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Advanced Kidney Cancer COE

  • ESMO 2017: CheckMate 214: Efficacy and safety of Nivolumab + Ipilimumab vs Sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups

    Madrid, Spain (UroToday.com) Professor Escudier and colleagues presented results of their phase III CheckMate 214 trial assessing nivolumab + ipilimumab vs sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC). Nivolumab plus the CTLA-4 inhibitor ipilimumab combination previously demonstrated safety and high antitumor activity in previously treated and treatment-naïve patients with mRCC in the phase Ib CheckMate 016 study [1].
    Published September 11, 2017
  • A Phase l/ll Open-Label, Dose Escalation, Safety and Activity Study of the Antibody-Drug Conjugate CDX-014 in Advanced or Metastatic Renal Cell Carcinoma (RCC)

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    A Phase l Open-Label, Dose Escalation and Cohort Expansion Study, to Assess the Safety and Activity of the Antibody-Drug Conjugate CDX-014 in Advanced or Metastatic Renal Cell Carcinoma (RCC) and Advanced or Metastatic Ovarian Clear Cell Carcinoma (OCCC)


    Condition: Renal Cell Carcinoma (RCC), Clear-cell Renal Cell Carcinoma, Papillary Renal Cell Carcinoma, Kidney Neoplasms, Metastatic Renal Cell Carcinoma, Ovarian Clear Cell Carcinoma

    Intervention:

    • Drug: CDX-014

    Purpose: This is a study to determine the safety of CDX-014 and effectiveness (how well the drug works).

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02837991

    Sponsor: Celldex Therapeutics

    Primary Outcome Measures:

    • Measure: Dose Escalation - Determine Maximum Tolerated Dose (MTD)
    • Time Frame: Within 21 days after first dose.
    • Safety Issue:
    • Measure: Cohort Expansion - Assess Objective Response Rate (ORR)
    • Time Frame: Evaluated every 6-9 weeks following treatment initiation until treatment is discontinued or disease progression, up to 5 years.
    • Safety Issue:

    Estimated Enrollment: 125

    Study Start Date: June 2016

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Histologically confirmed diagnosis of advanced or metastatic clear cell or papillary renal cell carcinoma or histologically confirmed clear cell ovarian carcinoma.
    2. For RCC, at least two prior anticancer regimens (one must be a VEGF-targeted TKI), or are otherwise inappropriate candidates for all approved therapies. For OCCC, at least one line of prior therapy with a platinum and taxane regimen.
    3. Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
    4. Measureable (target) disease.
    5. Must have available tumor tissue for TIM-1 expression testing
    6. Life expectancy ≥ 3 months
    7. If of childbearing potential (male or female), agrees to use effective contraception during study treatment and for at least 6 months following last treatment dose.

    Exclusion Criteria:

    1. Prior therapy containing MMAE
    2. Any prior cytotoxic chemotherapy regimen, including antibody drug conjugates for RCC or cytotoxic chemotherapy within 3 weeks of study treatment for OCCC
    3. Tyrosine kinase inhibitor (TKI) therapy within 2 weeks or at least 5 half-lives (whichever is longer) prior to planned start of study treatment.
    4. Monoclonal antibody therapy within 4 weeks prior to the planned start of study treatment.
    5. Radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed up to 2 weeks prior to study treatment start).
    6. Major surgery or significant traumatic injury within 4 weeks prior to study entry.
    7. Use of other investigational drugs within 2 weeks or 5 half-lives (whichever is longer) prior to study treatment.
    8. Concurrent severe and/or uncontrolled medical conditions (uncontrolled diabetes or infection), known infection with HIV, Hepatitis B or Hepatitis C.
    9. Brain metastases, unless previously treated and asymptomatic and not progressive for 2 months.
    10. Significant cardiovascular disease (including congestive heart failure).
    11. Other malignancy except for treated and cured basal or squamous cell skin cancer, cured in situ cancers, or other cancer from which the patient has been disease-free for ≥ 3 years.
    12. Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary.
    13. Chronic use of systemic corticosteroid above an accepted physiologic dose (5mg per day of prednisone or equivalent) within 7 days of enrollment except when used as premedication

