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This is Part 3 of New Approaches to Treatment Sequencing in Advanced Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Daniel George, Michael Harrison, and Catherine Fahey discuss the treatment of recurrent chromophobe renal cell carcinoma (RCC). The patient is a 67-year-old man who presented with flank pain in 2017 and is found to have a right renal mass on CT. Pathology following nephrectomy reveals a 19-cm chromophobe pathologic stage IIIa RCC, grade 2, with no involved nodes or metastases. He is followed until 2020, when CT reveals an 8.8-cm retroperitoneal mass, which CT-guided biopsy confirms to be a recurrence of his chromophobe RCC. The next month, an exploratory laparotomy reveals multiple liver metastases. In the conversation that follows, the faculty discuss possible treatment options for this patient with non–clear cell RCC, how to approach oligoprogressive disease, and whether immunotherapy may play a role in the treatment of chromophobe RCC.
This is Part 2 of New Approaches to Treatment Sequencing in Advanced Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Daniel George, Michael Harrison, and Catherine Fahey discuss the treatment of recurrent renal cell carcinoma (RCC). The patient is a 51-year-old man who was originally diagnosed in 2013 with stage III clear cell RCC, grade 2. He underwent nephrectomy and was disease-free for 5 years until 2018, when a CT scan showed a 1.1-cm right adrenal nodule and multiple enlarging lung nodules. Video-assisted thoracic surgery revealed clear cell RCC. In the conversation that follows, the faculty discuss the treatment course for this patient as his disease continues to slowly progress, when to offer tumor-directed therapy vs systemic therapy, later-line treatment options, and the importance of prioritizing patient quality of life.
This is Part 1 of New Approaches to Treatment Sequencing in Advanced Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Daniel George, Michael Harrison, and Catherine Fahey discuss the treatment of a patient with metastatic renal cell carcinoma (RCC) and multiple adverse risk factors. The patient is a 67-year-old woman who presented to her primary care provider (PCP) with 20-pound weight loss, anemia, low appetite, and new-onset hypertension. In addition to anemia, she is found to have leukocytosis, neutrophilia, thrombocytosis, and hypercalcemia. One month later, she presents to her PCP with severe headache and is noted to have hepatomegaly. A CT scan of the abdomen and pelvis reveals a right renal mass with possible invasion of the liver. In the conversation that follows, the faculty discuss the impact of this patient’s risk factors on her choice of treatment, whether immunotherapy could be considered, the importance of goals-of-care conversations, and more.
In extended follow-up of the phase II LITESPARK-004 trial reported in The Lancet Oncology, Srinivasan et al found that use of the hypoxia-inducible factor-2α inhibitor belzutifan was associated with maintained benefit in patients with von Hippel–Lindau disease–associated renal cell carcinoma. The...
The U.S. Food and Drug Administration (FDA) has approved bevacizumab-nwgd (Jobevne), a biosimilar to bevacizumab (Avastin), for intravenous use. Bevacizumab-nwgd is a recombinant humanized monoclonal antibody and a vascular endothelial growth factor (VEGF) inhibitor that binds with VEGF and blocks...
In a health-related quality-of-life (QOL) analysis reported in The Lancet Oncology, Powles et al found that belzutifan had better QOL on patient-reported outcomes vs everolimus in patients with advanced renal cell carcinoma in the phase III LITESPARK-005 trial. Study Details Belzutifan is approved...
Weight patterns throughout life may affect an individual’s likelihood of developing renal cell carcinoma, according to a recent study published by Deng et al in Cancer. Study Methods and Results In the study, investigators used data from the NIH-AARP Diet and Health Study to assess weight patterns...
A simple urine test could accurately detect clear cell renal cell carcinoma (RCC) recurrence at an early stage, potentially sparing patients from undergoing invasive scans and enabling quicker access to treatment, according to new findings presented by Dabestani et al at the European Association of ...
The PD-1 inhibitor nivolumab plus the tyrosine kinase inhibitor cabozantinib continues to demonstrate a significant survival advantage over sunitinib alone in patients with previously untreated advanced renal cell carcinoma, according to data presented at the 2025 ASCO Genitourinary Cancers...
Ceasing or pausing a combination of the immune checkpoint inhibitor nivolumab and the oral tyrosine kinase inhibitor (TKI) axitinib after 2 years may be safe among patients with metastatic renal cell carcinoma who achieved a positive response to this treatment, according to updated analysis of a...
Patients with stage III or IV clear cell renal cell carcinoma may have achieved a successful anticancer immune response following initiation of a novel personalized cancer vaccine, according to a recent study published by Braun et al in Nature. Background The standard treatment for stage III or IV...
