ASCO GU 2019

ASCO GU 2019: Value-Based Decision-Making for Castrate-Sensitive Prostate Cancer

San Francisco, CA (UroToday.com) In this second talk of the session on quality and value for optimizing advanced prostate cancer treatment, Dr. Chen gave a presentation on value-based decision making for castration-sensitive prostate cancer.

Seattle Cancer Care Alliance Physicians to Present their Research at Genitourinary Cancers Symposium

San Francisco, CA (UroToday.com) -- Seattle Cancer Care Alliance (SCCA), UW Medicine, and Fred Hutch physicians and researchers who are leaders in treating genitourinary cancers will attend and present their research at the Genitourinary Cancers Symposium taking place Feb. 14-16 in San Francisco. The symposium will feature an array of multidisciplinary sessions covering prostate, renal, urothelial, penile, testicular, and adrenal cancers. World-renowned faculty, including our own, will discuss the latest clinically relevant topics with a focus on multimodality therapy and value in cancer care.

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: Phase 3 Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Metastatic Hormone-Sensitive Prostate Cancer: The ARCHES Trial

San Francisco, CA (UroToday.com) Enzalutamide (ENZA) is an androgen receptor signaling inhibitor which inhibits the androgen receptor signaling pathway by blocking the binding of androgen to the androgen receptor as well as inhibition of nuclear translocation of the androgen receptor.¹ Enzalutamide has been shown to be effective in improving overall survival in patients with metastatic castration resistant prostate cancer (mCRPC) both before and after chemotherapy.^2,3First in 2012, AFFIRM showed in a population of post-chemotherapy mCRPC patients that enzalutamide improved overall survival compared with placebo (18.4 months vs 13.6 months, HR 0.63, p<0.001), which led to its first FDA approval in prostate cancer.² Next in 2014, PREVAIL showed that enzalutamide was able to decrease the risk of radiographic progression and death and delay chemotherapy which broadened its FDA approval to all patients with mCRPC.³ Most recently, based on the results of PROSPER which showed that enzalutamide significantly reduced the risk of developing M1 CRPC by prolonging metastasis-free survival (36.6 vs 14.7 months), enzalutamide gained an FDA indication in 2018 for use in men with non-metastatic CRPC with a PSA doubling time of less than 10 months.⁴This study aims to provide evidence for the only space left untouched by enzalutamide – metastatic castration sensitive prostate cancer.

ASCO GU 2019: Phase II Trial of Pembrolizumab for Patients with High-Risk Non-Muscle Invasive Bladder Cancer Unresponsive to BCG

San Francisco, CA (UroToday.com) The primary management for non-muscle invasive bladder cancer is surgical resection via transurethral resection of bladder tumor (TURBT). Unfortunately, many patients will have disease recurrence or progression. According to the European Organization for Research and Treatment risk tables (EORTC), after a median follow up of 3.9 years, 47.8% had at least one recurrence with a median time to first recurrence of 2.7 years, and 11% of patients had progression to muscle-invasive disease.¹ For low-risk patients, a single dose of intravesical chemotherapy or surveillance may be sufficient. However, for high-risk patients, first line intravesical Bacillus Calmette-Guerin (BCG) therapy is standard of care, as recommended by the American Urological Association (AUA), the European Association of Urology (EAU), and the Canadian Urological Association (CUA) bladder cancer guidelines.^2-4

ASCO GU 2019: Results from KEYNOTE-427 Cohort B: First-line Pembrolizumab Monotherapy for Advanced Non-Clear Cell Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Non-clear cell renal cell carcinoma represents up to 25% of patients with renal cell carcinoma.¹ The majority of patients will have papillary RCC (15%) or chromophobe (5%), but several other types exist including collecting duct carcinoma, medullary carcinoma, translocation, and unclassified RCC.