    Contact:

    • Celldex Therapeutics

    Locations:

    • HonorHealth Research Institute
    • Scottsdale Arizona 85258 United States
    • USC/Norris Comprehensive Cancer Center
    • Los Angeles California 90033 United States
    • Dana Farber Cancer Institute
    • Boston Massachusetts 02215 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14263 United States
    • Huntsman Cancer Institute
    • Salt Lake City Utah 84112 United States

    View trial on ClinicalTrials.gov


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    Published July 29, 2017
  • ASCO 2017: Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with locally advanced renal cell carcinoma (RCC) (PROTECT)

    Chicago, IL (UroToday.com) On the heels of two randomized controlled trials (RCTs) recently published assessing adjuvant TKIs in the setting of patients treated with radical nephrectomy for locally advanced renal cell carcinoma (RCC) [1,2], Dr. Motzer and colleagues presented their findings at the 2017 ASCO annual meeting of another phase III RCT assessing adjuvant pazopanib vs placebo in these high risk patients.
    Published June 5, 2017
  • ASCO 2018: A Phase 3, Randomized, Open-label Study of Nivolumab Combined with Cabozantinib vs Sunitinib in Patients with Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

    Chicago, IL (UroToday.com) Current standard of care for advanced or metastatic renal cell carcinoma (RCC) includes a collection of agents targeting the vascular endothelial growth factor (VEGF) pathway, anchored by the tyrosine kinase inhibitors sunitinib and sorafenib. Other agents affecting this pathway encompass the first, second and even third-line options. Unfortunately, these medications are not curative and are effectively not cytotoxic. Cytotoxic chemotherapy has proven ineffective in this disease space.
    Published June 3, 2018
  • ASCO 2018: CABOPRE: Phase II Study of Cabozantinib Prior to Cytoreductive Nephrectomy in Locally Advanced and/or Metastatic Renal Cell Carcinoma

    Chicago, IL (UroToday.com) The current standard of care for patients with metastatic RCC is cytoreductive nephrectomy, followed by vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy. With this type of therapy, patients need to recover from their surgery before starting TKI therapy. Up to 50% of patients do not receive TKI therapy in a timely manner.
    Published June 6, 2018
  • ASCO 2018: CARMENA: Cytoreductive Nephrectomy Followed by Sunitinib vs. Sunitinib Alone in Metastatic Renal Cell Carcinoma - Results of a Phase III Noninferiority Trial

    Chicago, IL (UroToday.com) Over the past 2 decades, cytoreductive nephrectomy (CN) has been a reasonable treatment option for carefully selected patients with metastatic renal cell carcinoma (mRCC). While there is no universal list of criteria, clinical trials have demonstrated that those patients with an estimated survival of less than 12 months or those with four or more IMDC criteria (Anemia, Thrombocytosis, Neutrophilia, Karnofsky Performance Status (KPS) <80 percent, <1 year from diagnosis to treatment) may not benefit from nephrectomy1.
    Published June 3, 2018
  • ASCO 2018: Optimizing Systemic Therapy in Advanced Renal Cell Carcinoma

    Chicago, IL (UroToday.com) Toni Choueiri, MD, provided a discussion following three Renal Cell Carcinoma (RCC) oral abstracts presented at the 2018 ASCO annual meeting. The first study was results of the KEYNOTE-427 studypresented by David F. McDermott, MD. This study evaluated monotherapy pembrolizumab as first-line therapy for patients with mRCC, noting promising antitumor activity for pembrolizumab treating clear cell RCC across IMDC risk groups with an ORR of 38%.
    Published June 4, 2018
  • ASCO 2018: Prospective, Multinational, Observational Study of Real-World Treatment Outcomes with Pazopanib in Patients with Advanced or Metastatic Renal Cell Carcinoma (Principal Study)

