Advanced Kidney Cancer COE Articles

Articles

  • A Multicentered, Propensity Matched Analysis Comparing Laparoscopic and Open Surgery for pT3a Renal Cell Carcinoma: Expert Commentary

    Laparoscopic renal surgery (LRS) has long been recognized for its improvements over open renal surgery for patient quality of life. However, LRS efficiency in terms of oncology and recurrences has yet to be compared. This team attempted to do just that by contrasting ORS and LRS on patients with Pathologic T3a (pT3a).
    Published September 15, 2017
  • ASCO 2021: A Quantum Leap in Cancer Adjuvant Immunotherapy - KEYNOTE 564 Phase 3 Trial - Discussion

    (UroToday.com) The much anticipated 2021 American Society of Clinical Oncology 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”.
    Published June 8, 2021
  • ASCO 2021: Pembrolizumab Versus Placebo As Post-Nephrectomy Adjuvant Therapy for Patients With Renal Cell Carcinoma: Randomized, Double-Blind, Phase III Keynote-564 Study

    (UroToday.com) Locally advanced renal cell carcinoma (RCC) can be surgically resected, but nearly half of patients eventually experience disease recurrence. Risk factors associated with relapse include larger tumors, higher tumor stage, nodal involvement, higher nuclear grade, and initial M1 presentation managed with complete surgical resection.
    Published June 10, 2021
  • ASCO 2022: LITESPARK-004 (MK-6482-004) Phase 2 Study of Belzutifan, an Oral HIF-2α Inhibitor, for Von Hippel-Lindau Disease: Update With More Than Two Years of Follow-Up Data

    (UroToday.com) 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. VHL disease is associated with malignant or benign tumors, including renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNETs), and hemangioblastomas. Alterations in the VHL gene cause aberrant stabilization and accumulation of HIF-2α, leading to the activation of genes associated with tumor growth. Antitumor activity observed in the ongoing open-label phase 2 study, LITESPARK-004 (NCT03401788), led to the approval of belzutifan for the treatment of patients with VHL disease who require therapy for associated RCC, CNS hemangioblastomas, or pNETs not requiring immediate surgery.1 At ASCO 2022, Dr. Jonasch presented updated results of this trial after > 2 years of follow-up.

    Published June 4, 2022
  • ASCO 2022: Pembrolizumab + Axitinib Versus Sunitinib As First-Line Therapy for Advanced Clear Cell RCC: Analysis of Progression After First Subsequent Therapy in KEYNOTE-426

    (UroToday.com) 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. The randomized, open-label, phase 3 KEYNOTE-426 study (NCT02853331)1 met its primary and key secondary end points of improved OS, PFS, and ORR with pembrolizumab + axitinib versus sunitinib as first-line treatment for patients with advanced clear cell RCC. Extended follow-up (42.8-month median follow-up) continued to show the superior efficacy of pembrolizumab + axitinib versus sunitinib in this patient population.2 This exploratory analysis compared the benefit of pembrolizumab + axitinib versus sunitinib beyond initial progression by evaluating PFS2 for all randomly assigned patients and across IMDC risk categories.

    Published June 5, 2022
  • ASCO GU 2021: Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab For Metastatic Genitourinary Tumors

    (UroToday.com) 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. In a plenary abstract presentation in the Rapid Abstract Session: Urothelial Carcinoma and Rare Tumors session at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Apolo presented results from a pooled analysis of the phase I dose-finding and 7 subsequent expansion cohorts among patients with metastatic genitourinary (mGU) tumors.
    Published February 13, 2021
  • 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.
    Published February 13, 2021
  • ASCO GU 2021: The CLEAR Study of Lenvatinib Plus Pembrolizumab or Everolimus vs Sunitinib and the SWOG 1500 Trial of Sunitinib, Cabozantinib, Crizotinib, and Savolitinib in Advanced Kidney Cancer: Discussion

    (UroToday.com) 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, Dr. Stephanie Berg provided a discussion of these data in the Oral Abstract Session: Renal Cell Cancer session at the 2021 ASCO GU Cancers Symposium.