In a phase II trial (LITESPARK-003), reported in The Lancet Oncology, Choueiri et al found that the combination of belzutifan—a first-in-class HIF-2α inhibitor—and cabozantinib showed promising activity in the first-line treatment of patients with advanced clear cell renal cell carcinoma. Study...
Researchers have found a possible source of the variability in patterns of clear cell renal cell carcinoma (RCC), the most common kidney cancer diagnosed in adults. Katherine Alexander, PhD, Assistant Professor at Cold Spring Harbor Laboratory, and Shelley Berger, PhD, Professor at the University...
In addition to our in-depth analysis of important clinical trials presented at the European Society for Medical Oncology (ESMO) Congress 2024, there is always room for more coverage from The ASCO Post, including these brief summaries of other presentations of interest. They focus on a potential...
The studies summarized below were reported online over the past month in The ASCO Post, generating a high number of visitors. For comprehensive news of these studies and more, visit ASCOPost.com. Triple-Negative Breast Cancer: Phase III KEYNOTE-522 The phase III KEYNOTE-522 trial has...
As reported in the Journal of Clinical Oncology by Motzer et al, part B of the phase III CheckMate 914 trial showed no disease-free survival benefit with the adjuvant use of nivolumab vs placebo in patients with localized renal cell carcinoma at high risk of recurrence after nephrectomy. These...
As reported in The Lancet by Choueiri et al, the phase III TiNivo-2 trial has shown that immune checkpoint inhibitor rechallenge with nivolumab plus tivozanib did not improve progression-free survival vs tivozanib alone in patients with metastatic renal cell carcinoma following immune checkpoint...
In a phase III trial reported in The Lancet Oncology, Shuch et al found that zirconium Zr-89–labeled girentuximab (Zr-89 girentuximab) positron-emission tomography/computed tomography (PET-CT) imaging was accurate in detecting clear cell renal cell carcinoma (RCC) in patients with renal masses....
As reported in the Journal of Clinical Oncology by Barata et al, the final overall survival results of the phase II SWOG 1500 trial indicated no significant benefit with cabozantinib vs sunitinib in patients with advanced papillary renal cell carcinoma. Study Details In the open-label multicenter...
As reported in The New England Journal of Medicine by Choueiri and colleagues, the phase III LITESPARK-005 trial has shown improved progression-free survival with the hypoxia-inducible factor–2α inhibitor belzutifan vs everolimus in previously treated patients with advanced clear-cell renal cell...
In a subgroup analysis of the EVEREST trial reported in JAMA Network Open, Gulati et al found that adjuvant everolimus did not improve recurrence-free survival vs placebo in patients with localized papillary or chromophobe non–clear cell renal cell carcinoma (RCC). Study Details In the trial,...
As reported in the Journal of Clinical Oncology by Andrea B. Apolo, MD, and colleagues, findings in expansion cohorts of a phase I study showed the activity of cabozantinib/nivolumab alone or with the addition of ipilimumab in patients with advanced/metastatic genitourinary (GU) tumors. Study...
As reported in The Lancet Oncology by Allaf et al, a planned interim analysis of the phase III PROSPER ECOG-ACRIN EA8143 trial showed no recurrence-free survival benefit with perioperative nivolumab vs observation in patients undergoing nephrectomy for high-risk renal cell carcinoma. Study ...
Researchers have discovered a biomarker that could help identify which patients with clear cell renal cell carcinoma may be at greater risk of cancer recurrence, according to a recent study published by Mehra et al in JCO Precision Oncology. Background Approximately 3% to 5% of all cancer diagnoses ...
As reported in the Journal of Clinical Oncology by Nizar M. Tannir, MD, FACP, and colleagues, the phase III PIVOT-09 trial has shown no objective response or overall survival benefit with bempegaldesleukin plus nivolumab vs tyrosine kinase inhibitor (TKI) treatment with sunitinib or cabozantinib in ...
Laurence Albiges, MD, PhD, of Gustave Roussy, Université Paris-Saclay, discusses phase III findings showing that high baseline serum KIM-1 levels were associated with poorer prognosis but improved clinical outcomes with atezolizumab vs placebo in patients with renal cell carcinoma at increased risk of recurrence after resection. Increased post-treatment KIM-1 levels were found to be associated with worse disease-free survival (Abstract 4506).
Brian I. Rini, MD, of Vanderbilt Ingram Cancer Center, discusses phase III findings of the KEYNOTE-426 study of pembrolizumab plus axitinib vs sunitinib for patients with advanced renal cell carcinoma. He details the exploratory biomarker results, including RNA sequencing, whole-exome sequencing, and PD-L1 (Abstract 4505).