    Chicago, IL (UroToday.com) Pazopanib and Sunitinib are vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs), which are established as first-line treatment options for patients with advanced or metastatic renal cell carcinoma (RCC). Pazopanib has been approved for the treatment of patients with advanced RCC, after a publication of a randomized phase 3 trial [1], showing pazopanib having a clear benefit compared to placebo in progression free survival (PFS). Other trials, such as the COMPARZ [2] and PISCES [3] compared pazopanib to sunitinib, showing that pazopanib had non-inferior efficacy and improved quality of life. Furthermore, patients and physicians preferred pazopanib over sunitinib. [3]
    Published June 5, 2018
  • ASCO 2018: PROSPER: A Phase III Randomized Study Comparing Perioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy

    Chicago, IL (UroToday.com) Not to be confused with the recent PROSPER trial for prostate cancer, this trial continues the trend of expanding the indications for immune checkpoint inhibitors in various stages of different GU malignancies.
    Adjuvant therapy for high-risk localized renal cell carcinoma patients following radical neprectomy has been a controversial topic – conflicting results using tyrosine-kinase inhibitors (TKI’s) have resulted in uncertainty into their use. One study (S-TRAC) demonstrated DFS benefit, while three other studies (ASSURE, PROTECT and the soon to be reported ATLAS) demonstrated no benefit. So, while sunitinib is FDA-approved in this setting, utilization has been limited. In fact, guidelines primarily recommend clinical trial enrollment.
    Published June 3, 2018
  • ASCO 2018: Sunitinib Alone Shows Non-inferiority Versus Standard of Care in mRCC - The CARMENA Study

    Chicago, IL (UroToday.com) Cytoreductive nephrectomy, essentially debulking of the primary tumor in the setting of metastatic renal cell carcinoma (mRCC), has been a mainstay of therapy for decades. In the IL-2/immunomodulator era, Flanigan et al. (NEJM 2001, JUrol 2004) and Mickisch et al. (Lancet 2001) demonstrated that removal of the kidney was associated with improved overall survival (OS). As a result, it has become an established paradigm in the management of mRCC, and patients who are surgically fit, are often recommended for cytoreductive nephrectomy prior to systemic therapy.
    Published June 3, 2018
  • ASCO GU 2017: A phase II study of atezolizumab (atezo) with or without bevacizumab (bev) versus sunitinib (sun) in untreated metastatic renal cell carcinoma (mRCC) patients (pts). - Session Highlights

    Orlando, Florida USA (UroToday.com) Dr. Powles presented a multi-institutional randomized phase II study evaluating the efficacy of first line therapies in metastatic renal cell carcinoma (mRCC). It is the first study of its kind comparing immune checkpoint + targeted therapy with antiangiogenic monontherapy.
    Published February 18, 2017
  • ASCO GU 2017: Adjuvant Therapy of Renal Cell Carcinoma: Current Controversies - Session Highlights

    Orlando, Florida USA (UroToday.com) In this session, Dr. Karam reported the current controversies in adjuvant management of renal cell carcinoma (RCC). The ideal adjuvant setting is a patient at high risk for recurrence, a drug active on microscopic cancer, low drug toxicity, inexpensive cost, and derivation of a clinically meaningful outcome.
    Published February 18, 2017
  • ASCO GU 2017: Best of Journals: Renal Cell Carcinoma – Urologic Oncology - Session Highlights

    Orlando, Florida USA (UroToday.com) In this session, Dr. Uzzo reviewed the important surgical literature in renal cell carcinoma (RCC) from 2016. A systematic review of the Agency for Healthcare and Research Quality demonstrated that renal mass biopsy (RMB) is a safe and important tool. Twenty studies comprising 2,797 patients and 3,113 RMBs were included in the meta-analysis. The non-diagnostic rate was 14% and repeat biopsies in these cases were diagnostic in 80%. The false positive rate was only 4%. Core biopsy sensitivity and specificity were 97.5% and 96.2% respectively. Accuracy regarding grade concordance varied from 56-76% and upgrading from low to high grade occurred in 16%. Adverse events occurred in 5-7% of patients with hematoma (4.9%) being the most common. One area of controversy in RMB is an oncocytic diagnosis. Fortunately, annual growth rates for oncocytic lesions are 0.2-0.4 cm/year. In one study, eight patients (total n = 95) elected surgery over a period of 24 months’ median follow-up and no patients died of RCC.

