The hypoxia-inducible factor (HIF)-2α inhibitor belzutifan significantly reduced the risk of progression of clear cell renal cell carcinoma in patients previously treated with immune checkpoint inhibitors and antiangiogenic therapies compared with everolimus. The phase III LITESPARK-005 trial, led...
A secondary analysis from the phase III SWOG S0931 EVEREST trial found patients with clear cell renal cell carcinoma at very high risk of recurrence after nephrectomy who received adjuvant everolimus had a statistically significant improvement in recurrence-free survival compared to patients who...
Clear cell renal cell carcinoma is the most common type of kidney cancer, comprising 80% of all malignant tumors found within the kidney. Although some clear cell renal cell carcinoma tumors are sensitive to immune checkpoint inhibitors, currently, there are no measures to predict whether a tumor...
Older adults diagnosed with kidney tumors that are not suitable for surgery may benefit from targeted, high-dose radiation, a new study from Australian and Dutch researchers suggests. A multi-institutional phase II study—TransTasman Radiation Oncology Group (TROG) FASTRACK II—found 100% local...
The addition of the monoclonal antibody atezolizumab to the tyrosine kinase inhibitor cabozantinib failed to improve progression-free survival and overall survival vs cabozantinib alone in patients with advanced renal cell carcinoma (previously treated with an immune checkpoint inhibitor) in the...
In a phase II trial (KEYNOTE-B61) reported in The Lancet Oncology, Laurence Albiges, MD, PhD, of Gustave Roussy, Paris–Saclay University, Villejuif, France, and colleagues found that first-line pembrolizumab plus lenvatinib produced durable responses in patients with advanced non–clear cell renal...
A new report published by Knudsen et al in PLOS ONE focused on the clinical validation of a drug response predictor (DRP) biomarker algorithm for dovitinib, a receptor tyrosine kinase inhibitor of VEGFR1–3, PDGFR, FGFR1/3, c-KIT, FLT3, and topoisomerase 1 and 2. Data showed that the DRP-dovitinib...
The addition of cabozantinib to nivolumab plus ipilimumab prolonged progression-free survival in untreated intermediate-risk patients with advanced renal cell carcinoma (RCC), according to the first results of the phase III COSMIC-313 trial. These findings were presented as a Presidential Symposium ...
The 3-year follow-up of the phase III CheckMate 9ER trial demonstrates superior outcomes with the combination of nivolumab plus cabozantinib vs the former standard-of-care sunitinib as first-line treatment of advanced or metastatic renal cell carcinoma.1 These benefits were achieved with the...
At extended follow-up, lenvatinib plus pembrolizumab showed sustained superiority over sunitinib for overall and progression-free survival as first-line treatment for advanced renal cell carcinoma.1 The majority of the benefit was observed in intermediate- and poor-risk subgroups, according to the...
It is an exciting time in the development of new treatments for urologic cancers. There have been a number of major changes both in advanced disease and in the perioperative setting over the past year. Urothelial and Bladder Cancers In urothelial cancer, at last, we have randomized data supporting...
In the phase III EVEREST trial reported in The Lancet, Christopher W. Ryan, MD, and colleagues found that adjuvant everolimus was not associated with a significant improvement in event-free survival vs placebo in patients at high risk of disease recurrence following surgery for renal cell...
In the phase II KEYNOTE-B61 trial reported in The Lancet Oncology, Laurence Albiges, MD, PhD, and colleagues found that first-line pembrolizumab plus lenvatinib produced durable responses in patients with advanced non–clear cell renal cell carcinoma. As stated by the investigators,...
In the phase III CONTACT-03 trial reported in The Lancet, Sumanta Pal, MD, FASCO, and colleagues found that the addition of atezolizumab to cabozantinib did not improve outcomes in patients with renal cell carcinoma whose disease progressed on or after prior immune checkpoint inhibitor treatment....
