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ASCO 2018

ASCO 2018

ASCO 2018: Relapse-Free Survival of Clinical T2-4N0 Urothelial Bladder Carcinoma After Radical Cystectomy, with or without Perioperative Chemotherapy: Endpoints for Clinical Trial Design.

Chicago, IL (UroToday.com) Results from several prospective trials have led to neoadjuvant chemotherapy followed by radical cystectomy being considered the gold-standard treatment for patients with muscle-invasive bladder cancer (MIBC).1 2
In a meta-analysis of 886 patients analyzed after neoadjuvant chemotherapy and radical cystectomy, the pathological complete response rate was 28.6%, leading to a relative risk for OS of 0.45 (95%CI 0.36-0.56) compared to those that did not achieve complete response3. However, data from 19 centers outside of a clinical trial suggested that pathologic complete response rates may lower in the real-world setting (23.9-24.5%) compared to clinical trials 4. As such, the full benefit of neoadjuvant therapy may not be captured via pathologic complete response rates.

ASCO 2018: Treatment of mHSPC and Implications for Subsequent Management

Chicago, IL (UroToday.com) Neeraj Agarwal provided a comprehensive overview of the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Three general topics were reviewed – the current standard of care for men with (mHSPC), the role of definitive therapy of primary prostate cancer (PC ) in the setting of mHSPC, and the implication of the upfront use of novel therapies on subsequent treatments in the setting of metastatic castrate-resistant prostate cancer (mCRPC).

ASCO 2018: Measurable Immunologic Changes and Improved Clinical Activity in mRCC with Nivolumab + Bevacizumab or Nivolumab + Ipilimumab

Chicago, IL (UroToday.com) Frontline therapy for metastatic renal cell carcinoma has changed dramatically over the past 25 years. The therapies exploit different biologic pathways which are dysregulated in RCC, including targeting vascular endothelial growth factor, fibroblast growth factor, stem-cell factor, and platelet-derived growth factor via tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors1. Immunotherapy was there at the very beginning with IL-2 – however, only a small portion of patients had a durable benefit2.

ASCO 2018: Pembrolizumab plus Enzalutamide in mCRPC: Extended Follow Up

Chicago, IL (UroToday.com) While PD-1 inhibitors have made a marked impact on the survival of many patients with solid tumors, metastatic castration-resistant prostate cancer remains challenging to treat with checkpoint inhibitors and most patients are refractory to single-agent PD-1 inhibition on clinical trials. It has been reported that patients who progress on enzalutamide have increased PD-L1/2+ dendritic cells in blood compared to those patients who are responding to therapy1. Thus, it has been hypothesized that patients who progress on enzalutamide may have a primed tumor microenvironment which may sensitive them to PD-1 inhibition.

ASCO 2018: Enzalutamide Plus CC-115 in Men with mCRPC: A Phase 1b Prostate Cancer Clinical Trials Consortium Study

Chicago, IL (UroToday.com) Enzalutamide is an oral anti-androgen receptor inhibitor which improves overall survival in men with castration-resistant prostate cancer before and after exposure to chemotherapy1,2. Overall response rates range from 29% to 60% depending on the study population with a median PFS of 19.4 months in STRIVE3. However, all patients will eventually progress on therapy, many due to AR gene rearrangements causing truncated AR splice variants that lack the AR ligand-binding domain4. Thus, additional novel therapies are necessary to modulate androgen receptor signaling. 

ASCO 2018: Perspective on Balancing Toxicities in the Treatment of mHSPC

Chicago, IL (UroToday.com) Celestia Higano, MD, gave a talk on the topic of treatment toxicities in patients with metastatic hormone-sensitive prostate cancer (MHSPC). Dr. Higano began with the most important question in this topic, on how to decide which therapy to use in MHSPC. One of the options is to decide by volume of metastatic disease. 

