ASCO GU 2019 Penile, Urethral, Testicular, and Adrenal Cancers

ASCO GU 2019 Penile, Urethral, Testicular, and Adrenal Cancers

ASCO GU 2019: Fierce-21: Phase II Study of Vofatamab, a Selective Inhibitor of FGFR3, as Salvage Therapy in Metastatic Urothelial Carcinoma

San Francisco, CA (UroToday.com) Somatic activating mutations of FGFR3 were first described over a decade ago in patients with bladder and cervical cancer.1 According to 9 prior bladder cancer cohorts on CBIO portal, FGFR3 is altered anywhere from 7% to 20% of all cases (Figure 1). Gene fusions occur in up to 2% of patients and FGFR3 amplification occurs in up to 3% of cases. In non-muscle invasive bladder cancer, FGFR3 is thought to identify patients who have a lower risk of recurrence.2 In patients with Metastatic Urothelial Cancer (mUC), FGFR is a potential target of therapy and several FGFR inhibitors are now in early phase clinical trials.

ASCO GU 2019: Health-Related Quality of Life Reporting in Phase III Randomized Controlled Trials of Metastatic Prostate Adenocarcinoma and Urothelial Carcinoma

San Francisco, CA (UroToday.com) Health-related quality of life (HRQOL) reflects the patient’s subjective perception of several functional domains: physical, psychological, cognitive, social, and general well-being. HRQOL is central to assessment of efficacy and guides decision at a regulatory level, especially when drug impacts on overall survival is limited.

ASCO GU 2019: Study of Durvalumab Given with Chemotherapy, Durvalumab in Combination with Tremelimumab Given with Chemotherapy, or Chemotherapy in Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer

San Francisco, CA (UroToday.com) Bladder cancer is the ninth most common cancer diagnosis worldwide. Over 5% of patients present with metastatic disease. Approximately 70% present with non-muscle invasive disease (NMIBC) and 30% are muscle invasive (MIBC). Nearly 40% of NMIBC progress to MIBC. Combining immunotherapy with chemotherapy could be a key option for improving clinical outcomes in advanced urothelial carcinoma patients.

ASCO GU 2019: Phase II Study of Ribociclib in Men with Unresectable, Incurable Teratoma with Recent Progression

San Francisco, CA (UroToday.com) Most patients with teratoma are managed by surgery and no standard medical therapy exists for progressive and unresectable teratoma. Little progress has been made in the treatment of progressive and unresectable disease, and no standard therapy exits. Teratomas have a functional expression of retinoblastoma protein, and clinical activity was observed with CDK4/6 inhibition.1 Ribociclib is an orally bioavailable small molecule inhibitor of CDK 4/6, approved for the use in patients with hormone receptor positive, human epidermal growth factor 2 negative advanced breast cancer. Given its mechanism of action, it may have potential therapeutic activity in patients with teratomas. 

ASCO GU 2019: Malignant Pheochromocytoma: Comprehensive Genomic Profiling Study

San Francisco, CA (UroToday.com) Genomic profiling of large datasets of different malignancies has begun to reveal information beyond what basic immunohistochemistry and histology can offer. With increasing knowledge regarding the genomics of these malignancies, novel therapies are being developed and are able to be utilized across disease spaces.

ASCO GU 2019: Accelerated versus Standard BEP Chemotherapy for Adult and Pediatric Male and Female Patients with Intermediate and Poor-Risk Metastatic Germ Cell Tumors

San Francisco, CA (UroToday.com) Bleomycin, Etoposide, and Cisplatin (BEP) *4 as three weekly cycles are the standard of care first-line treatment for patients with metastatic germ cell with poor prognostic features. High dose chemotherapy and more complex regimens have failed to improve cure rates and are more toxic. Accelerating regimens of standard three weekly chemotherapy to 2-weekly cycles has improved cure rates in other malignancies. Phase 1 and 2 data have shown that it is safe and feasible to accelerate standard chemotherapy in germ cell tumors.

ASCO GU 2019: The PRIMETEST Trial: Interim Analysis of a Phase II Trial for Primary Retroperitoneal Lymph Node Dissection (RPLND) in Stage II A/B Seminoma Patients without Adjuvant Treatment

San Francisco, CA (UroToday.com) Seminoma (one of two predominant histologic subtypes of testicular cancer), when presenting with metastatic disease, specifically with isolated retroperitoneal lymphadenopathy, is typically treated with external beam radiation therapy (XRT) or systemic chemotherapy (3 cycles BEP or 4 cycles EP). There has been little change in these recommendations over the last few decades. However, with greater follow-up and interest in the long-term morbidity of these systemic therapies (toxicities often present many years), there is growing interest in alternative therapies.

ASCO GU 2019: Patients with Previously Treated Metastatic Urothelial Cancer Treated with Sacituzumab Govitecan (IMMU-132)

San Francisco, CA (UroToday.com) Patients with metastatic urothelial carcinoma (mUC) have a poor prognosis, and those who progress after platinum chemotherapy and immunotherapy with programmed death ligand 1 (PD-1)/(PD-L1) inhibitors have limited treatment options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate. The antibody is humanized anti-Trop2 and it is attached to the active metabolite of irinotecan, a cytotoxic chemotherapy agent. The combination drug targets Trop-2 which is overexpressed in aggressive epithelial cancers including up to 83% of UC.

