ASCO 2019

ASCO 2019

ASCO 2019: Vofatamab in Combination with Pembrolizumab in WT Metastatic Urothelial Carcinoma: FIERCE-22

Chicago, IL (UroToday.com) Patients with metastatic urothelial carcinoma (mUC) who have failed platinum-based chemotherapy have a poor prognosis. Currently, second-line therapies are immune checkpoint inhibitors – but reported response rates to immune checkpoint inhibitors (ICI) are approximately 20%, as seen below:

ASCO 2019: IMmotion151 Subgroup Analysis: Atezolizumab + Bevacizumab versus Sunitinib in Patients with Untreated Metastatic Renal Cell Carcinoma and Sarcomatoid Histology

Chicago, IL (UroToday.com) The landscape of systemic therapy for metastatic renal cell carcinoma (mRCC) is rapidly changing. Beyond the addition of immune checkpoint inhibitor combinations (nivo/ipi) and additional tyrosine kinase innhibitors (TKIs) (cabozantinib), there are now combination therapies that are demonstrating excellent responses rates in the first line. The recent data from KEYNOTE‑426 has led to approval of axinitib/pemrbolizumab in the first line for mRCC, and as can be expected from this combination, seems to have efficacy for good, intermediate and poor risk patients.

ASCO 2019: Patient-Reported Outcomes in IMmotion150: Atezolizumab alone or with Bevacizumab versus Sunitinib in First-Line Metastatic Renal Cell Carcinoma

Chicago, IL (UroToday.com) The landscape of systemic therapy for metastatic renal cell carcinoma (mRCC) is rapidly changing. Beyond the addition of immune checkpoint inhibitor combinations (nivo/ipi), additional TKI’s (cabozantinib), there are now combination therapies that are demonstrating excellent responses rates in the first line. The recent data from KEYNOTE‑426 has led to the approval of axinitib/pemrbolizumab in the first line for mRCC, and as can be expected from this combination, it seems to have efficacy for good, intermediate and poor risk patients.

ASCO 2019: CheckMate 214 Post-Hoc Analyses of Nivolumab plus Ipilimumab or Sunitinib in IMDC Intermediate/Poor-Risk Patients with Previously Untreated Advanced Renal Cell Carcinoma with Sarcomatoid Features

Chicago, IL (UroToday.com) The landscape of systemic therapy for metastatic renal cell carcinoma (mRCC) is rapidly changing. Beyond the addition of immune checkpoint inhibitor combinations (nivo/ipi), additional tyrosine kinase inhibitors (TKIs) (cabozantinib), there are now combination therapies that are demonstrating excellent responses rates in the first line.

ASCO 2019: Efficacy of Immune Checkpoint Inhibitors and Genomic Characterization of Sarcomatoid and/or Rhabdoid Metastatic Renal Cell Carcinoma

Chicago, IL (UroToday.com) The landscape of systemic therapy for metastatic renal cell carcinoma (mRCC) is rapidly changing. Beyond the addition of immune checkpoint inhibitor combinations (nivo/ipi), additional TKI’s (cabozantinib), there are now combination therapies that are demonstrating excellent responses rates in the first line. The recent data from KEYNOTE‑426 has led to the approval of axitinib/pembrolizumab in the first line for mRCC, and as can be expected from this combination, seems to have efficacy for good, intermediate and poor risk patients.

ASCO 2019: Biomarkers of Outcomes in a Randomized Phase II trial of first-line paclitaxel, ifosfamide, and Cisplatin versus Bleomycin, Etoposide, and Cisplatin for Intermediate- and Poor-Risk Germ Cell Tumors

Chicago, IL (UroToday.com) In a multicenter phase 2 randomized controlled trial of first-line Paclitaxel, ifosfamide and cisplatin (TIP) vs. bleomycin, etoposide and platinum (BEP) chemotherapy for patients with intermediate or poor risk germ cell tumor (GCT), there was no difference in the favorable response rate (FRR).¹ Prior studies demonstrated the prognostic importance of tumor marker decline in advanced GCT patients receiving BEP.^2-4 AKT and proteins involved in DNA damage repair (DDR) have been postulated to correlate with cisplatin sensitivity.^{5, 6}