    Published February 18, 2017
  • ASCO GU 2017: Phase II Study Supports Potential For Genentech’s TECENTRIQ® (ATEZOLIZUMAB) PLUS AVASTIN® (BEVACIZUMAB) For People With Locally Advanced or Metastatic Renal Cell Carcinoma - Session Highlights

    • Proof-of-concept study in first-line mRCC (a type of kidney cancer) shows that TECENTRIQ and Avastin can be combined with a manageable safety profile
    • Study results also showed encouraging efficacy compared to sunitinib in those people whose disease expressed the PD-L1 (programmed death-ligand 1) protein
    • Genentech is evaluating TECENTRIQ plus Avastin in a Phase III study (IMmotion151) in people with previously untreated, locally advanced or metastatic RCC

    Orlando, Florida USA (UroToday.com) February 17, 2017 – Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced encouraging results from the Phase II IMmotion150 study that compared TECENTRIQ® (atezolizumab) plus Avastin® (bevacizumab) and TECENTRIQ monotherapy to sunitinib alone in people with previously untreated, locally advanced or metastatic renal cell carcinoma (mRCC). These results were presented at the 2017 Genitourinary Cancers Symposium taking place from February 16-18 in Orlando, Fla. IMmotion150 is the first randomized clinical trial to evaluate the combination of TECENTRIQ and Avastin in mRCC. The study was designed to inform further clinical development of this combination, and these study results reinforce the potential of this combination in this setting.

    Published February 18, 2017
  • ASCO GU 2018: IMmotion 151: A randomized Phase III Study of Atezolizumab Plus Bevacizumab versus Sunitinib in Untreated Metastatic Renal Cell Carcinoma

    San Francisco, CA (UroToday.com) Atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) have showed first line anti-tumor activity with an acceptable side effect profile in a Phase II study performed by Dr. McDermott, presented at GU ASCO 2017.  In this oral abstract session, Dr. Motzer presented the first phase III randomized clinical trial combining a PD-L1/PD-1 with an anti-VEGF agent in first line metastatic renal cell carcinoma. It was theorized that atezolizumab’s T cell mediated cancer cell killing may be enhanced through bevacizumab’s reversal of VEGF mediated immunosuppression.
    Published February 12, 2018
  • ASCO GU 2018: Incidence and mortality of Renal Cell Carcinoma in the U.S.: A SEER-based Study Investigating Trends Over the Last Four Decades

    San Francisco, CA (UroToday.com) Renal cell carcinoma (RCC) is the third most common urologic malignancy worldwide – due to increasing cross-sectional imaging, there have been prior studies demonstrating increasing incidence of RCC, particularly localized RCC. While there are many histologic subtypes, the majority of RCC’s present with clear cell subtype.
    Published February 13, 2018
  • ASCO GU 2018: Outcomes of Metastatic Chromophobe Renal Cell Carcinoma with Sarcomatoid Features

    San Francisco, CA (UroToday.com) Dr. Yasser Ged from Memorial Sloan Kettering Cancer Center (MSKCC) discussed their institution’s experience with metastatic chromophobe renal cell carcinoma with sarcomatoid features. Chromophobe RCC makes up 5-10% of RCC subtypes and is generally thought to confer favorable prognosis. However, presence of sarcomatoid features on histologic review can occur in any RCC subtype and is considered a hallmark of aggressive disease. The objective of this study was to assess outcomes in a cohort of patients with metastatic chromophobe RCC with sarcomatoid features.
    Published February 12, 2018
  • ASCO GU 2018: Phase III Trial of Adjuvant Sunitinib in Patients with High-risk Renal Cell Carcinoma: Exploratory Pharmacogenomic Analysis

    San Francisco, CA (UroToday.com) Dr. George presented data from a pharamacogenomic analysis of S-TRAC data (Phase III trial of adjuvant sunitinib for high-risk RCC). As a brief background, S-TRAC demonstrated a disease-free survival (DFS) benefit for patients who received adjuvant sunitinib after nephrectomy for high-risk RCC. This DFS rate appears to be durable beyond 5 years (see figure). This data is notably different than the outcome of the ASSURE trial, which may be due to the patient selection of mainly high-risk disease in S-TRAC. As a result of this data, the FDA recently approved sunitinib for adjuvant therapy in high-risk RCC.
    Published February 12, 2018
  • ASCO GU 2018: Status of Adjuvant Therapy in Renal Cell Carcinoma in 2018: Completed Trials and What Is Being Tested?

