Nivolumab: 5 Years Since FDA Approval of the First Checkpoint Inhibitor for Renal Cell Carcinoma
Abstract
On November 23, 2015, the US Food and Drug Administration (FDA) approved nivolumab for the treatment of metastatic renal cell carcinoma (RCC), thus opening a new era of immunotherapy for this tumor. This review summarizes the 5-year experience of studying and using nivolumab in RCC patients.
Twitter as a Tool to Spread Communication Regarding Genitourinary Cancers During the COVID-19 Pandemic
Abstract
OBJECTIVES:
To better characterize the relay of information about prostate, kidney, and bladder cancer on Twitter in relation to the COVID-19 pandemic.
MATERIALS AND METHODS:
Tweets containing the joint hashtags “#COVID-19” and either “#bladder cancer”, “#kidney cancer”, or “#prostate cancer” were identified on the Twitter platform from January 1, 2020 to July 30, 2020. The Twitter handle responsible for each tweet was categorized as an Academic, Medical Education, Patient Advocacy Groups/Non-Profits, Pharmaceutical, or Other entity based on content domain. Descriptive statistics were used to summarize data on Twitter handle characteristics stratified by disease category (bladder, kidney, and prostate). Median/interquartile range and percentages were used to summarize continuous and categorical data, respectively. Number of tweets containing the relevant joint hashtags were tracked over time in relation to the cumulative United States case count of COVID-19.
RESULTS:
The content of 730 total tweets containing the joint hashtags “COVID-19” and either “#bladder cancer” (138 tweets), “#kidney cancer” (137 tweets), or “#prostate cancer” (455 tweets) from January 1, 2020 to July 31, 2020 were analyzed. We identified 326 unique Twitter handles across all disease states (62 bladder, 47 kidney, and 217 prostate-related). Academic Twitter handles accounted for the greatest number of tweets containing the joint hashtags (31%). Temporal tracking of tweets with regard to monthly U.S. COVID cases revealed that communication surged in March of 2020 and peaked in April for both bladder and kidney cancer, whereas related prostate cancer Twitter communication peaked in May of 2020.
CONCLUSIONS:
As COVID-19 case counts rose in the United States initially, so too did communication surrounding COVID-19 and genitourinary cancers on Twitter. Many of these conversations were driven by academically-associated Twitter accounts.
PBRM1 Mutations as a Predictive Biomarker for Immunotherapy in Metastatic Renal Cell Carcinoma: A Systematic Review
Abstract
INTRODUCTION:
Genomic features linked to prediction of response to immunotherapy in metastatic renal cell carcinoma (mRCC) are still lacking. Protein polybromo-1 (PBRM1) mutations have been studied as a potential biomarker of clinical benefit, with conflicting published data so far.
MATERIAL AND METHODS:
This systematic review was guided by the standards of the PRISMA statement to identify studies involving mRCC, immunotherapy and mutations in PBRM1. The main objective was to assess the relationship between PBRM1 mutations and response to immune checkpoint inhibitors (ICI) in patients with mRCC.
RESULTS:
After an initial search that identified 422 studies, 8 studies met the eligibility criteria and were selected for the final analysis. Data are included from 2 trials in the first-line treatment setting, and 6 trials in second- or later treatment lines evaluating the relationship between the presence of PBRM1 mutations and clinical benefit (CB) with ICI treatment. Regarding the first-line treatment setting, the analysis of both studies failed to show any CB in patients with PBRM1 mutations treated with ICI. However, for the second- and later treatment lines, the results were mixed.
CONCLUSIONS:
PBRM1 mutations may be a potential genomic biomarker to predict response to ICI treatment in patients with mRCC, mainly in second- and later treatment lines, but the existence of conflicting data in the literature highlights an important bias in the studies and the need for additional clinical validation in large, prospective trials.