ASCO 2019: Targeted Therapeutics and Patient Selection in Advanced Urothelial Carcinoma

Chicago, IL (UroToday.com) Yohann Loriot, MD, MSc, provided a summary and analysis of 3 abstracts:

Abstract 4509: A phase II study of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma, Xinan Sheng
Abstract 4510: Infigratinib in upper tract urothelial carcinoma vs urothelial carcinoma of the bladder and association with comprehensive genomic profiling/cell-free DNA results, Nazli Dizman
Abstract 4511: FIERCE-22: Clinical activity of vofatamab (V) a FGFR3 selective inhibitor in combination with pembrolizumab (P) in WT metastatic urothelial carcinoma, preliminary analysis, Arlene O. Siefker-Radtke

ASCO 2019: Radical Prostatectomy with or without Neoadjuvant Chemohormonal Therapy in Men with Clinically Localized, High-Risk Prostate Cancer - CALGB 90203 (Alliance)

Chicago, IL (UroToday.com) James Andrew Eastham MD, on behalf of his coauthors, presented the results of the CALGB 90203 Alliance study. He presented this earlier at AUA 2019 but presents it again to a wider audience here at ASCO 2019.

ASCO 2019: KEYNOTE-427 Cohort B: First-Line Pembrolizumab Monotherapy for Advanced Non‒Clear Cell Renal Cell Carcinoma

Chicago, IL (UroToday.com) Most renal cell carcinomas (RCC) are clear cell (80%).¹ The clinical trial data for non-clear cell RCC (nccRCC) is, therefore, limited.² The treatment guidelines for advanced nccRCC recommend enrollment in clinical trials or the use of the vascular endothelial growth factor inhibitor, sunitinib.³ There is an unmet need for a safe and effective treatment for advanced nccRCC patients. Therapies targeting the PD-1 pathway appear promising for clear cell RCC,² but there is limited known data on the efficacy of a single agent PD-1 checkpoint inhibitor therapy in nccRCC.

ASCO 2019: First-Line Pembrolizumab Monotherapy in Advanced Clear Cell Renal Cell Carcinoma: Updated Results for KEYNOTE-427 Cohort A

Chicago, IL (UroToday.com) Interactions between programmed death 1 (PD-1) and its ligands, PD-L1, PD-L2 on tumors cells can effectively “disarm” host immune function, allowing tumors to escape immune surveillance.¹ To date, several PD-1 or PD-L1 based combination regimens have received FDA approval as first-line treatment for renal cell carcinoma (RCC).^2-8 The potential usefulness of a single agent PD-1 blockade in treatment-naïve clear-cell RCC (ccRCC) patients is unknown.

ASCO 2019: A Multicentric Phase II Randomized Trial of Docetaxel plus Enzalutamide versus Docetaxel as First-line Chemotherapy for Patients with Metastatic Castration-resistant Prostate Cancer: CHEIRON Study

Chicago, IL (UroToday.com) Docetaxel and enzalutamide, along with abiraterone, are FDA approved therapies for the treatment of metastatic castration-resistant prostate cancer (mCRPC). TAX327 was the landmark study which demonstrated that docetaxel could improve overall survival, response to pain, serum PSA, and quality of life over mitoxantrone in patients with mCRPC.¹

ASCO 2019: Classification and Management of Infrequent Genitourinary Malignancies

Chicago, IL (UroToday.com) Samuel A. Funt, MD, provided a summary and analysis of 3 abstracts at ASCO 2019. In this presentation, he focused on filling in the knowledge gaps for patients with metastatic urothelial cancer.

ASCO 2019: Balancing Disease Control and Quality of Life in Metastatic Renal Cell Carcinoma

Chicago, IL (UroToday.com) In this presentation, Neeraj Agarwal, MD, focused on balancing disease control and quality of life in patients with metastatic renal cell carcinoma. Dr. Agarwal summarized three abstracts.

ASCO 2019: Sarcomatoid RCC: Defining a New Treatment Paradigm?

Chicago, IL (UroToday.com) James Brugarolas, MD, PhD, summarized 3 presentations — abstracts 5412, 4513, and 4514 — all focused on sarcomatoid histology within renal cell carcinoma (RCC), and in the last abstract, included rhabdoid histology.