ASCO GU 2019: Metastatic Seminomas Show Expression of Immune Related Pathways

San Francisco, CA (UroToday.com) Testis cancer is a relatively rare malignancy in men, but secondary to delayed diagnosis ~15-20% of men will present with metastatic disease. However, little is known about the molecular mechanisms resulting in tumor progression and eventually metastasis in testicular germ cell tumors. Only a few studies in other tumor types have identified a limited set of genes, related to invasion, progression or metastases to be distinctly upregulated at the invasive tumor front in metastasized patients. At the GU ASCO session on improving outcomes in rare genitourinary malignancies session, Dr. Nestler discussed regional differences in testicular germ cell tumor subtype seminoma, in order to achieve a better understanding of the mechanisms involved in the metastatic process.

ASCO GU 2019: Penile Squamous Cell Carcinoma is Genomically Similar to Other HPV-Driven Tumors

San Francisco, CA (UroToday.com) Penile squamous cell carcinoma is a rare disease in the US with 2,030 new cases and 340 deaths each year. It is also a global health issue, particularly in developing countries. HPV is responsible for ~50% of penile squamous cell carcinomas; relapsed disease is fatal after first-line treatment failure, with a median survival of 5 months. While surgery and radiation may be used for patients with loco-regional disease, unfortunately, there are limited treatment options for patients with advanced penile squamous cell carcinoma. To date, there have been no published genome-wide studies on the genetic alterations of penile squamous cell carcinomas or on the differences between HPV (+) and HPV (−) tumors. At the GU ASCO session on improving outcomes in rare genitourinary malignancies, Jad Chahoud, MD presented results of the largest whole exon sequencing analysis among patients with penile squamous cell carcinoma.

ASCO GU 2019: Point-Counterpoint: Subgroup Analyses Can Be Used to Change Clinical Practice Guidelines

San Francisco, CA (UroToday.com) The controversies in data interpretation covered an important topic for researchers, discussing the role of subgroup analyses in changing clinical practice. This panel included a biostatistician, Dr. Ludovic Trinquart and two medical oncologists: Drs. Ana Aparicio and Atish Choudhury. The discussion focused on subgroup analyses from the CHAARTED chemohormonal therapy in metastatic hormone-sensitive prostate cancer1, and radiotherapy to the primary tumor for newly diagnosed, metastatic prostate cancer (STAMPEDE arm H)2.

ASCO GU 2019: Penile Carcinoma Regional Lymph Node Involvement: Radiation Versus Surgery – Surgeon Perspective

San Francisco, CA (UroToday.com) In this presentation, Dr. Nicolai provided the surgical perspective for penile cancer regional lymph node management – and while he didn’t necessarily argue against radiation, he did note there was far more evidence to support surgery. He agrees there is a role for radiation, but what that exact role is isn’t entirely clear yet, and further data is required.

ASCO GU 2019: Practice Makes Perfect: Should All Testicular Cancer Cases Be Discussed with High-Volume Centers?

San Francisco, CA (UroToday.com) In this presentation, Dr. Nichols focuses on areas of improvement for the management of testicular cancer. “Close to perfect… far from finished” is the title of his talk,

The hypothesis and underpinning of this talk are that there is a clinically significant decrement in GCT patient outcomes in low-experience / low-volume centers. He wants to explore ways to improve or eradicate the outcome gap between high and low volume centers.

ASCO GU 2019: Penile Carcinoma Regional Lymph Node Involvement: Radiation Versus Surgery – Radiation Oncology Perspective

San Francisco, CA (UroToday.com) In this talk, the first of two talks on the topic, Dr. Hoffmann provided the radiation oncologist perspective for penile cancer regional lymph node management. As a reminder, squamous cell carcinoma of the penis, or penile cancer, has an established drainage pathway through the superficial inguinal nodes, deep inguinal nodes and then to the pelvic lymph nodes. To reflect this, the staging for penile cancer has stratified nodal staging into 4 substages – pN0 – N3, based on the presence of lymph nodes, number of lymph nodes, laterality, and mobility.

ASCO GU 2019: MicroRNA 371 As a Biomarker: Is It a Breakthrough?

San Francisco, CA (UroToday.com) Dr. Hamilton, a recognized expert in the management of testicular cancer at a high volume center (Princess Margaret Cancer Centre, Toronto), highlights the potential promise of MicroRNA 371 (miRNA 371) as a new testis cancer biomarker.

ASCO GU 2019: Whole Genome and Transcriptome Analysis of Metastatic Adrenocortical Carcinoma

San Francisco, CA (UroToday.com)  Although adrenal cortical carcinoma (ACC) is a rare malignancy, it is a rather aggressive one, with approximately 40% of patients presenting with metastatic disease. The standard of care treatment is currently a combination of etoposide/doxorubicin/cisplatin (EDP) and mitotane. Unfortunately, ACC has a poor response to cytotoxic treatment and most patients with metastatic disease show progression. 

ASCO GU 2019: Outcome of Men with Relapses after Adjuvant BEP for Clinical Stage I Nonseminoma

San Francisco, CA (UroToday.com) Clinical stage I non-seminoma is defined as disease that is limited to the testis, with no clinical or radiographic evidence of metastatic disease. It is known that men with clinical stage I seminoma have an ~15% risk of relapse if their pathology shows no evidence of lymphovascular invasion (LVI), and up to a 50% risk of relapse if LVI is present. One strategy that is commonly employed to reduce the relapse risk has been 1-2 cycles of adjuvant bleomycin/etoposide/cisplatin (BEP), which reduces the risk of relapse to ~1-3%.