This is Part 3 of Treatment Considerations in Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Brian Rini, Pedro Barata, and Kathryn Beckermann discuss the treatment of immunotherapy (IO)-refractory advanced renal cell carcinoma (RCC). The patient is a 65-year-old female who has been on axitinib plus pembrolizumab for the past 4 years. She originally presented with pulmonary and lymph node metastases 9 months after nephrectomy for a T3a clear cell RCC. She obtained a partial response after six cycles and tolerated treatment well, but imaging now shows new liver, pulmonary, and mediastinal lesions. The faculty discuss next steps for this patient, whether there is any benefit to sequential PD(L)-1 blockade in RCC, and the results of the recent phase III CONTACT-03 trial.
This is Part 2 of Treatment Considerations in Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Brian Rini, Pedro Barata, and Kathryn Beckermann discuss the front-line treatment of advanced renal cell carcinoma (RCC). The patient is a 63-year-old male who presents with multifocal, biopsy-proven pulmonary metastases 4 years after nephrectomy for locally advanced clear cell RCC. He is classified as IMDC favorable risk, is asymptomatic, and has normal labs. At 12 months observation, he receives stereotactic body radiotherapy for one pulmonary nodule. He develops mild back pain, and routine imaging reveals a hypervascular paraspinal metastasis, which is diagnosed as clear cell RCC. The faculty discuss what the optimal treatment plan would be for patient such as this, as well as the multitude of first-line immunotherapy combinations currently available in the first-line setting.
This is Part 1 of Treatment Considerations in Renal Cell Carcinoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Brian Rini, Pedro Barata, and Kathryn Beckermann discuss the role of adjuvant therapy for renal cell carcinoma (RCC). The patient is a 68-year-old African American female who presents with left flank pain and hematuria. CT scan reveals a large left renal mass with right ventricular thrombus and no distant metastases. After undergoing left radical nephrectomy, she is diagnosed with clear cell RCC, 10.7 cm, grade 3, pT3aN0, with no sarcomatoid changes or necrosis. The faculty discuss the importance of estimating risk of recurrence to determine the absolute benefit of adjuvant therapy, as well as whether immunotherapy has a role in the adjuvant treatment of RCC.
In an analysis of National Wilms Tumor Study (NWTS) protocols reported in the Journal of Clinical Oncology, Oosterom et al identified the incidence of treatment-related severe hepatopathy in patients with Wilms tumor and described outcomes in these patients. Study Details The study involved data...
At extended follow-up, lenvatinib plus pembrolizumab showed sustained superiority over sunitinib for overall and progression-free survival as first-line treatment for advanced renal cell carcinoma.1 The majority of the benefit was observed in intermediate- and poor-risk subgroups, according to the...
The positron-emission tomography (PET) tracer zirconium (Zr)-89–DFO-girentuximab may accurately identify patients with clear cell renal cell carcinoma and differentiate the disease from other types of renal tumors, according to findings presented by Calais et al at the Society of Nuclear Medicine...
Rana R. McKay, MD, of the University of California, San Diego, and Brian I. Rini, MD, of Vanderbilt-Ingram Cancer Center, discuss the 5-year follow-up results with the combination of a checkpoint inhibitor plus a VEGFR tyrosine kinase inhibitor as first-line treatment for patients with advanced clear cell renal cell carcinoma (RCC). Pembrolizumab plus axitinib continued to demonstrate improved survival outcomes as well as overall response rate vs sunitinib for patients with previously untreated disease (Abstract LBA4501).
Rana R. McKay, MD, of the University of California, San Diego, and Toni K. Choueiri, MD, of Dana-Farber Cancer Institute and Harvard Medical School, discuss results from the phase III CONTACT-03 study, showing that, for patients with metastatic renal cell carcinoma (RCC), adding the PD-L1 inhibitor atezolizumab to cabozantinib did not improve clinical outcomes compared with treatment with cabozantinib alone. In addition, higher toxicities were observed in the combination arm (Abstract LBA4500).
Thomas E. Hutson, DO, PharmD, of Texas Oncology, discusses the 4-year follow-up results from the CLEAR study for patients with advanced renal cell carcinoma (RCC). The data showed that lenvatinib plus pembrolizumab continues to demonstrate clinically meaningful benefit vs sunitinib in overall and progression-free survival, as well as in overall and complete response rates, in first-line treatment (Abstract 4502).
