ASCO 2018: Survival Outcomes from a Cumulative Analysis from Worldwide Observational Studies on Sequential use of New Agents in mCRPC

Chicago, IL (UroToday.com) In the past decade, it has been demonstrated that cabazitaxel1, abiraterone acetate2, and enzalutamide3 improved overall survival (OS) among men with CRPC who progress after docetaxel chemotherapy. As such, this has increased the number of available second-line therapeutic options, but at the same time, the availability of these new agents has led to the possibility of using them sequentially.  Several small retrospective reports described their activity when sequentially used as second- and third-line after docetaxel failure, which suggests that cabazitaxel-based sequences led to a better OS than sequences based on new hormonal therapies only. 

ASCO 2018: Analysis of Abiraterone Acetate + Prednisone in Patients with Newly Diagnosed High-Risk Metastatic Castration-Naïve Prostate Cancer - Phase 3 LATITUDE Trial

Chicago, IL (UroToday.com) At ASCO 2017 annual meeting, Dr. Fizazi and colleagues presented the first analyses of the phase III LATITUDE study [1]. LATITUDE set to evaluate the addition of abiraterone acetate (AA) + prednisone to ADT on clinical benefit in men with newly diagnosed, high-risk, metastatic hormone-naïve prostate cancer (n=1,199). The co-primary endpoints were OS and radiographic progression-free survival (rPFS). Secondary endpoints included time to: pain progression, PSA progression, next symptomatic skeletal event, chemotherapy, and subsequent prostate cancer therapy.

ASCO 2018: Alterations in Key Clear Cell Renal Cell Carcinoma Genes to Refine Patient Prognosis

Chicago, IL (UroToday.com) Currently, the IMDC classification, based on clinical factors, helps guide clinicians on prognosis in patients with metastatic RCC (mRCC). However, genetics can play an important role in clinical outcomes and treatment response. Certain genomic alterations have a well defined association with developing RCC, including (but not limited to): VHL, PBRM1, BAP1, SETD2, TP53 and KDM5C. Indeed, they are often found mutated on genomic analysis of mRCC patients. Yet, the prognostic value of these mutations above and beyond the IMDC classification is not clearly known.

ASCO 2018: Phase II Trial of Rucaparib in Patients with Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations

Chicago, IL (UroToday.com) PARP-inhibitors are a class of agents that have significant clinical activity in patients with DNA-repair mutations. Specifically, they are a class of agents that group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). PARP1 is a protein that is important for repairing single-strand break in the DNA - if such damage persist unrepaired until DNA is replicated, then the replication itself can cause double strand breaks to form. Drugs that inhibit PARP1 result in multiple double strand breaks to form in this way, and in tumors with BRCA1, BRCA2, PALB2, or other DNA-repair mutations, these double strand breaks cannot be efficiently repaired, leading to the death of the cells. 

ASCO 2018:  Apache: Open Label, Randomized, Phase 2 Study of Durvalumab, Alone or in Combination with Tremelimumab, in Patients with Advanced Germ Cell Tumors: Results at the End of First Stage

Chicago, IL (UroToday.com) Immune checkpoint inhibitors (ICIs) have had great success in multiple malignancies, including lung cancer, melanoma and bladder cancer. Within the GU field, it has primarily been limited to bladder cancer and RCC, due to the higher mutational burden and subsequent higher antigen load. However, there has been little evaluation to date in patients with testicular cancer. 

ASCO 2018: Characterizing Tumor Immune Microenvironment and Outcomes for 409 Patients Treated On COMPARZ: Distinct Clusters Emphasize Immune Infiltration Vs. Angiogenesis

Chicago, IL (UroToday.com) Our knowledge of cancer biology has continued to grow exponentially in the era of big data. Amongst the knowledge gained is that cancer cells do not grow in a void – rather they are significantly impacted by the cells around them; stromal tissue, tissue infiltrates, etc. The collection of immune cells in the vicinity of the tumor, called tumor immune microenvironent (TME) has been demonstrated to be associated with tumor natural history and response to therapy. Previously examined on a histologic level, recent advances in next-generation sequencing (NGS) have begun to explore this on a larger scale.

ASCO 2018: VinCaP: A Phase II Trial of Vinflunine Chemotherapy in Locally-Advanced and Metastatic Carcinoma of the Penis (CRUK/12/021)

Chicago, IL (UroToday.com) Metastatic penile cancer continues to carry significant morbidity and mortality despite systemic therapy. Current management unfortunately still carries a 10-20% 5-year mortality risk for patients with metastatic disease. Advances in systemic therapy are drastically needed.
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