    San Francisco, CA (UroToday.com) Dr. Haas presented an overview of our current understanding of adjuvant VEGF TKIs in patients with high-risk renal cell carcinoma (RCC). This discussion is particularly pertinent in light of the recent FDA-approval of sunitinib for adjuvant treatment in patients with high risk RCC, which generated considerable controversy in the GU oncology world.
    Published February 11, 2018
  • ASCO GU 2018: The CLEAR study: A Phase 3 Trial to Compare Efficacy and Safety of Lenvatinib in Combination with Everolimus or Pembrolizumab Versus Sunitinib Alone in First-line Treatment of Patients with Metastatic Renal Cell Carcinoma

    San Francisco, CA (UroToday.com) Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptor 1–3, fibroblast growth factor receptor 1–4, platelet-derived growth factor receptor alpha, and RET and KIT. Based on a phase 2 study,1 LEN was approved in combination with everolimus (EVE) for the treatment of metastatic renal cell carcinoma (RCC) following 1 prior VEGF-targeted therapy. A phase 1b/2 study of LEN in combination with pembrolizumab (PEM) in patients (pts) with RCC is also underway.
    Published February 14, 2018
  • ASCO GU 2018: The Future of Immuno-Oncology in Renal Cell Carcinoma

    San Francisco, CA (UroToday.com) Dr. Bernard Escudier provided one of the Keynote Lectures for kidney cancer at the GU ASCO 2018 meeting, discussing the future of immuno-oncology in renal cell carcinoma (RCC). The current landscape of immune-oncology essentially started with the phase III randomized clinical trial (RCT) CheckMate 025 assessing nivolumab (n=410) vs everolimus (n=411) in the setting of previously treated RCC, demonstrating a statistically significant OS benefit for nivolumab (median OS 25.0 vs 19.6; HR 0.73, 95%CI 0.57-0.93) [1]. In addition to this survival benefit, patients receiving nivolumab had a superior quality of life compared to patients randomized to everolimus. This RCT ultimately cemented nivolumab as the standard of care in mRCC as second-line treatment after failure of VEGF targeted agents. 
    Published February 12, 2018
  • ASCO GU 2018: Tyrosine Kinase Inhibitors for Renal Cell Carcinoma: Past, Present, and Future

    San Francisco, CA (UroToday.com) Dr. Robert Motzer from Memorial Sloan Kettering Cancer Center provided one of the kidney cancer Keynote Lectures at the 2018 GU ASCO meeting in San Francisco. Currently there are 10 FDA-approved drugs for advanced/metastatic RCC since 2005, and we have certainly seen an improved survival with the targeted therapies:
    Published February 12, 2018
  • ASCO GU 2019: Pembrolizumab Plus Axitinib versus Sunitinib as First-line Therapy for Locally Advanced or Metastatic Renal Cell Carcinoma: Phase III KEYNOTE-426 Study

    San Francisco, CA (UroToday.com) Previous data has demonstrated that pembrolizumab (anti PD-L1 monoclonal antibody) and axitinib (VEGFR-TKI) have antitumor activity as monotherapies in the advanced RCC setting.  It is hypothesized that these two medications may have synergistic effects, and this is supported by a phase 1b study, where pembrolizumab plus axitinib demonstrated a high overall response rate promising progression free survival and a tolerable safety profile. 
    Published February 18, 2019
  • ASCO GU 2019: Phase Ib (COSMIC-021) Trial of Cabozantinib in Urothelial Carcinoma or Cabozantinib in Combination with Atezolizumab in patients with Urothelial Carcinoma, Castrate Resistant Prostate Cancer or Renal Cell Carcinoma