    Published February 19, 2021
  • ASCO GU 2021: TIVO-3: Tivozanib in Patients with Advanced Renal Cell Carcinoma Who Have Progressed After Treatment with Axitinib

    (UroToday.com) Tivozanib is a potent and highly selective VEGF receptor tyrosine kinase inhibitor in clinical development for renal cell carcinoma (RCC). Axitinib is also a potent and selective VEGF-receptor inhibitor now commonly part of front-line advanced RCC treatment. In the TIVO-3 trial, tivozanib demonstrated significantly greater progression-free survival (PFS) (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56-0.94) and objective response rate (ORR) (15.2% versus 7.5%, p=0.003) versus sorafenib in the intention to treat population, in the subset of patients treated with two prior VEGFR-tyrosine kinase inhibitors (TKI), and in patients treated with a prior VEGFR-TKI and an anti-PD-1 antibody.1 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 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, 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.
    Published February 14, 2021
  • ASCO GU 2022: Efficacy and Safety of Lenvatinib Plus Pembrolizumab Versus Sunitinibin the East Asian Subset of Patients With Advanced Renal Cell Carcinoma From the Phase 3 CLEAR Trial

    (UroToday.com) In the 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).

    Published February 20, 2022
  • ASCO GU 2022: Efficacy, Safety, and Biomarker Analysis of Neoadjuvant Avelumab/Axitinib in Patients With Localized Renal Cell Carcinoma Who Are at High Risk of Relapse After Nephrectomy (NeoAvAx)

    (UroToday.com) In an oral abstract on the third day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 focused on renal cell cancer, Dr. Bex presented results of the NeoAvAx study examining neoadjuvant avelumab and axitinib following nephrectomy for patients who are at high risk for recurrence.

    Published February 20, 2022
  • ASCO GU 2022: HRQoL in Previously Untreated Patients With Advanced Renal Cell Carcinoma: CheckMate 9ER Updated Results

    (UroToday.com) 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. In CheckMate 9ER,1 patients with advanced RCC were randomized 1:1 to nivolumab 240 mg IV Q2W + cabozantinib 40 mg PO QD n = 323) or sunitinib 50 mg PO (4 weeks of 6-week cycles; n = 328). As reported previously, at a median follow-up of 18.1 months, nivolumab + cabozantinib led to superior progression-free and overall survival and more favorable HRQoL than sunitinib. At the 2022 GU ASCO meeting, Dr. Cella reported results of HRQoL analyses for 32.9-months follow-up.

    Published February 20, 2022
  • ASCO GU 2022: Pembrolizumab As Post Nephrectomy Adjuvant Therapy for Patients With Renal Cell Carcinoma: Results From 30-Month Follow-Up of KEYNOTE-564

    (UroToday.com) In an oral abstract on the third day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 focused on renal cell cancer, Dr. Choueiri presented 30-month follow-up from the KEYNOTE-564 trial of post-nephrectomy adjuvant pembrolizumab in patients with renal cell carcinoma (RCC).

    Published February 20, 2022
  • ASCO GU 2022: PIVOT IO 011: A Phase 1/2 Study of Bempegaldesleukin Plus Nivolumab and TKI Versus Nivolumab and TKI Alone in Patients With Previously Untreated Advanced or mRCC

    (UroToday.com) The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) trials in progress session featuring PIVOT IO 011, presented by Dr. Martin Voss, 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.

    Published February 20, 2022
  • ASCO GU 2022: Real-World Assessment of Changing Treatment Patterns and Sequence for Patients With Metastatic RCC in the First-Line Setting

    (UroToday.com) The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session highlighting work from Dr. Neil Shah and colleagues presenting results of a real-world assessment of changing treatment patterns and sequence for patients with metastatic RCC in the first-line setting. Several immune-oncology (IO) agents and/or tyrosine kinase inhibitors (TKIs) have received approval for treatment of metastatic RCC in the first-line setting by Food and Drug Administration (FDA) over last few years. Limited data exists on evolving real-world treatment patterns and sequences in metastatic RCC patients receiving these agents, especially in the community oncology setting.