ASCO GU 2019: Phase III CheckMate 214 Trial of First-Line Nivolumab + Ipilimumab or Sunitinib in Patients with Advanced Renal Cell Carcinoma with Thirty Month Follow Up Results

San Francisco, CA (UroToday.com) Checkmate 214 revolutionized front-line treatment of patients with intermediate or poor risk metastatic renal cell carcinoma (mRCC) by introducing combination immunotherapy ipilimumab and nivolumab. In the original New England Journal of Medicine publication in 2018, at a median follow up of 25.2 months, the 18-month overall survival was 75% with ipi/nivo compared with 60% with sunitinib for patients with intermediate or poor risk features, and the objective response rate was 42% vs 27% (p<0.001) with an impressive 9% complete response rate,¹ which led to FDA approval of ipi/nivo in April 2018 and EMA approval in 11/2018. This abstract provides an update to the original data with 30 month follow up results.

ASCO GU 2019: Final analysis from the NIVOREN GETUG AFU 26 study — Safety and Efficacy of Nivolumab in Metastatic Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Immune checkpoint inhibitors have changed the treatment paradigm of metastatic renal cell carcinoma (mRCC), both in the front line and second line settings. Nivolumab, a humanized IgG4 anti-PD-L1 monoclonal antibody, is approved in both settings, based on CheckMate 214 (in combination with ipilimumab) in the first line, and CheckMate 025 in the second line.^{^1,2}

ASCO GU 2019: Phase III KEYNOTE-426 Study: Pembrolizumab plus Axitinib versus Sunitinib as First-Line Therapy for Locally Advanced or Metastatic Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Combination vascular endothelial growth factor (VEGF) inhibition with immunotherapy has shown promising results in several phase I/II studies. During ASCO 2018, Dr. Lee et al presented a study of 30 patients with metastatic renal cell carcinoma (mRCC) who were treated with Pembrolizumab and Levantinib, and this combination yielded an overall response rate of 66.7% by RECIST v1.1 and irRECIST with a median duration of response of 18.4 months.¹ 97% of patients experienced some tumor size reduction from baseline. A phase II study of Avelumab plus axitinib was presented at 2017 ASCO and this combination achieved an ORR of 58.20%.² Preliminary data regarding the combination of pembrolizumab and axitinib was initially presented at GU ASCO 2018, and out of 52 patients, 73.1% of patients had an objective response with a median PFS of 20.9 months.³ This abstract provides the phase III update to that data.

ASCO GU 2019: A Phase II Study CALYPSO: The Safety and Efficacy of Savolitinib and Durvalumab in Metastatic Papillary Renal Cancer

San Francisco, CA (UroToday.com) The most common non-clear cell renal cell carcinoma is papillary renal cell carcinoma (pRCC). pRCC accounts for 15-20% of RCC and are subcategorized into Type 1 and Type 2. Type 1 pRCC are typically associated with MET alterations whereas Type 2 pRCC typically are found to have alterations in SETD2, TFE3, and CDKN2A.¹

ASCO GU 2019: Outcomes of Patients with Metastatic Clear Cell RCC Treated with Second Line VEGFR-TKI After First Line Immune Checkpoint Inhibitor

San Francisco, CA (UroToday.com) Since the publication of CheckMate 214, immune checkpoint inhibitors (ICIs) have entered the first line space for the treatment of metastatic RCC¹. However, the majority of patients do not have an objective response to ICI and will have either primary or secondary resistance. Standard of care second line therapies involves VEGFR-TKIs, but little is known about their efficacy after ICI treatment. This study seeks to address this knowledge gap by providing a multicenter experience of treatment of mRCC after ICI therapy.

ASCO GU 2019: Pembrolizumab in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer

San Francisco, CA (UroToday.com) Immune checkpoint inhibition for prostate cancer has been met with significant challenges in the immunotherapy era. Unlike the dramatic and responses seen in melanoma, lung, kidney, and bladder cancer, prostate cancer has not had the same success in unselected patients. Even in patients with MSI high (microsatellite instability) disease, 7/11 patients did not have an objective response and 5/6 did not have a PSA50 (decline in PSA by 50%)¹. This study evaluates the off-label use of pembrolizumab in a heavily pre-treated population of patients with mCRPC.