    San Francisco, CA (UroToday.com) Cabozantinib is a VEGFR2/MET/AXL tyrosine kinase inhibitor with anti-angiogenic, anti-tumor growth and immune regulation properties. Recent studies have demonstrated that cabozantinib may enhance response to immune checkpoint inhibitors (ICI) such as PD-1 and PD-L-1 inhibitors. It is currently approved for patients with advanced or metastatic RCC (mRCC) and has been used in combination therapies for the treatment of renal cell carcinoma (RCC), urothelial carcinoma (UC), and castrate-resistant prostate cancer (CRPC).
    Published February 18, 2019
  • ASCO GU 2019: Subgroup Analysis from JAVELIN Renal 101: Outcomes for Avelumab plus Axitinib versus Sunitinib in Advanced Renal Cell Carcinoma

    San Francisco, CA (UroToday.com) In this podium presentation, Dr. Choueiri explained that avelumab, an anti PD-L1 monoclonal antibody and axitinib, a VEGF tyrosine kinase inhibitor, have demonstrated activity as monotherapy for advanced renal cell carcinomas (aRCC).  In a previous phase 1b trial, combination avelumab + axitinib therapy had an objective response rate of 68% and a favorable safety profile in a phase 1b study.  Furthermore, previous data also demonstrated improved progression-free survival and objective response rate (13.8 vs 8.4 mo, HR 0.69, p=0.0001; 51% vs 26% with avelumab + axitinib compared to sunitinib in patients with previously untreated advanced renal cell carcinoma (aRCC).
    Published February 18, 2019
  • AUA 2018: Effect of African-American Race on Cancer Specific Mortality Differs According to Clear-Cell vs Non-Clear Cell Histologic Subtype in Metastatic Renal Cell Carcinoma

    San Francisco, CA (UroToday.com) The potential effect of race (African-American vs. Caucasian), was never examined in the setting of cancer specific mortality (CSM) in clear cell vs. non-clear cell metastatic renal cell carcinoma (ccmRCC vs. non-ccmRCC). The authors presented a study assessing the impact of race on these outcomes. 
    Published May 24, 2018
  • AUA 2018: Effect of Ketogenic Diet on the Clear Cell Renal Cell Carcinoma Cell Growth

    San Francisco, CA USA (UroToday.com) In recent years, lifestyle intervention via diet and exercise has become an increasingly popular prevention and therapy mechanism for patients suffering from diseases known to be exacerbated by metabolic syndromes. In this regard, clear cell renal cell carcinoma (ccRCC) has been of no exception.
    Published May 29, 2018
  • 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
  • CUOS 2019: Cytoreductive Nephrectomy: Is There Still a Role for Nephrectomy in Patients with Metastatic RCC?

    Toronto, Ontario (UroToday.com) There were an estimated 6600 new cases of kidney cancer in Canada in 2018, with a 1/3 of them presenting with regional or distant metastases. According to the European Association of Urology (EAU) guidelines, there is a weak recommendation to perform cytoreductive nephrectomy in favorable and intermediate risk patients with metastatic renal cell carcinoma (RCC). For patients with oligometastatic disease, the guidelines recommend performing immediate cytoreductive nephrectomy if complete resection could be achieved. The recommendations of the National Comprehensive Cancer Network (NCCN) guidelines are quite similar.
    Published January 13, 2019
  • EAU 2018: Surgical Safety of Immediate versus Deferred Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Renal Cell Carcinoma - SURTIME

    Copenhagen, Denmark (UroToday.com) Targeted therapy, including mTOR-inhibitors and tyrosine-kinase inhibitors, have drastically changed the landscape of the management of advanced renal cell carcinoma. Cytoreductive nephrectomy (CN) in the pre-targeted therapy era was the standard, but recent evidence suggests that a period of targeted therapy prior to CN may be an effective alternative approach to immediate CN. 
    Published March 16, 2018
  • ESMO 2017: A Change of Paradigm in First-Line Treatment of Metastatic Renal Cell Carcinoma?