    Published February 19, 2022
  • ASCO GU: TiNivo-2: Comparing Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Who Have Progressed Following One or Two Lines of Therapy Where One Line Has an Immune Checkpoint Inhibitor

    (UroToday.com) In a poster presentation on the third day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 on Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers, Dr. 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.

    Published February 19, 2022
  • Association of Baseline Neutrophil-to-Eosinophil Ratio with Response to Nivolumab plus Ipilimumab in Patients with Metastatic Renal Cell Carcinoma - Beyond the Abstract

    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 likely to respond to immunotherapy may help limit the number of patients who require upfront and long-term exposure to VEGF-TKIs. Additionally, the identification of biomarkers may help further our understanding of the tumor microenvironment (TME), enabling new mechanisms and combinations to improve outcomes for patients.

    Published November 22, 2021
  • AUA 2022: Is Cytoreductive Nephrectomy Dead or Alive in 2022?

    (UroToday.com) 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. From a historical perspective, Dr. Shapiro notes that in a combined analysis of SWOG 8949 and EORTC 30947, the median overall survival for cytoreductive nephrectomy + IFN-alpha was 13 months and for IFN-alpha alone was 7.8 months (p = 0.001). Benefits of cytoreductive nephrectomy include improved survival, and can also be important for symptomatic/palliative reasons. Of note, among all of the systemic therapy trials for metastatic RCC, the majority of patients had a prior nephrectomy:

    Published May 15, 2022
  • Avelumab Plus Axitinib Significantly Improved Progression-Free Survival In Previously Untreated Patients with Advanced Renal Cell Carcinoma in Phase III Study

    San Francisco, CA (UroToday.com) -- Merck KGaA, Darmstadt, Germany, and Pfizer Inc. announced positive top-line results from the pivotal Phase III JAVELIN Renal 101 study evaluating BAVENCIO® (avelumab) in combination with INLYTA® (axitinib), compared with SUTENT® (sunitinib) as initial therapy for patients with advanced renal cell carcinoma (RCC). As part of a planned interim analysis, an independent Data Monitoring Committee confirmed that the trial showed a statistically significant improvement in progression-free survival (PFS) by central review for patients treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).
    Published September 12, 2018
  • Axitinib Versus Placebo as an Adjuvant Treatment for Renal Cell Carcinoma: Results From the ATLAS Trial

    The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. 

    Patients and Methods

    In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease (independent review committee [IRC] confirmed). The intent-to-treat population included all randomized patients (≥pT2 and/or N+, any Fuhrman grade [FG], Eastern Cooperative Oncology Group status 0/1). Patients (stratified by risk group/country) received (1:1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted.

    Published October 20, 2018
  • Biomarker-Based Phase II Trial of Savolitinib in Patients with Advanced Papillary Renal Cell Cancer

    PURPOSE: Patients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status.
    Published December 9, 2018
  • Cabozantinib versus Everolimus in Advanced Renal Cell Carcinoma (METEOR): Final Results from a Randomised, Open-label, Phase 3 Trial

    BACKGROUND: Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment. Here, we report the final overall survival results from this study based on an unplanned second interim analysis. 
    Published December 3, 2018
  • Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

    BACKGROUND: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. 
    Published December 3, 2018
  • Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial

    Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC.
    Published September 11, 2017
  • Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial.

    Purpose Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC.