In a meta-analysis reported in a research letter in JAMA Network Open, Maiorano et al found that first-line anti–PD-L1 treatment combinations did not significantly improve overall survival vs sunitinib in patients with metastatic renal cell carcinoma. A progression-free survival benefit was...
The targeted kinase inhibitor cabozantinib plus a two-drug immunotherapy combination of nivolumab and ipilimumab may be capable of slowing cancer progression in patients with advanced renal cell carcinoma who received no prior lines of therapy, according to a study published by Choueiri et al in...
Researchers may have shed light on how radiation therapy impacts immune cells and tumor cells in renal cell carcinoma, according to a novel study published by Chow et al in the Journal for ImmunoTherapy of Cancer. The new findings may provide key information for planning treatment regimens that...
Researchers have created the largest single-cell atlas of renal cell carcinoma brain metastases, with matched primary and extracranial metastases, which has potentially enabled them to discover key biological mechanisms contributing to an immunosuppressive tumor microenvironment in the brain...
Treatment with the allogeneic chimeric antigen receptor (CAR) T-cell therapy ALLO-316 resulted in encouraging response rates and disease control rates for patients with metastatic clear cell renal cell carcinoma who did not respond to prior therapy, according to new findings presented by Srour et...
In a U.S. phase II trial reported in The Lancet Oncology, Toni K. Choueiri, MD, and colleagues found that the combination of the hypoxia-inducible factor 2α inhibitor belzutifan and the VEGFR kinase inhibitor cabozantinib showed promising activity in patients with advanced clear cell renal cell...
Researchers have revealed that the number of tumor-infiltrating lymphocytes, the state of necrosis, and mutations to the tumor-suppressor gene PBRM1 form a biomarker signature that may predict how patients with renal cell carcinoma will respond to immunotherapy, according to a novel study published ...
In a Russian single-institution prospective cohort study reported in the Journal of Clinical Oncology, Sheikh et al found that quitting smoking after a diagnosis of renal cell carcinoma (RCC) was associated with improved disease progression and survival outcomes among patients. Study Details The...
Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, and Christopher Sweeney, MBBS, of Dana-Farber Cancer Institute, discuss two important phase III studies on renal cell cancer (RCC) presented at ESMO 2022: IMmotion010, which examined the efficacy and safety of atezolizumab vs placebo as adjuvant therapy in patients with RCC at increased risk of recurrence after nephrectomy; and CheckMate 914, which compared nivolumab monotherapy or nivolumab combined with ipilimumab vs placebo in patients with localized disease who underwent radical or partial nephrectomy and who are at high risk of relapse. (Abstract LBA4 & LBA66).
The 3-year follow-up of the phase III CheckMate 9ER trial demonstrates superior outcomes with the combination of nivolumab plus cabozantinib vs the former standard-of-care sunitinib as first-line treatment of advanced or metastatic renal cell carcinoma.1 These benefits were achieved with the...
As reported in The Lancet Oncology by Toni K. Choueiri, MD, and colleagues, extended follow-up of the phase III CLEAR trial has shown maintained progression-free and overall survival benefits with first-line lenvatinib plus pembrolizumab vs sunitinib in patients with advanced clear cell renal cell...
In the phase II CALYPSO study reported in the Journal of Clinical Oncology, Suárez et al found that the combination of the MET inhibitor savolitinib and the PD-L1 inhibitor durvalumab did not reach the confirmed response rate endpoint in patients with metastatic papillary renal cancer but showed...
Sumanta K. Pal, MD, introduces his City of Hope colleagues, Hedyeh Ebrahimi, MD, MPH, who discusses the prevalence of dietary modification and supplement use in patients with metastatic renal cell carcinoma, and Daniela Castro, MSc, who discusses expanding eligibility criteria in kidney, prostate, and urothelial cancer trials to more accurately reflect the real-world population and reducing exclusion criteria. (Abstract 662, 612, 34, 453)
Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discusses interim results from the CaboPoint study, which evaluated cabozantinib as second-line treatment in patients with unresectable, locally advanced or metastatic renal cell carcinoma with a clear cell component. Disease in the study participants had progressed after prior treatment with ipilimumab and nivolumab in combination or combined with VEGF-targeted therapy. (Abstract 606).