Impact of SARS-CoV-2 Pandemic on Kidney Cancer Management
Abstract
BACKGROUND:
The SARS-CoV-2 pandemic still has a huge impact on the management of many chronic diseases such as cancer. Few data are presently available reagarding how the management of renal cell carcinoma (RCC) has changed due to this unprecedented situation.
OBJECTIVE:
To discuss the challenges and issues of the diagnosis and treatment of RCC in the COVID-19 era, and to provide recommendations based on the collected literature and our personal experience.
METHODS:
Systematic review of the available Literature regarding the management of RCC during the SARS-CoV-2 pandemic.
RESULTS:
Our review showed a prevalence of narrative publications, raising the issue of the real relevance of the evidence retrieved. Indeed, the only original data about RCC and COVID-19 found were a small retrospective case series and two surveys, providing either patients’ or physicians’ viewpoints.
CONCLUSIONS:
The expected delayed diagnosis of RCC could lead to an increase of advanced/metastatic cases; thus, proper therapeutic choices for patients with small renal masses should be carefully evaluated case by case, in order to avoid negative effects on long-term survival rates. The controversial interaction between immune checkpoint blockade and COVID-19 pathogenesis is more hypothetical than evidence-based, and thus immunotherapy should not be denied, whenever appropriate. To avoid treatments which won’t have an impact on patients’ survival, a honest and accurate evaluation of the cost/benefit ratio of each treatment option should be always performed. Finally, SARS-CoV-2 swab positivity should not prevent the continuation of ongoing active treatments in asymptomatic cases, or or after symptoms’ resolution.
Renal Cancer Without Primary Cancer in the Kidney: Extra-Renal TFE3 Translocation Associated Renal Cell Carcinoma
Abstract
We report a case of an isolated para-aortic retroperitoneal renal cell carcinoma (RCC) in the absence of a primary cancer in the kidney. Single case reports in the literature have described extra-renal RCC in different locations with no evidence of primary renal tumor. We present the initial presentation, diagnostic imaging, surgical treatment, and pathologic evaluation. Immunohistochemistry demonstrated positivity for TFE3 and TFEB, both of which are Microphthalmia associated transcription factors (MiT) associated with translocation RCCs. We hypothesize these few cases of extra-renal RCC represent rare forms of translocation RCC.
Clinical Trials Corner: A New Look at Cytoreductive Nephrectomy
Abstract
A Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial).
Status: Recruiting
Clinicaltrials.gov identifier: NCT04510597
Sponsor: Southwest Oncology Group
Enrollment: 364
Rationale: The benefit of cytoreductive nephrectomy (CN) had previously been established among fit patients with metastatic renal cell carcinoma. Subsequently, however, systemic therapy for mRCC evolved significantly. During the era of anti-angiogenesis therapy as first-line treatment, the CARMENA study supported the deferral of CN in patients receiving sunitinib who had intermediate or poor risk disease. However, subsequently, treatment of mRCC has further evolved, and with the new paradigm of immunotherapy-based combination treatment in the first-line setting, the role of cytoreductive nephrectomy remains in question.
Study Design: This Phase III randomized trial enrolls patients with histologically proven clear cell or non-clear cell RCC. Patients may be treatment naïve or have initiated systemic therapy in the locally advanced or metastatic setting up to 12 weeks prior to registration as long as scans documented metastatic disease prior. Patients with symptomatic brain metastases, solitary kidney, or kidney transplantation are excluded. Patients without progression on combination immunotherapy-based systemic therapy at 12 weeks will be randomized to continue on systemic immunotherapy or to undergo cytoreductive nephrectomy while continuing on systemic immunotherapy.
Endpoints: The primary endpoint of this trial is comparison of overall survival between patients receiving immune checkpoint inhibitor-based combination therapy alone versus those who receive immune checkpoint inhibitor-based combination therapy and cytoreductive nephrectomy. The secondary outcomes include assessing complications of nephrectomy and post-randomization drug toxicities, objective response rate in metastatic sites between arms, and assessing change in diameter of primary tumor at week 12 disease assessment.