    Published March 19, 2018
  • EAU 2019: Post-Nephrectomy Adjuvant Therapy for Localized Renal Cell Carcinoma: CheckMate 914 Study of Nivolumab + Ipilimumab in Patients at High Risk of Relapse

    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 trials in patients with advanced localized RCC with targeted therapies (sutent, sorafenib, axitinib, pazopanib) have been either negative – or slightly positive and associated with significant adverse events.
    Published March 19, 2019
  • EAU 2019: The Challenging Landscape in Advanced Renal Cell Cancer Management

    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 and provided the following two figures based on the: 
    Published March 18, 2019
  • EIKCS 2021: Designing Biomarker-Driven Trials: Opportunities and Challenges

    (UroToday.com) The treatment landscape in the first-line therapy of metastatic renal cell carcinoma (mRCC) has rapidly evolved over the past 3 years. In spite of all these changes, more changes are coming. In a presentation at the European International Kidney Cancer 2021 Virtual Annual Meeting, Dr. Vano discussed biomarker-driven trials.
    Published April 24, 2021
  • EIKCS 2021: Kidney Cancer as a Model for a Curable Neoplasm

    (UroToday.com) 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. 

    Published April 24, 2021
  • EIKCS 2021: Modern Therapeutic Approaches in Second-Line and Later Therapies

    (UroToday.com) The treatment landscape in the first-line therapy of metastatic renal cell carcinoma (mRCC) has rapidly evolved over the past 3 years. This proliferation of first-line treatment choices has had meaningful effects on second-line treatment selection.
    Published April 23, 2021
  • EIKCS 2021: Tissue-Based Biomarkers for Potential Clinical Adoption in Renal Cancer

    (UroToday.com) 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.
    Published April 24, 2021
  • EIKCS 2022: ‘Real World’ Impact of Immune Checkpoint Inhibitors on Survival in Metastatic Renal Cell Carcinoma

    (UroToday.com) 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. Real world evidence is important given that few patients are able to enroll in clinical trials, thus assessing these outcomes provides a pragmatic evaluation of utilization across the community. For this study, Dr. Ince and colleagues queried an electronic health record metastatic RCC database at their institution from January 2012 through July 2020, comparing survival among patients that received immune checkpoint inhibitors vs those patients that did not receive immune checkpoint inhibitors. Key data collected included lines of treatment, survival, age, ECOG status, and IMDC criteria.

    Published April 22, 2022
  • EIKCS 2022: Debate: In Favor of Clinical Considerations and Challenges in Selecting Later-line Therapies

    (UroToday.com) 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. Albiges presented second, emphasizing clinical considerations to guide second line treatment approaches. She suggested that there are at least four main considerations:
    Published April 22, 2022
  • EIKCS 2022: Debate: In Favor of Evidence-based Treatment in the 2nd and 3rd Line

    (UroToday.com) 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.

    Published April 22, 2022
  • EIKCS 2022: Debate: In Favor of IO/IO

    (UroToday.com) 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.

    Published April 22, 2022
  • EIKCS 2022: Debate: In Favor of IO/TKI

    (UroToday.com) 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). In contextualizing this debate, she asked “what we want to achieve in first-line treatment of mRCC?”. She emphasized that we should be seeking to obtain the best outcomes for most patients. To this end, she highlighted “conventional endpoints” including control or shrinkage of cancer, the disappearance of cancer or cure, minimizing symptoms from cancer, minimizing side effects from treatment, and maximizing quality of life. These considerations must be premised on the basis of the fact that we do not have reliable predictive markers to select therapy at an individual level.

    Published April 22, 2022
  • EIKCS 2022: Nivolumab + Ipilimumab + Cabozantinib for Previously Untreated Advanced RCC: Results from a Discontinued Study Arm of CheckMate 9ER

    (UroToday.com) 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. Dr. Escudier notes that the CheckMate 9ER trial1 originally included three treatment arms to compare outcomes for nivolumab + cabozantinib versus sunitinib and nivolumab + ipilimumab + cabozantinib versus sunitinib. Shortly after CheckMate 9ER began, data from CheckMate 2142 demonstrated the OS superiority of nivolumab + ipilimumab versus sunitinib for patients with IMDC intermediate- or poor-risk untreated advanced RCC, suggesting a likely future role for nivolumab + ipilimumab as standard of care for this population. Based on this evolving advanced RCC treatment landscape, evaluation of nivolumab + ipilimumab + cabozantinib versus sunitinib was no longer considered appropriate, and the CheckMate 9ER triplet arm was discontinued early via a protocol amendment.

