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Updates in Advanced Kidney Cancer, A Welcome Letter from the Editor

Pedro Barata | June 22, 2022

Welcome to UroToday’s new Advanced Kidney Cancer Center of Excellence. It is my great honor and pleasure to serve as its editor. Therapies for advanced kidney cancer are rapidly evolving, which can make it challenging to stay current with new developments. This website curates clinically relevant content in a variety of formats, including peer-to-peer video conversations between experts, articles and commentaries by physician-scientists, in-depth conference coverage, and newly released abstracts.

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Pedro Barata, MD, MSc

Dr. Pedro C. Barata is Board Certified in Internal Medicine and a Medical Oncologist with a focus in genitourinary tumors and clinical trials. He leads the Clinical GU Medical Oncology Research Program at the University Hospitals Seidman Cancer Center and is an Associate Professor of Medicine at Case Western University. He earned his medical degree from the New University of Lisbon in 2009 and completed his medical oncology training in 2016. After completion of his fellowship, he was invited to join the genitourinary group at Taussig Cancer Center, where he worked as a clinical fellow in genitourinary malignancies. Dr. Barata moved to Tulane University to continue his clinical and research work in the GU field and to help expand the genitourinary program offered at Tulane Cancer Center, with a focus on clinical trials. In September of 2022, Dr Barata moved to his current position at the University Hospitals Seidman Cancer Center in Cleveland, Ohio. Dr. Barata has authored or co-authored dozens of publications in high-quality and pubmed-indexed journals. In addition, he has presented multiple abstracts at important national and international meetings and has won multiple prestigious awards, including the Tulane Career Development Award, Clinical Sciences (2021). He serves as a reviewer for prestigious peer-reviewed journals, such as JAMA Oncology, Cancer, Lancet Oncology, ASCO and Journal of Global Oncology and is the Prostate Section Editor of the Oncologist journal and a member of the Editorial Board of the Translation Oncology.

Videos
Clinical Conversations by Experts
Triplet Therapy With Cabozantinib, Nivolumab, and Ipilimumab as First-line Treatment in Patients With Advanced Renal Cell Carcinoma, COSMIC 313 - Toni K. Choueiri
Adding Fecal Microbiota Transplantation (FMT) in Combination with Immunotherapy to Treat Renal Cell Carcinoma, The PERFORM Study - Ricardo Fernandes
OMNIVORE - Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma, Journal Club - Christopher Wallis & Zachary Klaassen
Final Results of TITAN-RCC Trial - Is a Tailored Approach of Nivolumab and Nivolumab/Ipilimumab as Immunotherapeutic Boost Recommended - Marc-Oliver Grimm
The First Neoadjuvant Trial Using Combination Immune Checkpoint Inhibitor and VEGF Inhibitor in Patients With Locally Advanced High-Risk RCC (NeoAvAx) – Axel Bex
The Upcoming 2022 European International Kidney Cancer Symposium - Samra Turajlic
KEYNOTE-564 30-Month Follow-Up of Pembrolizumab as Post Nephrectomy Adjuvant Therapy for Patients with Renal Cell Carcinoma - Toni Choueiri
Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma, The CLEAR Trial Journal Club - Christopher Wallis & Zachary Klaassen
Health-Related Quality of Life Assessment for Patients With Advanced or Metastatic Renal Cell Carcinoma in the CLEAR Trial – Bradley McGregor
VEGF Blockade and Combination Therapeutic Options in Advanced Renal Cell Carcinoma - Andrea Apolo
Investigator Initiated Phase I Dose-escalation Trial and 7 Subsequent Expansion Cohorts - Andrea Apolo
Efficacy Assessment of Multiple MET Kinase Inhibitors in Metastatic Papillary Renal Cell Carcinoma - The SWOG1500 PAPMET Trial - Sumanta Pal & Toni Choueiri