Toni K. Choueiri, MD, FASCO, of the Dana-Farber Cancer Institute, discusses phase III findings showing that, in patients with advanced renal cell carcinoma (RCC), the benefit of lenvatinib plus pembrolizumab vs sunitinib in overall response rate does not appear to be affected by such factors as gene‐expression signatures for tumor‐induced proliferation, PD‐L1 status, or the mutation status of RCC driver genes.
As reported in The New England Journal of Medicine by Toni K. Choueiri, MD, FASCO, of Dana-Farber Cancer Institute and Harvard Medical School, and colleagues, the third prespecified interim analysis of overall survival in the phase III KEYNOTE-564 trial has shown significant benefit with adjuvant...
Evidence from a small early trial called COBALT-RCC provides proof of concept for use of an allogeneic off-the-shelf CD70-targeted chimeric antigen receptor (CAR) T-cell therapy called CTX130 in patients with advanced clear cell renal cell carcinoma (RCC). CTX130 is engineered using gene-editing...
In a study reported in the Journal of Clinical Oncology, Xu et al found that higher levels of preoperative plasma kidney injury molecule-1 (pKIM-1) distinguished renal cell carcinoma from benign renal masses. As stated by the investigators, “Both clear cell and papillary renal cell carcinoma...
On December 14, 2023, the hypoxia-inducible factor inhibitor belzutifan (Welireg) was approved for patients with unresectable locally advanced or metastatic clear cell renal cell carcinoma with disease progression on previous treatment with a PD-1 or PD-L1 inhibitor and a vascular endothelial...
The novel investigational positron-emission tomography (PET) imaging agent gallium (Ga)-68–DPI-4452 may offer rapid and accurate visualization of lesions in patients with clear cell renal cell carcinoma, according to a recent study published by Hofman et al in The Journal of Nuclear Medicine. The...
Researchers have identified novel biomarkers in renal cell carcinoma subtypes, according to a new study published by Li et al in Cell Reports Medicine. The findings may help identify therapeutic targets in non–clear cell renal cell carcinomas. Background Renal cell carcinoma is a diverse cancer...
As reported in The New England Journal of Medicine by Toni K. Choueiri, MD, FASCO, and colleagues, the third prespecified interim analysis of overall survival in the phase III KEYNOTE-564 trial has shown a significant benefit with adjuvant pembrolizumab vs placebo in patients with clear cell renal...
This is Part 3 of Later-Line Considerations in Relapsed/Refractory Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Rana McKay, Bradley McGregor, and Sumanta K. Pal discuss the management of metastatic renal cell carcinoma (RCC) after disease progression on VEGF-targeted therapy and immunotherapy (IO). The patient is a 56-year-old woman who presented in 2015 with sharp abdominal pain. Imaging revealed a large renal mass, and CT of the chest and brain MRI were negative. She underwent a left nephrectomy, which revealed a 10.9-cm grade 3 renal cell carcinoma with renal vein invasion. After 4 years of surveillance, a CT of the chest, abdomen, and pelvis revealed pulmonary nodules and a right adrenal nodule. She started treatment with nivolumab plus ipilimumab, continuing to receive maintenance nivolumab after completion of therapy. One year later, she developed a retinal detachment related to immune infiltrates, which led to the permanent discontinuation of nivolumab. She continued to be monitored, and her disease was found to be stable with the exception of growing right adrenal nodule, for which she received stereotactic ablative body radiotherapy. The following year, she experienced disease progression in her lungs with multiple new pulmonary nodules. In the conversation that follows, the faculty discuss how to approach the management of a patient presenting with newly diagnosed metastatic RCC, the role of radiation therapy for patients with oligoprogressive disease, and treatment options in the later-line setting for patients whose disease progresses on VEGF-targeted therapy and IO.
This is Part 2 of Later-Line Considerations in Relapsed/Refractory Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Rana McKay, Bradley McGregor, and Sumanta K. Pal discuss the management of refractory renal cell carcinoma (RCC) after disease progression on adjuvant immunotherapy (IO). The patient is a 50-year-old man who underwent an early cancer detection test in 2022 and received a positive test result. A CT of the chest, abdomen, and pelvis revealed a 5.1-cm right upper pole mass in the kidney. He underwent a right partial nephrectomy and was found to have grade 3 clear cell RCC with perinephric fat invasion and renal vein invasion. The patient received pembrolizumab for 1 year, followed by a 3-month surveillance schedule. On his first subsequent scan, he was found to have new small pulmonary nodules and underwent a video-assisted thoracoscopic surgery, which confirmed clear cell RCC. In the conversation that follows, the faculty discuss their preferred methods of risk stratification, how to address small changes revealed on surveillance scans after IO therapy, and whether IO or VEGF-targeted therapy would be appropriate following disease progression on adjuvant IO.