    Published April 22, 2022
  • ESMO 2018: Safety and Tolerability of Atezolizumab plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma: IMmotion 150 and IMmotion 151

    Munich, Germany (UroToday.com) IMmotion 150 (Phase II) compared the efficacy of atezolizumab (atezo) plus bevacizumab (bev) with atezolizumab alone and sunitinib alone and then allowed for crossover in the latter 2 arms to atezolizumab plus bevacizumab.1 IMmotion 151  (Phase III) compared the efficacy of atezolizumab plus bevacizumab vs sunitinib for first-line therapy of metastatic renal cell carcinoma2.
    Published October 22, 2018
  • ESMO 2019: Adjuvant Sorafenib for Renal Cell Carcinoma at Intermediate or High Risk of Relapse, Results from the SORCE Trial

    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). Only S-TRAC met the primary endpoint of improvement in disease-free survival (DFS). None of these studies demonstrated improvement in overall survival (OS). Dr. Tim Eisen presents the primary efficacy results from the SORCE trial, an international, randomized, double-blind Phase 3 trial that evaluated adjuvant sorafenib for RCC at intermediate or high risk of relapse.

    Published September 28, 2019
  • ESMO 2021: Cabozantinib-Nivolumab Versus Nivolumab-Cabozantinib in Patients With Metastatic Clear Cell RCC Following One Prior VEGFR TKI: The CABIR Multicenter Matching-Adjusted Study

    (UroToday.com) The European Society of Medical Oncology (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. However, the optimal sequence, cabozantinib-nivolumab or nivolumab-cabozantinib, is still unknown. The superiority of cabozantinib over everolimus in patients with prior anti-PD-1 (HR 0.22, 95% CI 0.07-0.65) in the METEOR trial suggests a sensitizing role of nivolumab.1 At the 2021 ESMO congress, Dr. Vano and colleagues presented results of the CABIR study to identify the optimal sequence between cabozantinib-nivolumab and nivolumab-cabozantinib after one prior TKI.

    Published September 18, 2021
  • ESMO 2021: Conditional Survival and 5-Year Follow-Up in CheckMate 214: First-Line Nivolumab + Ipilimumab Versus Sunitinib in Advanced RCC

    (UroToday.com) The European Society of Medical Oncology (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. The combination of nivolumab + ipilimumab is approved by the European Commission and the US FDA for first-line treatment of patients with advanced RCC with IMDC intermediate/poor risk disease, based on superior overall survival (OS) and objective response rate (ORR) over sunitinib in the randomized, phase 3 CheckMate 214 trial.1 Conditional survival, used to predict sustained treatment benefit, accounts for time since treatment initiation and provides improved prognostic information at landmark time points. Conditional survival in advanced RCC patients was estimated in CheckMate 214 with a minimum 5-years of follow-up (median follow-up, 67.7 months).

    Published September 18, 2021
  • ESMO 2021: Nivolumab in Combination With Alternatively Scheduled Ipilimumab in First-Line Treatment of Patients With Advanced RCC: A Randomized Phase II Trial (PRISM)

    (UroToday.com) The European Society of Medical Oncology (ESMO) 2021 virtual 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). Ipilimumab plus nivolumab is a standard first-line treatment for patients with intermediate and poor-risk advanced RCC based on data from the CheckMate 214 trial.1 Grade 3/4 treatment-related adverse events are relatively common during the initial combination period, including 47% of patients experiencing a grade 3/4 treatment-related adverse event and 22% of patients discontinuing treatment due to treatment-related adverse events in the CheckMate 214 trial. The aim of this randomized phase II trial was to determine whether modified scheduling of ipilimumab, in combination with nivolumab, is associated with improved tolerability, while maintaining treatment efficacy in line with previous comparative studies with sunitinib.