Michael B. Atkins, MD, of Georgetown Lombardi Comprehensive Cancer Center, discusses treatment-free survival outcomes from the HCRN GU16-260-Cohort A study of patients with previously untreated advanced clear cell renal cell carcinoma who received nivolumab and salvage nivolumab plus ipilimumab. The regimen appears to result in substantial treatment-free survival with few treatment-related adverse events. (Abstract 604).
As reported in The Lancet by Robert J. Motzer, MD, and colleagues, part A of the phase III CheckMate 914 trial has shown no improvement in disease-free survival with adjuvant nivolumab/ipilimumab vs placebo in resected localized clear cell renal cell carcinoma. Part B of the trial is evaluating...
Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, discusses new data from the COSMIC-313 study of patients with advanced renal cell carcinoma of IMDC (International Metastatic RCC Database Consortium) intermediate or poor risk. Those who received cabozantinib instead of placebo with nivolumab and ipilimumab as first-line treatment seemed to experience improved progression-free survival. A subgroup analysis suggested the benefit was primarily in patients with an intermediate risk. Follow-up for overall survival is ongoing. (Abstract 605).
As reported in The Lancet Oncology by Brown et al, the phase II/III STAR trial showed that noninferiority in overall survival and quality-adjusted life-years (QALYs) could not be concluded for temporary treatment cessation vs continuous treatment with first-line tyrosine kinase inhibitor therapy in ...
Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, discusses a biomarker analysis from the phase III CheckMate 9ER trial of nivolumab plus cabozantinib vs sunitinib for the treatment of patients with advanced renal cell carcinoma. The ongoing study aims to identify a predictive biomarker that may potentially guide therapeutic choices. (Abstract 608).
In an analysis from the Childhood Cancer Survivor Study (CCSS) reported in the Journal of Clinical Oncology, Weil et al found that survivors of unilateral Wilms tumor were at an increased risk for severe chronic health conditions. Study Details The study involved 2,008 5-year survivors diagnosed...
New findings revealed that the highest mortality rates for prostate cancer among White male patients were found in the Western United States—including California—despite low incidence rates, according to a new study published by Schafer et al in European Urology. However, when compared with White...
Sumanta Pal, MD, of the City of Hope Comprehensive Cancer Center, discusses phase I results from the COBALT-RCC study, a first-in-human clinical trial exploring CD70 CAR T-cell therapy in patients with clear cell renal cell carcinoma. The agent appeared to show an excellent safety profile with no unexpected toxicities and antitumor activity. One durable complete response is the first to be achieved with allogeneic CAR T-cell therapy in patients with relapsed or refractory solid tumors, offering proof of concept for further exploration of CD70-targeted CAR T cells in renal cell and other CD70-positive malignancies (Abstract 558).
In an individual patient meta-analysis reported in The Lancet Oncology, Shankar Siva, PhD, and colleagues found that patients receiving stereotactic ablative body radiotherapy (SABR) for primary localized renal cell carcinoma had long-term outcomes indicating that the treatment is safe and...
In a Dutch single-institution retrospective cohort study reported in JACC: CardioOncology, Kaptein et al identified the prevalence of venous tumor thrombus at diagnosis in patients with renal cell carcinoma (RCC) and the associated risk of venous thromboembolism. Study Details The study included...
Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, discusses phase III results of the CheckMate 914 trial, which explored the efficacy of adjuvant nivolumab plus ipilimumab vs placebo in the treatment of patients with localized renal cell carcinoma who are at high risk of relapse after nephrectomy (Abstract LBA4).
Three negative phase III trials presented at the European Society for Medical Oncology (ESMO) Congress 2022 may dampen enthusiasm for immunotherapy as adjuvant therapy for renal cell carcinoma (RCC). None of the three trials—CheckMate 914, IMmotion010, and PROSPER—met its primary endpoint.1-3 The...
The addition of cabozantinib to nivolumab plus ipilimumab prolonged progression-free survival in untreated intermediate-risk patients with advanced renal cell carcinoma (RCC), according to the first results of the phase III COSMIC-313 trial. These findings were presented as a Presidential Symposium ...