Janssen Seeks to Expand Use of ERLEADA® (apalutamide) in the Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer

San Francisco, CA (UroToday.com) -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced the submission of a Type II variation to the European Medicines Agency (EMA) seeking approval of ERLEADA® (apalutamide) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), regardless of extent of disease or prior docetaxel treatment history. The submission is based on findings from the Phase 3 TITAN study which were presented at the 2019 American Society of Clinical Oncology (ASCO ) Annual Meeting and simultaneously published online in The New England Journal of Medicine.^1,2

ASCO 2019: Clinical Outcomes According to PD-L1 Status and Age in the Prospective International SAUL Study of Atezolizumab for Locally Advanced or Metastatic Urothelial Carcinoma or Non-UC of the Urinary Tract

Chicago, IL (UroToday.com) Atezolizumab is a monoclonal antibody targeting PD-L1 that has been one of the primary immune checkpoint inhibitors leading the immune-checkpoint inhibitor (ICI) wave. In the setting of bladder cancer, it is an approved therapy for locally advanced/metastatic urothelial carcinoma (UC) based on IMvigor210 and IMvigor211 phase II and III trials.^1,2

Following its approval, the single-arm SAUL³ study looked at a broader generalized patient population and found that it had a median overall survival (OS) of 8.7 months and a safety profile consistent with previous atezo trials.

ASCO 2019: First-Line Immuno-oncology Combination Therapies in Metastatic Renal-cell Carcinoma: Results from the International mRCC Database Consortium

Chicago, IL (UroToday.com) In metastatic renal cell carcinoma (mRCC) several first-line immuno-oncology combination therapies have been demonstrated to have improved outcomes vs. sunitinib monotherapy. Comparative data between ipilimumab/nivolumab (IPI/NIVO) and immune-oncology-VEGF (IO-VEGF) inhibitor combinations are limited. Additionally, the use and effectiveness of second-line therapies following progression on first line immune-oncology combination treatments remains unknown.

ASCO 2019: Atezolizumab + Bevacizumab Versus Sunitinib in Patients with Untreated Metastatic Renal Cell Carcinoma and Sarcomatoid Histology: IMmotion151 Subgroup Analysis - Medical Oncologist Perspective

Chicago, IL (UroToday.com) IMmotion 151 was a randomized phase III study evaluating atezolizumab plus bevacizumab versus sunitinib for patients with mRCC with either clear cell or sarcomatoid histologies. 915 patients were enrolled and 40% of patients had PD-L1 positive disease. After a median of 24 months follow up, the median progression-free survival (PFS) was 11.2 months in the atezolizumab plus bevacizumab group, compared to 7.7 months in the sunitinib group.¹ In terms of overall survival (OS), there was no significant difference in the intention to treat analysis - median overall survival had a hazard ratio (HR) of 0.93 (95%CI 0.76–1.14). This abstract focuses on the subgroup of patients with sarcomatoid features on histology.

ASCO 2019: Updated Approaches to Treatment Sequencing in the Era of M0 CRPC Approvals

Chicago, IL (UroToday.com) This session was set up and moderated by Mark Fleming, MD, with a specific focus on the general medical oncologist (and urologist). The structure was that of a case presentation, with breaks for discussion and audience participation. Below, I summarize the discussion and the panelists’ input, as well as audience response to the questions asked. As there were no formal presentations by each of the panelists, the topics below are not attributed to any one individual.

ASCO 2019: Infigratinib in Upper Tract Urothelial Carcinoma vs Urothelial Carcinoma of the Bladder and Association with Comprehensive Genomic Profiling/Cell-free DNA Results

Chicago, IL (UroToday.com) Infigratinib (BGJ398) is a potent and selective FGFR1–3 inhibitors with significant activity in patients (pts) with advanced or metastatic urothelial carcinoma (mUC) bearing FGFR3 alterations. In a study by Pal et al.¹ 67 cisplatin-ineligible mUC patients with FGFR3 mutations were treated with BGJ398 orally at 125 mg/day on 3 weeks on, 1 week off schedule until unacceptable toxicity or progression. Among 67 patients treated, an overall response rate of 25.4% was observed and an additional 38.8% of patients had disease stabilization, translating to a disease control rate of 64.2%.