    Patients with untreated clear cell advanced RCC were randomized 1:2 to receive 4 doses of ipilimumab 1mg/kg Q3W (conventional ipilimumab) or Q12W (modified ipilimumab), in combination with nivolumab (3mg/kg), until disease progression or unacceptable toxicity. The study design for PRISM is as follows:

     

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    As follows is a summary of the treatment schedule in PRISM:

     

    image-1.jpg 

     

    The primary endpoint was the proportion of patients with a grade 3/4 treatment-related adverse events within 12 months of initiating treatment (from those who received at least one dose of therapy (modified intention-to-treat)). Secondary endpoints included progression-free survival (PFS) at 12 months tested against the historical PFS associated with sunitinib and objective response rate (ORR).

     There were 192 patients (69.8% intermediate/poor-risk), including 128 patients in the modified ipilimumab arm and 64 patients in the standard ipilimumab arm, that received at least one dose of study drug. The median follow-up for the cohort was 19.7 months IQR: 15.9-23.6 months). Grade 3/4 treatment-related adverse events were significantly lower amongst patients receiving modified ipilimumab compared to conventional ipilimumab (32.8% versus 53.1%; OR 0.43, 90% CI 0.25, 0.72):

     

    image-2.jpg 

     

    The most common grade 3/4 adverse events in the modified ipilimumab group was diarrhea (5.5%) and ALT increase (4.7%), whereas the most common grade 3/4 adverse events in the standard ipilimumab arm was arthralgia (7.8%), and diarrhea (4.7%). 12-month PFS rate was 46.1% (90% CI 38.6-53.2%) in the modified ipilimumab compared to the sunitinib historical rate of 39.7%; median PFS in the modified ipilimumab arm was 10.8 months (95% CI 8.2-14.2) compared to 9.8 months (95% CI 9.8-13.3) in the standard ipilimumab arm. Median PFS in the IMDC intermediate/poor risk group was 10.5 months for the modified ipilimumab arm (90% 7.0-14.2) compared to 8.6 months (90% 6.0-16.3) in the standard ipilimumab arm. In the intention-to-treat analysis, the ORR in for the modified ipilimumab arm was 45.3% (95% CI 36.7-53.9) compared to 35.9% (95% CI 24.2-47.7) in the standard ipilimumab. As follows is the summary of the treatment responses:

     

    image-3.jpg 

     

    Although with limited follow-up, the median OS in either arm was not reached, however the 12-month landmark OS rate was 88.3% for the modified ipilimumab arm compared to 83.7% in the standard ipilimumab arm.

     

    Dr. Vasudev concluded his presentation of the PRISM trial with the following take-home messages:

    • Giving ipilimumab 12-weekly, instead of 3-weekly, in combination with nivolumab, was associated with a clinically significant reduction in rates of grade 3/4 treatment-related adverse events (33% versus 53%)
    • The lower limit of the confidence interval for 12 month PFS observed with modified ipilimumab failed to exclude the rate associated with historical control data (sunitinib)
    • However, median PFS, ORR, duration of response and 12-month landmark OS results were comparable between treatment arms
    • This positive phase 2 trial supports further exploration of different nivolumab/ipilimumab regimes

     

    Presented by: Naveen S. Vasudev, PhD, MRCP, MBChB, BMSc (Hons), Medical Oncology Department, St. James's University Hospital Leeds, Leeds, UK

    Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter  during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.

    References:

    1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 2018;378(14):1277-1290.

     

    Published September 19, 2021
  • ESMO 2021: Pembrolizumab vs Placebo As Adjuvant Therapy for Patients With Renal Cell Carcinoma: Patient-Reported Outcomes in KEYNOTE-564

    (UroToday.com) 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). Results of the KEYNOTE-564 trial, initially presented at the ASCO 2021 Annual Meeting and recently published in the New England Journal of Medicine, demonstrated an improvement in disease-free survival at 24 months for patients randomized to receive adjuvant Pembrolizumab (77.3%) versus placebo (68.1%) (HR 0.68, 95% CI 0.53-0.87; P = 0.002).1 Overall survival data was immature and did not cross the pre-specified statistical threshold for this preliminary analysis, but at 24 month trended towards improvement for patients on the Pembrolizumab (96.6%) compared to the placebo (93.5%) arm (HR 0.54, 95% CI 0.30-0.96; P = 0.0164).