This is Part 1 of Later-Line Considerations in Relapsed/Refractory Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Rana McKay, Bradley McGregor, and Sumanta K. Pal discuss the management of metastatic favorable-risk renal cell carcinoma (RCC) in a patient whose disease has progressed after receiving treatment with VEGF inhibitors and immunotherapy (IO). The patient is a 67-year-old woman who was diagnosed with localized clear cell RCC in 2007 and monitored with active surveillance. Almost 10 years after her original diagnosis, she developed progressive disease with a stable pulmonary nodule, a small but growing adrenal nodule, and a new pancreatic mass. Over the next 2 years, she received pazopanib, which was discontinued due to intolerance, and nivolumab, which was discontinued after growth of her adrenal nodules and pancreatic metastasis. In the conversation that follows, the faculty discuss when active surveillance may be appropriate for patients with renal cell carcinoma, how to approach patients who present with metastatic disease after a long latency period, the impact that sites of metastasis have on treatment options, and what options are available after disease progression on multiple lines of therapy.
The CD70-targeted allogeneic chimeric antigen receptor (CAR) T-cell therapy CTX130 may be effective in patients with advanced clear cell renal cell carcinoma, according to findings presented by Srour et al at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract CT002)...
As reported in the Journal of Clinical Oncology by Leonard J. Appleman, MD, PhD, and colleagues, the phase II ECOG-ACRIN E2810 trial showed no significant improvement in disease-free survival with pazopanib vs placebo in patients with metastatic renal cell carcinoma with no evidence of disease...
On December 14, 2023, the hypoxia-inducible factor inhibitor belzutifan (Welireg) was approved for patients with unresectable locally advanced or metastatic clear cell renal cell carcinoma with disease progression on previous treatment with a PD-1 or PD-L1 inhibitor and a vascular endothelial...
In a phase II study (FASTRACK II) reported in The Lancet Oncology, Shankar Siva, MBBS, PhD, and colleagues found that stereotactic ablative body radiotherapy (SABR) was effective in patients with primary kidney cancer who did not undergo resection. Study Details Seventy patients were enrolled in...
Invited discussant of KEYNOTE-564, Pedro Barata, MD, MSc, FACP, of the University Hospital Seidman Cancer Center, Cleveland, said the reasons for the disparate results in these two adjuvant trials of checkpoint inhibitors were likely the result of many factors. “Factors such as histology, different ...
In the third prespecified interim analysis of the phase III KEYNOTE-564 trial,1 adjuvant treatment with the PD-1 inhibitor pembrolizumab significantly improved overall survival compared with placebo in patients with intermediate- or high-risk clear cell renal cell carcinoma (RCC). However, a...
Invited discussant Lisa Pickering, PhD, FRCP, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, London, considered belzutifan to be a major advance in renal cell carcinoma (RCC). “LITESPARK-005 met both its primary endpoints of progression-free survival and overall response...
Belzutifan is a first-in-class, oral hypoxia-inducible factor (HIF)-2α inhibitor, and active HIF-2α is a key oncogenic driver in clear cell renal cancer. The manufacturer has filed a new drug application for the treatment of adults with RCC who experienced disease progression after PD-1/PD-L1– and...
Investigators may have found a significant unmet need for improved analyses and reporting of patient-reported outcomes in genitourinary cancer clinical trials, according to a recent study published by Paravathaneni et al in eClinicalMedicine. Background Genitourinary cancers affect over 444,000...
Thomas Powles, MD, of Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, and Queen Mary University of London, discusses overall survival results from the phase III KEYNOTE-564 study of adjuvant pembrolizumab vs placebo in patients with clear cell renal cell carcinoma (Abstract LBA359).
Andrew Johns, MD, of The University of Texas MD Anderson Cancer Center, discusses efficacy, safety, and tolerability data on tivozanib. The agent yielded a modest clinical benefit in a minority of patients with advanced clear cell renal cell carcinoma who received prior immune checkpoint–based therapies, cabozantinib, and lenvatinib with or without everolimus (Abstract 419).
Saby George, MD, of Roswell Park Comprehensive Cancer Center, discusses pharmacokinetics, efficacy, and safety results from CheckMate 67T, a phase III trial comparing the use of subcutaneous vs intravenous nivolumab in patients with advanced or metastatic clear cell renal cell carcinoma who have received prior systemic therapy (Abstract LBA360).