Frontline Treatment in Advanced Kidney Cancer - Bradley McGregor
Innovative Research for Advanced Kidney Cancer - David Braun
First-line Therapy Options for Metastatic Renal Cell Carcinoma - Tian Zhang
The Landscape of Systemic Therapy for Metastatic Renal Cell Carcinoma - Petros Grivas
The Dynamic Landscape of mRCC and the PDIGREE Trial - Tian Zhang
Newly Approved Treatment Options for the Management of Metastatic Kidney Cancer- Lauren Harshman and Toni Choueiri
Advances of Systemic Treatments in Renal Cell Carcinoma - Jens Bedke
Targeted Therapies with Immunotherapies In Kidney Cancer - Thomas Powles
Rapidly Evolving Landscape in Metastatic Renal Cell Carcinoma- Rana McKay
Frontline Data from Keynote 426 - Sandy Srinivas
Paradigm Changing Data for Kidney Cancer - Primo Lara
Patient Advocacy and Resources in Kidney Cancer - Dena Battle
Monitoring Treatment Toxicities in Patients with Renal Cell Carcinoma: discussion with Dan George and Tian Zhang
Evolution of the NCCN Guidelines for Kidney Cancer -Tian Zhang
ASSET, A Pilot Study Using Exercise Physiology in Advanced Renal Cell Carcinoma - Mike Harrison
A Review of Adjuvant Studies in Advanced Renal Cell Carcinoma - Tian Zhang
CABOSUN Trial Plus an In-depth Discussion of Kidney Cancer Treatments - Toni Choueiri
CARMENA: Practice Changing Strategies for Kidney Cancer
Discussion of the IMmotion 151 Trial: Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma - Thomas Keane
Discussion of the CABOSUN trial - Advanced Renal Cell Carcinoma - Thomas Keane
Physician-Scientist Review Articles
State of the Evidence Review Articles
Written by Christopher J.D. Wallis, MD, PhD, and Zachary Klaassen, MD, MSc
March 31, 2021
Cancers of the kidney and renal pelvis (when considered in aggregate despite different histology) represent the 6th most common newly diagnosed tumors in men and 8th most common in women in the United States in 20201, representing an estimated 73,750 new diagnoses and 14,830 deaths.
Written by Jason Zhu, MD
January 29, 2019
Kidney cancer represents 5% of all new cancer diagnoses in the United States, with approximately 64,000 new cases and 14,970 deaths in 2018.1,2 The most common type of kidney cancer is renal cell carcinoma (RCC) and the most common histologic subtype of RCC is clear cell RCC, accounting for over 80% of cases.3
Written by Christopher J.D. Wallis, MD, PhD
January 21, 2019
As highlighted in prior articles on the Etiology and Epidemiology of Kidney Cancer, cancers of the kidney and renal pelvis comprise the 6th most common newly diagnosed tumors in men and 10th most common in women1 and account for an estimated 65,340 people new diagnoses and 14,970 cancer-related deaths in 2018 in the United States.
Written by Jason Zhu, MD
November 29, 2018
Kidney cancer is the 12th most common cancer in the world, with over 300,000 new cases annually, of which 65,340 new cases will be diagnosed in the United States in 2018.1 The incidence of renal cell carcinoma (RCC) varies substantially based on the country – rates of RCC are higher in Europe and North America and much lower in Asia and South America.2
Physician-Scientist Commentaries
State of the Evidence Review Articles
Written by Matthew D. Tucker, MD
Immunotherapy-based combinations have had a dramatic improvement in outcomes for patients with metastatic renal cell carcinoma, with some patients having deep and durable responses. Developing biomarkers to predict which patients are most
Written by Zhamshid Okhunov, MD
Department of Urology, University of California, Irvine Urology
Though nephrectomy is the gold standard treatment for renal cell carcinoma, 20%-40% of patients have a recurrence and 20-30% of patients present with metastatic disease1.
Written by Zhamshid Okhunov, MD
Department of Urology, University of California, Irvine Urology
Partial nephrectomies are the standard of care with treatment of T1a or T1b tumors due to their better functional outcomes and decrease cardiovascular morbidity.