    Published September 19, 2021
  • ESMO 2021: Phase 3 CLEAR Trial in Advanced Renal Cell Carcinoma: Outcomes in Subgroups and Toxicity Update

    (UroToday.com) The European Society of Medical Oncology (ESMO) 2021 virtual 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). In the CLEAR trial, lenvatinib + pembrolizumab demonstrated significant improvement in PFS (24 months versus 9 months; HR 0.39, 95% CI 0.32-0.49), OS (not reached in either arm; HR 0.66, 95% CI 0.49-0.88), and ORR (71% versus 36%; OR 4.35, 95% CI 3.16-5.97) versus sunitinib for patients with advanced RCC. The analysis reported at the 2021 ESMO virtual congress explored efficacy outcomes in patients with or without adverse pathologic features (ie. sarcomatoid histology, bone metastases, liver metastases, and no prior nephrectomy) in the lenvatinib + pembrolizumab versus sunitinib arms. Additionally, the number of patients who received high-dose corticosteroids to manage immune-related adverse events is reported.

    Published September 18, 2021
  • ESMO 2021: Randomized, Open-Label, 3-Arm Phase 3 Study Comparing MK-1308A + Lenvatinib and Pembrolizumab + Belzutifan + Lenvatinib versus Pembrolizumab + Lenvatinib as First-line Treatment for Advanced Clear Cell RCC

    (UroToday.com) The European Society of Medical Oncology (ESMO) 2021 virtual 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. Despite advances in treatment, most patients with advanced clear cell RCC will eventually experience disease progression on treatment. Combination therapy with the PD-1 inhibitor pembrolizumab and the VEGF inhibitor lenvatinib showed activity in patients with advanced ccRCC in the phase III KEYNOTE-581/CLEAR trial.1 The HIF-2α inhibitor belzutifan (MK-6482) and MK-1308A, a coformulation of pembrolizumab and the CTLA-4 inhibitor quavonlimab, have each shown antitumor activity in phase I/II trials. HIF-2α or CTLA-4 inhibition with PD-1 and VEGF inhibition backbone combination may provide additional benefit as first-line treatment in clear cell RCC.

    Published September 18, 2021
  • ESMO 2022: Efficacy of a Tailored Approach With Nivolumab and Nivolumab/ipilimumab as Immunotherapeutic Boost in Metastatic Renal Cell Carcinoma – Final Results of TITAN-RCC

    (UroToday.com) On Sunday, September 11,2022, in the Mini Oral session of the European Society for Medical Oncology (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). A combination immune checkpoint inhibitor approach with nivolumab 3 mg/kg + ipilimumab 1 mg/kg (nivo+ipi) is an approved first-line treatment approach in mRCC and intermediate / poor risk disease. However, there is significant toxicity so a tailored approach has been assessed in a number of trials.

    TITAN-RCC included patients receiving both first-line treatment and second-line treatment following initial tyrosine kinase inhibitors. The study used a response-based approach with nivo induction and nivo+ipi boost in non-responders.

    ESMO 2022_Marc-Oliver Grimm_TITAN-RCC trial_0 

    Between October 2016 and December 2018, 207 patients with intermediate/poor risk mRCC started initial nivo induction (Q2W, 240 mg). Patients with early progressive disease (PD, week 8) or non-responders at week 16 (stable disease [SD]/PD) received 2 to 4 doses of nivo+ipi. In contrast, those who were initial responders to nivo induction (complete/partial response [CR/PR]) continued with nivo maintenance but could receive nivo+ipi for later progressive disease. The primary endpoint was confirmed objective response rate (ORR) per RECIST in both the first- and second-line setting. Secondary endpoints included efficacy of nivo induction, response to boost, progression free (PFS) and overall survival (OS), and safety.