ASCO 2018: Long-Term Androgen Deprivation, With or Without Radiotherapy, in Locally-Advanced Prostate Cancer: Updated Results from a Phase III Randomized Trial

Chicago, IL (UroToday.com) There is a need to know whether there is a beneficial effect for the addition of external beam radiation therapy (EBRT) to long term androgen deprivation therapy (ADT), in patients with locally advanced prostate cancer. The authors of this study presented long term results (7.3 year median follow-up) of this specific trial published in 2012.1

ASCO 2018: Optimal Patient Selection/Stratification Perspective

Chicago, IL (UroToday.com) Charles Ryan, MD, gave an excellent talk on the optimal patient selection for prostate cancer. When assessing early failure and early death in studies comparing abiraterone and androgen deprivation therapy (ADT), it is evident that approximately 22% of patients are dead 2 years after starting ADT + abiraterone. This death rate rises to 33% after 3 years of follow-up.

ASCO 2018: Ten Year Treatment Outcomes of Radical Prostatectomy Vs External Beam Radiation Therapy Vs Brachytherapy for 1,503 Patients With Intermediate Risk Prostate Cancer

Chicago, IL (UroToday.com) Comparison of definitive therapy of localized prostate cancer is of great interest to both urologists, radiation oncologists and medical oncologists. In this study the authors present data on 10-year treatment outcomes of radical prostatectomy (RP) vs. external beam radiation therapy (EBRT) vs. brachytherapy (BT) for patients with intermediate risk prostate cancer (IRPC).

ASCO 2018: Optimizing Androgen Receptor Targeting Strategies Perspective

Chicago, IL (UroToday.com) Mary Ellen Taplin, MD, discussed the clinician’s perspective on optimizing androgen receptor (AR) targeting strategies. The response to androgen deprivation therapy (ADT) is different between the state of hormone-sensitive prostate cancer (HSPC) and castrate-resistant prostate cancer (CRPC) (Figure 1). 

ASCO 2018: Approaches in Management of Refractory Germ Cell Cancer

Chicago, IL (UroToday.com) Anja Lorch, MD, gave a talk on how to approach and treat refractory germ cell tumors (GCTs). Most patients with metastatic GCTs will be cured by 3-4 cycles of BEP chemotherapy. However, some patients will be refractory to this treatment. For these patients, 1st line salvage therapy has a favorable response in 60-80% of patients, with long-term survival ranging between 30-70%. In 2nd  line salvage treatment, favorable response are seen in 30-40% of patients with long-term survival ranging between 15-25%.

ASCO 2018: Long-Term Patterns in Race-specific, Distant Metastasis-free Survival Following Radiation Treatment for Prostate Cancer

Chicago, IL (UroToday.com) It is known that prostate cancer (PC) outcomes vary according to race. African Americans (AA) have a 1.5-fold greater incidence of PC and 2-fold greater mortality than Caucasian Americans (CA).
The authors of this study aimed to compare distant metastasis free survival (DMFS) of AA and CA military health care beneficiaries treated with radiotherapy for prostate cancer over a 20-year period.

ASCO 2018: Impact of Treatment Sequence on the Outcomes of Metastatic Castration Resistant Prostate Cancer Patients With Germline BRCA2 Mutations: A Subanalysis of the PROREPAIR-B Study

Chicago, IL (UroToday.com) Approximately 3-5% of metastatic castrate resistant prostate cancer patients (MCRPC) have been shown to have BRCA2 germline mutations.
PROREPAIR-B (NCT03075735) [1] is the first prospective study to report a worse survival from MCRPC patients with these associated germline mutations. This study demonstrated significant interactions between treatment-type (androgen signaling inhibitors [ASI]/Taxanes) and BRCA2 status with an effect on cause-specific survival (CSS) from 1st line (p = 0.015) and 2nd line (p = 0.006).