    Madrid, Spain (UroToday.com) Dr. Manuela Schmidinger provided an excellent discussant commentary for the late-breaking abstract “CheckMate 214: Efficacy and safety of Nivolumab + Ipilimumab vs Sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups” [1] presented by Dr. Escudier and colleagues. As. Dr. Schmidinger notes, for more than a decade now, VEGF-inhibitors have been first-line agents for patients with favorable or intermediate risk clear cell mRCC.
    Published September 11, 2017
  • ESMO 2017: KEYNOTE-564: Phase 3 trial of pembrolizumab in the adjuvant treatment of renal cell carcinoma

    Madrid, Spain (UroToday.com) Dr. Choueiri and colleagues presented their phase III trial design of adjuvant pembrolizumab for patients with renal cell carcinoma (RCC). Effective adjuvant therapies for patients with RCC at risk of recurrence after nephrectomy are lacking, and previous adjuvant therapy trials utilizing TKIs have proven disappointing [1-3].
    Published September 11, 2017
  • ESMO 2018: Avelumab + Axitinib vs Sunitinib for the Management of Advanced Renal Cell Carcinoma - JAVELIN Renal 101

    Munich, Germany (UroToday.com) Dr. Motzer, on behalf of the JAVELIN clinical trial group, presents the results of the first study to combine a targeted therapy and immune checkpoint inhibitor for the management of advanced renal cell carcinoma (aRCC).
    Published October 22, 2018
  • ESMO 2018: COSMIC-021, Phase Ib Study of Cabozantinib in Combination with Atezolizumab and Potent Natural Killer, Myeloid Blood Cell Remodeling by Cabozantinib

    Munich, Germany ( UroToday.com) Cabozantinib is a multikinase inhibitor of MET, VEGFR, AXL and RET1. In the sphere of metastatic renal cell carcinoma, cabozantinib is currently being used in both first line and second line therapy, based on CABOSUN for first line and METEOR for second line2,3.  In addition to being a tyrosine kinase inhibitor, there is some evidence that cabozantinib may alter the tumor immune microenvironment, altering regulatory T cells (Tregs) as well as myeloid-derived suppressor cells (MDSC)4.
    Published October 22, 2018
  • ESMO 2018: Immunotherapy in Renal and Bladder Cancers

    Munich, Germany (UroToday.com) Cora Sternberg, MD gave an overview of the contemporary role of immunotherapy in renal and bladder cancer. Immunotherapy in renal cancer began with the introduction of high dose IL-2 therapy in a total of 7 clinical trials including 255 patients.1 IL-2 was FDA approved in 1992 demonstrating 15% risk reduction with durable responses in a small percentage of patients. However, this treatment caused significant toxicity and had considerable cost.

    Published October 20, 2018
  • ESMO 2018: JAVELIN Renal 101: A Randomized, Phase 3 Study of Avelumab + Axitinib vs Sunitinib as First-Line Treatment of Advanced Renal Cell Carcinoma

    Munich, Germany (UroToday.com) Frontline therapy for advanced renal cell carcinoma (RCC) has rapidly evolved over the past decade, with the addition of several new vascular endothelial growth factor (VEGF)-directed agents as well as immune checkpoint inhibitors. For patients with intermediate or high-risk disease, cabozantinib and combination ipilimumab+nivolumab have emerged as preferred frontline options based on data from CABOSUN and Checkmate 2141,2.
    Published October 21, 2018
  • ESMO 2018: Molecular Correlates Differentiate Response to Atezolizumab plus Bevacizumab vs Sunitinib: Results From a Phase III Study IMmotion151 in Untreated mRCC

    Munich, Germany (UroToday.com) In this abstract, the authors of ImMotion151, which assesses the immune checkpoint combination of atezolizumab and prior immunotherapy bevacizumab against the traditional standard of sunitinib for patients with untreated metastatic renal cell carcinoma (mRCC), focus on the molecular correlates utilized and their preliminary results. InMotion151 is a phase III study and has previously reported at ASCO – it was first randomized Phase III trial of a PD-L1/PD-1 pathway inhibitor combined with an anti-VEGF agent in 1L mRCC. In the primary results, the median PFS HR for atezo + bev (AB) vs sunitinib (SUN) was 0.74 (95% CI 0.57, 0.96) in PD-L1+ pts and 0.83 (95% CI 0.70, 0.97) in ITT pts.
    Published October 20, 2018
  • ESMO 2018: PD-L1 Status and Clinical Outcomes to Cabozantinib, Sunitinib and Everolimus in Patients with Metastatic Clear-Cell RCC Treated on CABOSUN and METEOR Trials