Written by Zhamshid Okhunov, MD
Department of Urology, University of California, Irvine Urology
Laparoscopic renal surgery (LRS) has long been recognized for its improvements over open renal surgery for patient quality of life.
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Toni K. Choueiri, MD
The Presidential Symposium III at the ESMO Annual Congress, Dr. Chouieri presented highly awaited results from the COSMIC-313 trial, examining the role of triplet therapy with cabozantinib, nivolumab and ipilimumab as first-line treatment in patients with advanced renal cell carcinoma (aRCC).
Presented by Kate Young, MD
Following presentations from Dr. Camillo Porta discussing updated results from the CLEAR trial on outcomes of the combination of Lenvatinib and pembrolizumab as first-line therapy in advanced renal cell carcinoma (RCC) and from Dr. Grimm discussing a tailored approach using nivolumab either as monotherapy or in combination with ipilimumab in metastatic RCC, Dr. Young provided an invited discussion to contextualize these results in the Mini Oral session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers.
Presented by Marc-Oliver Grimm, MD
At the ESMO Annual Congress focusing on non-prostate genitourinary cancers, Dr. Grimm presented the final results of the TITAN-RCC trial, assessing a tailored approach to systemic therapy in patients with metastatic renal cell carcinoma (mRCC).
Presented by Camillo G. Porta, MD, Professor, Bari, Italy
In the Mini Oral session of the ESMO Annual Congress focusing on non-prostate genitourinary cancers, Dr. Porta provided an updated analysis of the CLEAR trial examining the role of the combination of lenvatinib and pembrolizumab, as compared to sunitinib, as first-line therapy in advanced renal cell carcinoma (aRCC).
Presented by Thomas Powles, MD
The 2022 ASCO annual meeting featured a poster discussion session on kidney and bladder cancer, including a presentation by Dr. Tom Powles discussing an analysis of progression after first subsequent therapy in KEYNOTE-426, which tested pembrolizumab + axitinib versus sunitinib as first-line therapy for advanced clear cell RCC.
Presented by Eric Jonasch, MD,
The 2022 ASCO annual meeting featured a session on kidney and bladder cancer, including a presentation by Dr. Eric Jonasch discussing updated results of the LITESPARK-004 phase 2 study of belzutifan, an oral hypoxia-inducible factor 2α inhibitor (HIF-2α), for von Hippel-Lindau (VHL) disease.
Presented by Daniel Shapiro, MD
The 2022 American Urological Association (AUA) Annual Meeting included the Society of Urologic Oncology (SUO) session and a presentation by Dr. Daniel Shapiro discussing the role of cytoreductive nephrectomy in 2022.
Presented by Will Ince, FRCR, MRCP, MRCGP, MB BS
The 2022 International Kidney Cancer Symposium (IKCS) European Annual meeting included an oral abstract session and presentation by Dr. Will Ince discussing the real world impact of immune checkpoint inhibitors on survival in metastatic RCC.
Presented by Laurence Albiges, MD, PhD,
In the sixth session of the 2022 International Kidney Cancer Symposium (IKCS): Europe meeting focusing on later-lines of systemic therapy in advanced kidney cancer, Drs. Camillo Porta and Laurence Albiges debated the approach to second-line therapy in metastatic renal cell carcinoma (mRCC). 
Presented by Camillo Porta, MD
In the sixth session of the 2022 International Kidney Cancer Symposium (IKCS): Europe meeting focusing on later lines of systemic therapy in advanced kidney cancer, Drs. Camillo Porta and Laurence Albiges debated the approach to second-line therapy in metastatic renal cell carcinoma (mRCC). Dr. Porta presented first, emphasizing evidence-based second line treatment approaches.