ASCO 2018: Survivorship and Surveillance in Management of Germ Cell Cancer

Chicago, IL (UroToday.com) Christian Kollmannsberger, MD, gave an excellent talk on survivorship and long-term surveillance in the management of germ cell tumors (GCTs). All major types of cancer therapy can result in side effects that can impair well-being, physical and psychosocial functioning, and overall quality of life. These side effects may last long after the treatment ends. In GCTs the late effects affecting mortality do not show until 20+ years of follow-up.  Ironically, the mortality from long-term complications in good/intermediate risk patients may be higher than the mortality associated with the disease itself. In fact, 20 years after cisplatin-based chemotherapy, patients have a 50% higher risk of dying from unrelated GCT causes compared to the general population.[1]

ASCO 2018: CABOPRE: Phase II Study of Cabozantinib Prior to Cytoreductive Nephrectomy in Locally Advanced and/or Metastatic Renal Cell Carcinoma

Chicago, IL (UroToday.com) The current standard of care for patients with metastatic RCC is cytoreductive nephrectomy, followed by vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy. With this type of therapy, patients need to recover from their surgery before starting TKI therapy. Up to 50% of patients do not receive TKI therapy in a timely manner.

ASCO 2018: State-of-the-Art Management of Germ Cell Cancer

Chicago, IL (UroToday.com) Darren Feldman, MD, gave an outstanding talk on practical points in the management of germ cell tumors (GCTs). Despite an increasing incidence and the fact that it is the most common cancer in men aged 15-24, GCT remains a rare disease. It is the rarity of this disease that increases the risks of errors being made. Additionally, it is noteworthy that in the last 15 years no new drugs have been approved for GCT treatment.

In this talk, Dr. Feldman reviewed some common and important principles and pitfalls in diagnosis and workup, early-stage disease, and advanced disease.

ASCO 2018: PROPHECY - A Prospective Trial of Circulating Tumor Cell AR-V7 Detection in mCRPC with Abiraterone or Enzalutamide

Chicago, IL (UroToday.com) Enzalutamide and abiraterone improve progression-free survival and overall survival in men with metastatic castration-resistant prostate cancer1,2. However, a small proportion of men have primary resistance to enzalutamide or abiraterone, and essentially all men develop secondary resistance3.

ASCO 2018: NIVES study: A Phase II Trial of Nivolumab Plus Stereotactic Body Radiotherapy in II And III Line of Patients with Metastatic Renal Cell Carcinoma

Chicago, IL (UroToday.com) There have been great advances in the medical treatment of patients with metastatic RCC (MRCC). However, despite these significant advances, the 5-year survival rate of these patients is still approximately 10%. Stereotactic body radiotherapy (SBRT) is a focused radiotherapy, delivering high dose radiation directly to the tumor. Its advantage is that it destroys more tumor cells and causes less damage to adjacent healthy tissue.

ASCO 2018: Leveraging Social Media to Advance Cancer Research: Challenges and Opportunities

Chicago, IL (UroToday.com) Mina Sedrak, MD, discussed the challenges and opportunities to leverage social media to advanced cancer research. Over the last decade, social media adoption has increased substantially, with 5% of adults in the US having at least one social media site in 2006 to 69% in 2018. Furthermore, health-related social media activities are on the rise, with the use of disease-specific hashtags, such as prostate cancer (#pcsm), kidney cancer (#kcsm), and bladder cancer (#blcsm) for incorporating better streamlining of information.

ASCO 2018: KEYNOTE-199: Pembrolizumab for docetaxel-refractory Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Chicago, IL (UroToday.com) Early anti PD-1 studies with prostate cancer have had mixed results.  In the first study of PD-1 blockade in prostate cancer, 0% (0/17) of patients had an objective response1. However, in a subsequent study (KEYNOTE-028), the cohort of patients with prostate cancer had a 13% (3/23) overall response rate with an impressive median duration of response of 59 weeks2. During this ASCO, Julie Nicole Graff, MD, presented data on pembrolizumab in combination with enzalutamide in patients who progressed on enzalutamide, which demonstrated a 25% (3/12) radiographic response rate3.