ASCO GU 2019: Questions and Lessons Moving Forward from CARMENA: Which Treatment First? Surgeon’s Perspective

San Francisco, CA (UroToday.com) Dr. Russo gave the surgeon’s perspective of cytoreductive nephrectomy. The role and rationale for cytoreductive nephrectomy (CN) is multi-fold:

Remove a large, potentially immunosuppressive tumor that is a potential source of metastases and paraneoplastic syndromes
Palliate local symptoms of pain or bleeding that could complicate/interrupt systemic therapy
Obtain accurate pathologic subtyping to guide therapy
Should never be done to induce spontaneous metastatic tumor regression (it is a real event, but rare)

ASCO GU 2019: Questions and Lessons Moving Forward from CARMENA: Which Treatment First? Medical Oncologist’s Perspective

San Francisco, CA (UroToday.com) Dr. Harshman gave the Medical Oncologist perspective of cytoreductive nephrectomy (CN) . As has been the case for many of these debates recently, there wasn’t much of a debate – both medical oncologists and urologists have been on the same page!

ASCO GU 2019: Informing the Decision Using Data Science

San Francisco, CA (UroToday.com) In this first talk of the point-counterpoint session, Dr. Psutka reviews the literature informing the decision to expand the use of partial nephrectomy to larger, more complex masses, effectively titled “extended partial nephrectomy” (ePN).

To begin, the only Level 1 evidence supporting the oncologic efficacy PN compared to RN is the EORTC study by van Poppel et al. (EU 2007). However, it was underpowered and had significant cross-over.

ASCO GU 2019: Quality Metrics in Kidney Cancer Care

San Francisco, CA (UroToday.com) The last session of GU ASCO 2019, How Can We Better Treat Kidney Cancer, started with Dr. John Gore presented quality metrics in kidney cancer care. Dr. Gore notes that quality measurement entails several processes, including effectiveness, efficacy, equity, patient-centeredness, safety, and timeliness. Dr. Gore then mentioned that health care value is disparate in the United States, considering that the country has the highest per-capita spending per person for health care ($9,892), but is 27^th in life expectancy (78.8 years). By comparison, Japan is 15^th in spending ($4,519) and 1^st in life expectancy (83.9 years).

ASCO GU 2019: Outcomes for Avelumab Plus Axitinib versus Sunitinib in Advanced RCC - JAVELIN Renal 101: A Subgroup Analysis

San Francisco, CA (UroToday.com) The first line treatment for mRCC disease space is rapidly changing, including the first reporting of JAVELIN Renal 101 at ESMO 2018 comparing avelumab plus axitinib versus sunitinib. Highlights of this first analysis included a longer progression-free survival (PFS) (median, 13.8 vs 8.4 months; HR 0.69; p=0.0001) and better objective response rate (ORR) (51% vs 26%) for combination avelumab plus axitinib versus sunitinib in patients with previously untreated advanced/metastatic RCC.

ASCO GU 2019: Kidney Cancer Case-Based Panel: Localized Disease

San Francisco, CA (UroToday.com) The case-based discussion of kidney cancer patients featured a multi-disciplinary team including urologists, medical oncologists, and interventional radiologists. Dr. Peter Clark chaired the localized kidney cancer panel, presenting several cases from his practice for discussion.

ASCO GU 2019: When to Obtain Genetic Testing for Syndromic Renal Cell Cancer

San Francisco, CA (UroToday.com) Dr. Brian Shuch provides a summary and guide to genetic testing for syndromic renal cell carcinoma (RCC). There is an established strong inheritance pattern in kidney cancer, and now there are 15+ recognized monogenic (single-gene related) syndromes (seen in the list below). More importantly, there are complex inheritance patterns due to SNPs in patients without monogenic syndromes.

ASCO GU 2019: Phase II Trial of Nivolumab Plus Ipilimumab in Patients with SMARCB1 Deficient Kidney Malignancies

San Francisco, CA (UroToday.com) Last year, CheckMate 214 reported a significant overall survival (OS) benefit for intermediate and poor risk mRCC patients with combination nivolumab plus ipilimumab vs sunitinib¹. Given these encouraging outcomes, the search for additional applications of this combination therapy is ongoing. The potent tumor suppressor SMARCB1 (also known as INI-1, hSNF5, or BAF47) is inactivated in all cases of renal medullary carcinoma and renal cell carcinoma unclassified with medullary phenotype, as well as most malignant rhabdoid tumors of the kidney.

ASCO GU 2019

ASCO GU 2019

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