Presented by Lisa Pickering, MD, PhD
In the fifth session of the 2022 International Kidney Cancer Symposium (IKCS): Europe meeting focusing on first-line systemic therapy in advanced kidney cancer (metastatic renal cell carcinoma, mRCC), Dr. Pickering presented the first side of a debate regarding treatment selection, defending the approach of immune checkpoint inhibition combined with tyrosine kinase inhibitor (IO/TKI).
Presented by Aristotelis Bamias, MD, PhD
In the fifth session of the 2022 International Kidney Cancer Symposium (IKCS): Europe meeting focusing on first-line systemic therapy in advanced kidney cancer, Dr. Aristotelis Bamias presented the second side of the debate regarding treatment selection, defending the approach of dual immune checkpoint inhibition with nivolumab and ipilimumab.
Presented by Bernard Escudier, MD,
The 2022 International Kidney Cancer Symposium (IKCS) European Annual meeting included an oral abstract session and presentation by Dr. Bernard Escudier discussing nivolumab + ipilimumab + cabozantinib for previously untreated advanced renal cell carcinoma (RCC), which was a discontinued study arm in the phase 3 CheckMate 9ER trial.
Presented by Sun Young Rha MD, PhD
In Poster Session C on the third day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 focused on Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers. In this session, Dr. Rha presented subgroup analyses of efficacy and safety from the CLEAR trial of Lenvatinib and pembrolizumab among East Asian patients with advanced renal cell carcinoma (aRCC).
Presented by David Cella, PhD
The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session highlighting work from Dr. David Cella and investigators presenting results assessing HRQoL in previously untreated patients with advanced renal cell carcinoma in the CheckMate 9ER trial. 
Presented by Axel Bex, MD, PhD
 In an oral abstract Dr. Axel Bex presented results of the NeoAvAx study examining neoadjuvant avelumab and axitinib following nephrectomy for patients who are at high risk for recurrence.
Presented by Toni K. Choueiri, MD
In an oral abstract Dr. Toni Choueiri presented 30-month follow-up from the KEYNOTE-564 trial of post-nephrectomy adjuvant pembrolizumab in patients with renal cell carcinoma (RCC).
Presented by Martin H Voss, MD
Dr. Martin Voss presented the PIVOT IO 011 study, a phase 1/2 study evaluating of bempegaldesleukin plus nivolumab and TKI versus nivolumab and TKI alone in patients with previously untreated advanced or metastatic RCC.
Presented by Toni K. Choueiri MD
Dr. Toni Choueiri presented the rationale and design of the TiNivo-2 trial, examining tivozanib with or without nivolumab in patients with renal cell carcinoma (RCC) who have progressed following one or two lines of therapy, one of which was an immune checkpoint inhibitor.
Presented by Neil Shah, MBBS
Dr. Neil Shah and colleagues presented results of a real-world assessment of changing treatment patterns and sequence for patients with metastatic renal cell carcinoma in the first-line setting. 
Presented by Robert Dreicer, MD, MS, MACP, FASCO
The SUO 2021 annual meeting in Orlando, FL hosted a second State of the Art Lecture by Dr. Robert Dreicer, MD, MS, MACP, FASCO discussing adjuvant therapy for kidney cancer.
Presented by Kevin Lu, MD
The SIU 2021 annual meeting included a master class on advanced kidney cancer with a presentation by Dr. Kevin Lu discussing nephrectomy as part of the sequencing options in metastatic renal cell carcinoma (RCC) with the primary in place.
Presented by Pedro C. Barata, MD, MSc

At the 2021 International Kidney Cancer Symposium (IKCS): North America meeting, Dr. Barata presented their work examining gene expression profiling (GEP) in non-clear cell renal cell carcinoma. They employed DNA/RNA next-generation sequencing of tumor samples from the Caris Life Sciences lab. They defined molecular subgroups according to the criteria set out by Motzer et al. and examined 7 clusters.

Presented by Bradley McGregor, MD
The International Kidney Cancer Symposium 2021 annual hybrid meeting included a non-clear cell renal cell carcinoma (RCC) session and a presentation by Dr. Bradley McGregor discussing recent and future studies of systemic therapy for non-clear cell RCC.
