstrating an overall survival benefit for patients before and after chemotherapy^1,2. In an open-label, single arm, phase II study, enzalutamide was also found to be well tolerated in patients with castration-sensitive prostate cancer, with 92.5% of patients achieving at 80% PSA decline or greater by week 25 of therapy³. However, it is unknown if enzalutamide is more effective than bicalutamide in combination with standard ADT for patients with metastatic castration sensitive prostate cancer.

ESMO 2018: Cabazitaxel Treatment in mCRPC Clinical Trials Compared to Usual Care In CAPRI: An Observational Study In The Netherlands

Munich, Germany (UroToday.com) TROPIC was a randomized open label phase III clinical trial which compared the efficacy of cabazitaxel to mitoxantrone in patients with mCRPC who had progressed on docetaxel¹. 755 men were randomized and included in the intention to treat analysis. At the time of final analysis, cabazitaxel improved overall survival (15.1 vs 12.7 months, HR 0.7, p<0.0001) as well as median progression free survival.

ESMO 2018: Improving Outcome by Optimizing Combination and Sequencing of Treatments

Munich, Germany (UroToday.com) There are currently four approved systemic therapies by biologic domain in advanced prostate cancer:

Novel androgen signaling inhibition – abiraterone and enzalutamide
Chemotherapy – docetaxel, cabazitaxel
Immunotherapy – Sipuleucel T
Bone-targeting agents – Radium 223

ESMO 2018: Improving Treatment Outcome by Dissecting Heterogeneity

Munich, Germany (UroToday.com) Dr. Johann De Bono gave a presentation on the heterogeneity of prostate cancer and the possible strategies to improve treatment, focusing the novel available biomarkers.

In recent years, there have been major advances with increasing complex landscape. Multiple systemic agents have been shown to increase survival. Castrate resistant prostate cancer (CRPC) remains nuclear steroid hormone receptor-driven.

ESMO 2018: Results of PROSPER by Age and Region - A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Enzalutamide in Men with nmCRPC

Munich, Germany (UroToday.com) During GU ASCO 2018, Dr. Hussain presented the results of PROSPER (NCT02003924), a phase III randomized, double-blind, placebo-controlled study of enzalutamide in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC)¹. Prior to this study, there were no approved therapies for men with M0 CRPC, and in particular men with high-risk disease with PSA doubling times less than 10 months. In this study, the authors hypothesized that enzalutamide would be able to delay the development of metastases in men with M0 CRPC in this high-risk population and thus the primary endpoint was metastases-free survival, defined as the time from randomization to radiographic progression or death within 112 days of treatment discontinuation.

ESMO 2018: PRINCIPAL Study - Real-World Effectiveness of Pazopanib in Patients with Intermediate Prognostic Risk Advanced Renal Cell Carcinoma

Munich, Germany (UroToday.com) Pazopanib is a multikinase inhibitor which limits tumor growth via inhibition of angiogenesis by inhibiting VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, FGFR-1, FGFR-3, cKIT, interleukin-2 receptor inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms)¹. In a phase III trial, pazopanib was shown to be superior to placebo in both treatment naïve and cytokine-pretreated patients with advanced or metastatic RCC².

ESMO 2018: Safety and Tolerability of Atezolizumab plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma: IMmotion 150 and IMmotion 151

Munich, Germany (UroToday.com) IMmotion 150 (Phase II) compared the efficacy of atezolizumab (atezo) plus bevacizumab (bev) with atezolizumab alone and sunitinib alone and then allowed for crossover in the latter 2 arms to atezolizumab plus bevacizumab.¹ IMmotion 151 (Phase III) compared the efficacy of atezolizumab plus bevacizumab vs sunitinib for first-line therapy of metastatic renal cell carcinoma².

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