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ASCO GU 2021

ASCO GU 2021: Illustration of Temporal Evolution in Patients with mRCC Using Both ctDNA and Tissue-Based Genomic Data

(UroToday.com) Temporal and spatial heterogeneity have been consistently identified as contributing to perceived discordance between circulating tumor DNA and tissue-based assays. At the 2020 European Society of Medical Oncology Annual Congress, Zengin et al. previously demonstrated the feasibility of circulating tumor DNA assessment in metastatic renal cell carcinoma (mRCC) and preliminarily showed agreement between circulating tumor DNA and tissue-based genomic findings. This data suggested that the degree of agreement is dependent upon the temporal separation of blood and tissue samples. At the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, Dr. Zeynep Zengin and colleagues presented results of their study further exploring this temporal impact in a separate validation cohort.

ASCO GU 2021: Efficacy of Cabozantinib in Advanced MiT Family Translocation Renal Cell Carcinomas

(UroToday.com) MiT family translocation renal cell carcinomas represent a rare (1-5%) and aggressive subgroup of renal cell carcinoma (RCC) harboring high expression of c-MET. Additionally, these tumors are characterized by chromosomal translocations involving TFE3 and TFEB transcription factor genes. Currently, there are no standard treatments for these patients according to the National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines. For advanced disease, median progression-free survival with VEGF-targeted therapy in first-line varies between 3-8.4 months. While response rates of VEGF receptor tyrosine kinase inhibitor and immune checkpoint inhibitors are limited, the efficacy of cabozantinib (a tyrosine kinase inhibitor [TKI] that inhibits VEGFR, MET, and AXL) in this subgroup is unclear. At the the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, Dr. Jonathan Thouvenin and colleagues presented results of their study evaluating the efficacy of cabozantinib in advanced MiT family translocation renal cell carcinoma.

ASCO GU 2021: Sunitinib Versus Cabozantinib, Crizotinib or Savolitinib in Metastatic Papillary Renal Cell Carcinoma (pRCC): Results from the Randomized Phase II SWOG 1500 Study

(UroToday.com) While there has been a rapid proliferation of treatment options for patients with advanced renal cell carcinoma, these studies have focused on patients with clear cell histology. In contrast, there is a relative dearth of data for the treatment of advanced non-clear cell RCC. Therefore, patients with these tumors may receive agents on the basis of their activity in ccRCC. However, VEGF-receptor inhibitors have been shown to have relatively low activity in patients with papillary RCC (pRCC). However, MET signaling is a key molecular driver in pRCC. Given that there is no optimal therapy for metastatic pRCC, in a plenary abstract presentation in the Oral Abstract Session: Renal Cell Cancer session at the 2021 ASCO GU Cancers Symposium, Dr. Sumanta Pal and colleagues provide results of the SWOG 1500 study examining an existing standard (sunitinib) to putative MET kinase inhibitors in patients with pRCC. Notably, this study was concurrently published in The Lancet.1

ASCO GU 2021: Outcomes For Patients In the Pembrolizumab+Axitinib Arm With Advanced Renal Cell Carcinoma Who Completed Two Years Of Treatment In The Phase III KEYNOTE-426 Study

(UroToday.com) 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, the 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. The subsequent publication of the JAVELIN Renal 101, KEYNOTE-426, and CheckMate-9ER studies demonstrated the superiority of avelumab and axitinib, pembrolizumab and axitinib, and nivolumab and cabozantinib compared to sunitinib in this disease space. In a plenary abstract presentation in the Poster Highlights Session: Renal Cell Cancer - Clinical Trial Updates session at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU),  Dr. Plimack and colleagues provide an update on the KEYNOTE-426 study examining outcomes for patients who received pembrolizumab and axitinib and have completed two years of follow-up.