Presented by Toni K. Choueiri, MD
In a session of the 2021 International Kidney Cancer Symposium (IKCS): North America meeting focused on the role and effects of adjuvant immunotherapy in renal cell carcinoma (RCC) on subsequent first-line therapy, Dr. Choueiri provided an overview of his perspective of the future of adjuvant therapy in this disease space.
Presented by Toni K. Choueiri, MD
In this presentation, Dr. Toni Choueiri discussed patient-reported outcomes (PROs) from KEYNOTE-564, a randomized phase 3 study of adjuvant Pembrolizumab versus placebo in patients with renal cell carcinoma (RCC).
Presented by Naveen S. Vasudev, PhD, MRCP, MBChB, BMSc (Hons)
The ESMO 2021 annual meeting’s non-prostate cancer proffered paper session included a presentation by Dr. Naveen Vasudev discussing results of the phase II PRISM trial assessing nivolumab combination with alternatively scheduled ipilimumab in first-line treatment of advanced renal cell carcinoma (RCC).
Presented by Yann Vano, MD
The ESMO 2021 virtual annual meeting’s non-prostate cancer session included a presentation by Dr. Yann Vano discussing the CABIR study of patients receiving cabozantinib-nivolumab versus nivolumab-cabozantinib after receiving a prior VEGFR TKI for metastatic clear cell RCC. Nivolumab and cabozantinib are two approved agents after a prior TKI in metastatic RCC patients.
Presented by Brina Rini, MD
The ESMO 2021 annual meeting’s non-prostate cancer session included a presentation by Dr. Brian Rini discussing a new 3-arm phase 3 trial concept and design, which will randomize patients with advanced clear cell RCC in the first-line setting to either pembrolizumab + belzutifan + lenvatinib versus MK-1308A + lenvatinib versus pembrolizumab + lenvatinib.
Presented by Robert J. Motzer, MD
The ESMO 2021 virtual annual meeting’s non-prostate cancer session included a presentation by Dr. Robert Motzer discussing updated data from the CheckMate 214 trial with 5-years of follow-up.
Presented by Toni K. Choueiri, MD
The ESMO 2021 annual meeting’s non-prostate cancer session included a presentation by Dr. Toni Choueiri discussing outcomes of subgroup analyses and a toxicity update among patients in the phase 3 CLEAR trial for advanced renal cell carcinoma (RCC).
Presented by Toni K. Choueiri. MD
In this presentation, Dr. Toni Choueiri presented results from KEYNOTE-564, a study of adjuvant pembrolizumab administered for one year after complete surgical resection of clear cell RCC. The eligibility and study design are shown below. The primary endpoint was disease-free survival by investigator assessment. 
Presented by Rana R. McKay, MD
The much anticipated ASCO 2021 annual program plenary session included a discussant presentation by Dr. Rana McKay providing her expertise on the recently presented KEYNOTE 564 phase 3 trial with her talk entitled “A Quantum Leap in Cancer Adjuvant Immunotherapy”.
Presented by Ramaprasad Srinivasan, M.D., Ph.D

Building on the presentations from Dr. Linehan regarding the genetic causes of renal cell carcinoma (RCC) and from Dr. McDermott regarding current and future direction for immunotherapy in RCC, Dr. Srinivasan presented on challenges and emerging strategies for systemic therapy in kidney cancer.

Presented by David F. McDermott, MD
The European International Kidney Cancer Symposium 2021 virtual meeting’s keynote lecture was provided by Dr. David McDermott discussing kidney cancer as a model for a curable neoplasm. 
Presented by Yann-Alexandre Vano, MD
Dr. Vano discussed biomarker-driven trials. He first argued for the rationale of biomarker-driven trials based on the rationale that metastatic kidney cancer represents an incurable disease and current therapies have significant toxicity. He further emphasized that, based on drug development over the past two decades, there are many treatment options in mRCC that improve survival.