    Among 207 enrolled patients, 109 were treated in the first-line setting and 98 were treated following initial TKI therapy. Among included patients, the median age was 65 years of age. Among the 207 patients, 71 % had intermediate and 25 % had poor risk disease.

    A confirmed response to nivo induction was seen in 28% of patients in the first-line and 18% in the second-line setting. After 33.6 months from last patient’s first treatment and at 15.9 months median follow-up, the objective response rate for nivo ± nivo+ipi was 36% in the first-line setting (significant >25 %, p<0.05) and 32% in the second-line setting.

    ESMO 2022_Marc-Oliver Grimm_TITAN-RCC trial_1 

    Whether due to initial early progressive disease or non-response or a delayed progressive disease, 44% of patients who started first-line therapy with nivo monotherapy and 53% of patients in the second-line setting received ipi boosts for PD improved in best response.

    ESMO 2022_Marc-Oliver Grimm_TITAN-RCC trial_2 

    Progression-free survival was 6.3 months (95 % CI 3.7-10.1) in first-line and 3.7 months (95 % CI 1.8-4.5) in second-line. Correspondingly, overall survival was 32.0 months (95 % CI 22.9-39.4) in first-line and 25.9 months (95 % CI 17.8-33.7) in second-line.

    ESMO 2022_Marc-Oliver Grimm_TITAN-RCC trial_3 

    With this final analysis, the authors identified no new safety signals.

    Dr. Grimm concluded the nivo+ipi boosts following initial nivo monotherapy improve outcomes. While there was demonstrated potential with ipilimumab as a rescue strategy, these outcomes are inferior to initial upfront combination therapy. Thus, this tailored approach is not recommended.


    Presented by: Marc-Oliver Grimm, MD, Professor and Chairman at Universitätsklinikum Jena, Jena, Germany


    Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.

     

     Related Content: 
    ESMO 2022: Updated Results From the CLEAR Trial and the Final Results of TITAN-RCC Discussion

    Published September 12, 2022
  • ESMO 2022: Phase 3 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Previously Untreated Advanced Renal Cell Carcinoma of IMDC Intermediate or Poor Risk (COSMIC-313)

    (UroToday.com) On Monday, September 12, 2022, in Presidential Symposium III at the European Society for Medical Oncology (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).

    Published September 12, 2022
  • ESMO 2022: Updated Efficacy of Lenvatinib + Pembrolizumab Vs Sunitinib in Patients With Advanced Renal Cell Carcinoma in the CLEAR Study

    (UroToday.com) On Sunday, September 11, 2022, in the Mini Oral session of the European Society for Medical Oncology (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). In the primary analysis, there was significantly improved progression-free survival and overall survival in patients treated with the combination approach.

    Published September 11, 2022
  • ESMO 2022: Updated Results From the CLEAR Trial and the Final Results of TITAN-RCC Discussion

    (UroToday.com) 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.

    Published September 12, 2022
  • ESMO Virtual Congress 2020: Results From the Phase 2 BIOmarker Driven Trial with Nivolumab and Ipilimumab or VEGFR TKI in Naïve Metastatic Kidney Cancer: the BIONIKK Trial

    (UroToday.com)  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. Combination nivolumab and ipilimumab resulted in a 42% objective response rate and median progression-free survival of 11.6 months. Single-agent nivolumab is associated with an objective response rate of 28.7% with a median progression-free survival of 5.54 months. A recent transcriptomic analysis of primary frozen ccRCC specimens revealed 4 molecular subgroups that could be summarized by a 35 gene signature (ccrcc1-ccrcc4). Ccrcc1 (immune-low) and ccrcc4 (immune-high) were associated with the poorest outcomes to sunitinib, whereas ccrcc2 (angio-high) and ccrcc3 (normal-like) had the best outcomes. The authors of this presentation hypothesized that these expression signatures could stratify patients most likely to respond to sunitinib (ccrcc2, angio-high, and ccrcc3), nivolumab (ccrcc4,immune-high), and nivolumab and ipilimumab (ccrcc1, immune-low).

    Published September 22, 2020

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