ASCO GU 2021: Patient-Reported Outcomes Of Patients With Advanced Renal Cell Carcinoma Treated With First-Line Nivolumab Plus Cabozantinib Versus Sunitinib: The Checkmate 9ER Trial

(UroToday.com) 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. Subsequent publication of the JAVELIN Renal 101 and KEYNOTE-426 studies in 2019 demonstrated superiority of avelumab and axitinib and pembrolizumab and axitinib, compared to sunitinib in this disease space. These two trials were the first to demonstrate that the combination of immunotherapy with checkpoint inhibition and targeted therapy improved overall survival compared to sunitinib, the previous standard of care. Network meta-analysis following publication of these data demonstrated the apparent superiority of this combined approach. At ESMO 2020, Dr. Choueiri presented first results from the CheckMate-9ER of the combination of nivolumab and cabozantinib, as compared to sunitinib, in the first-line treatment of patients with advanced or metastatic renal cell carcinoma. This first report, which is still unpublished, demonstrated the superiority of nivolumab plus cabozantinib to sunitinib in the first line treatment of patients with advanced renal cell carcinoma with respect to both progression-free survival and overall survival and led to its approval. In a plenary abstract presentation in the Poster Highlights Session: Renal Cell Cancer - Clinical Trial Updates session at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Cella presented patient-reported outcomes from this trial.

ASCO GU 2021: Nivolumab + Cabozantinib Versus Sunitinib for Advanced Renal Cell Carcinoma (aRCC): Outcomes by Sarcomatoid Histology and Updated Trial Results with Extended Follow-up of CheckMate 9ER

(UroToday.com) 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. The subsequent publication of the JAVELIN Renal 101 and KEYNOTE-426 studies in 2019 demonstrated the superiority of avelumab and axitinib and pembrolizumab and axitinib, compared to sunitinib in this disease space. These two trials were the first to demonstrate that the combination of immunotherapy with checkpoint inhibition and targeted therapy improved overall survival compared to sunitinib, the previous standard of care. Network meta-analysis following the publication of these data demonstrated the apparent superiority of this combined approach.

ASCO GU 2021: Efficacy and Safety of Avelumab plus Axitinib (A + Ax) Versus Sunitinib (S) in Elderly Patients with Advanced Renal Cell Carcinoma (aRCC): Extended Follow-up Results from JAVELIN Renal 101

(UroToday.com) 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. The subsequent publication of the JAVELIN Renal 101, KEYNOTE-426, and CheckMate-9ER studies demonstrated the superiority of avelumab and axitinib, pembrolizumab, and axitinib, and nivolumab and cabozantinib compared to sunitinib in this disease space. However, the role of immune checkpoint + VEGFR inhibition in elderly patients remains unclear. In a plenary abstract presentation in the Poster Highlights Session: Renal Cell Cancer - Clinical Trial Updates session at the 2021 ASCO GU Cancers Symposium, Dr. Yoshihiko Tomita and colleagues provide an update of the JAVELIN Renal 101 trial with a focus on efficacy and safety outcomes stratified by age.

ASCO GU 2021: Phase 2 Study of the Oral Hypoxia-Inducible Factor 2α (HIF-2α) Inhibitor MK-6482 in Combination with Cabozantinib in Patients with Advanced Clear Cell Renal Cell Carcinoma

(UroToday.com) As a part of the kindey cancer oral abstract session, Dr. Toni Choueiri presented preliminary results from a phase 2 study of belzutifan (MK-6482) in combination with United States Federal Drug Administration (FDA)-approved multiple TKI, cabozantinib.  As covered in other presentations throughout this year’s American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), greater than 90% of people with clear cell renal cell carcinoma (ccRCC) harbor sporadic genomic alterations resulting in defective VHL protein and a pseudohypoxic state.  This latter point is the basis of the rationale for targeting HIF2alpha with belzutifan.

ASCO GU 2021: Bench to Bedside: Critical Pathways in Renal Cell Carcinoma – Pathways to Detection

(UroToday.com) In this presentation, Dr. W. Kimryn Rathmell first discussed various genetic pathways that have been identified in renal cell carcinoma (RCC) and related these pathways to ongoing work trying to utilize imaging technologies and other noninvasive strategies for improved RCC classification and detection. 

ASCO GU 2021: Bench to Bedside: Critical Pathways in Renal Cell Carcinoma – Pathways to RCC Inception

(UroToday.com) Renal cell carcinoma (RCC) is a diverse group of diseases, as work from multiple recent studies at the genomic and transcriptomic level has highlighted. In this talk, Dr. Hakimi discussed what is known about the heterogeneity in pathways to RCC inception, focusing on clear cell RCC. 
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