Presented by Thomas Powles, MBBS, MRCP, MD
The European International Kidney Cancer Symposium 2021 Virtual Meeting included a systemic therapy session and a presentation by Dr. Thomas Powles discussing tissue-based biomarkers for potential clinical adoption in renal cancer.
Presented by Camillo Porta, MD
To help guide treatment choices for those who progress on first-line therapy, Dr. Camillo Porta discussed modern therapeutic approaches in second-line and later therapies in a presentation at the European International Kidney Cancer 2021 Virtual Annual Meeting.
Presented by Stephanie A. Berg, DO
Following presentations by Dr. Robert Motzer discussing results of the CLEAR study of lenvatinib plus pembrolizumab or everolimus versus sunitinib in first-line treatment of advanced renal cell carcinoma and by Dr. Sumanta Pal looking at the SWOG 1500 trial of sunitinib, cabozantinib, crizotinib, and savolitinib in patients with metastatic papillary renal cell carcinoma.
Presented by Brian I. Rini, MD
The activity of tivozanib after axitinib has not been previously defined, and as such the activity of tivozanib after prior therapy types including axitinib is of clinical relevance. At the 2021 ASCO GU, Dr. Brian Rini and colleagues presented results of the TIVO-3 trial testing tivozanib in patients with advanced RCC who had progressed after prior axitinib treatment.
Presented by David Cella, PhD
The treatment landscape for first-line therapy among patients with metastatic renal cell carcinoma (mRCC) has changed dramatically over the past 2 years. In 2018, publication of the CheckMate214 data demonstrated a survival benefit for patients treated with nivolumab and ipilimumab compared with sunitinib in intermediate and poor-risk mRCC, ushering in the immunotherapy era for mRCC.
Presented by Andrea B. Apolo, MD
Cabozantinib, nivolumab, and ipilimumab have been increasingly utilized for a number of genitourinary malignancies, most prominently in renal cell carcinoma. In a dose-escalation study, combinations of cabozantinib and nivolumab (CaboNivo) and cabozantinib, nivolumab, and ipilimumab (CaboNivoIpi) demonstrated promising efficacy and safety in a dose-escalation phase I study.
Presented by Toni Choueiri, MD, MS
In this state-of-the-art presentation, Dr. Toni Choueiri gave an overview of the management of advanced kidney cancer. Several years ago, before the era of immunotherapy, when vascular endothelial growth factor (VEGF) receptor inhibitors were compared and used to treated advanced kidney cancer patients, the median overall survival was only 13 months.
Presented by Yann-Alexandre Vano, MD, PhD
Sunitinib was standard first line treatment for metastatic clear cell renal cell carcinoma (mccRCC) for many years until multiple clinical trials showed superior efficacy of various treatment combinations including nivolumab and ipilimumab in International Metastatic RCC Database Consortium (IMDC) intermediate or poor-risk disease.
Presented by Tim Q. Eisen, PhD, MB, BChir
Barcelona, Spain (UroToday.com) Four large, randomized Phase 3 clinical trials (S-TRAC, ASSURE, PROTECT, and ATLAS) evaluated adjuvant VEGF tyrosine kinase inhibitors in patients with resected renal cell carcinoma (RCC).
Presented by Axel Bex, MD, PhD
Barcelona, Spain (UroToday.com) The current standard for advanced localized renal cell carcinoma (RCC) is nephrectomy. Unfortunately, for better or worse, the series of adjuvant therapy
Presented by Marc-Oliver Grimm
Barcelona, Spain (UroToday.com) Dr. Marc-Oliver Grimm provided an overview of the many changes in the landscape for advanced renal cell carcinoma at the urogenital cancer treatment at a glance session. He started by highlight that the guidelines for advanced kidney cancer have been revamped recently
Presented by Cristina Suarez, MD
Munich, Germany (UroToday.com) IMmotion 150 (Phase II) compared the efficacy of atezolizumab (atezo) plus bevacizumab (bev) with atezolizumab alone and sunitinib alone
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