    Munich, Germany (UroToday.com) Cabozantinib, a multiple receptor tyrosine kinase inhibitor (RTK) that inhibits c-Met, VEGFR2, AXL, and RET, is an agent that has now been established in 2 separate randomized controlled trials as effective 2nd line therapy for metastatic RCC (METEOR trial, Choueiri NEJM 2015) and as 1st line therapy for intermediate/poor risk mRCC patients (CABOSUN trial, Choueiri NEJM 2017). In METEOR, it had a 5-month median OS benefit compared to everolimus, while in CABOSUN it demonstrated a 3-month median PFS benefit in poor/intermediate risk patients compared to sunitinib.
    Published October 20, 2018
  • ESMO 2018: The Current Use of TKI in Renal Cancer

    Munich, Germany (UroToday.com) Dr. Gizzi gave a talk on the role of Tyrosine Kinase Inhibitors (TKI) in renal cell carcinoma (RCC).   Hypoxia-inducible factor (HIF) is a heterodimeric transcriptional factor composed of a constitutively expressed β subunit and an oxygen-regulated α subunit. HIF is detrimental in glucose metabolism regulation, angiogenesis, and erythropoiesis under oxygen-limited conditions.
    Published October 21, 2018
  • ESMO 2018: The Role of PD-L1 Status as A Predictor or Prognostic Marker of Clinical Outcomes in Patients Treated on CABOSUN and METEOR

    Munich, Germany (UroToday.com) METEOR was a phase 3, open-label, randomized controlled trial which compared the efficacy of cabozantinib to everolimus, for patients with mRCC who had progressed after VEGFR-targeted therapy1. In this study, 658 patients were randomized to either receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily and the primary endpoint was progression free survival (PFS). This study found that median PFS was 7.4 months with cabozantinib and 3.8 months with everolimus, which established cabozantinib as a reasonable second-line therapy for patients with mRCC.
    Published October 20, 2018
  • ESOU 2019: Cytoreductive Nephrectomy: What are the Current Recommendations?

    Prague, Czech Republic (UroToday.com) Dr. Arnaud Méjean, the primary investigator and senior author the CARMENA study, was invited to review the current recommendations for cytoreductive nephrectomy. He had first presented the CARMENA results at ASCO 2018.
    Published January 20, 2019
  • ESOU 2019: Revolution in the First Line Treatment for Metastatic Renal Cell Carcinoma: Where Do We Stand?

    Prague, Czech Republic (UroToday.com)  Dr. Peter Mulders presented at the close of the renal cell carcinoma section, focusing on metastatic renal cell carcinoma patients. He provided a review of the literature and some thoughts for the future.
    Published January 20, 2019
  • Everolimus versus Sunitinib for Patients with Metastatic Non-clear Cell Renal Cell Carcinoma (ASPEN): a Multicentre, Open-label, Randomised Phase 2 Trial

    BACKGROUND: Non-clear cell renal cell carcinomas are histologically and genetically diverse kidney cancers with variable prognoses and their optimum initial treatment are unknown. We aimed to compare the mTOR inhibitor everolimus and the VEGF receptor inhibitor sunitinib in patients with non-clear cell renal cell carcinoma. 
    Published December 3, 2018
  • Exelixis’ Partner Ipsen Announces Health Canada’s Approval of Cabozantinib Tablets for the Treatment of Adults with Previously Treated Advanced Renal Cell Carcinoma

    – Approval based on the improvement in overall survival, progression-free survival and objective response rate for cabozantinib versus everolimus in the phase 3 pivotal METEOR trial –

    San Francisco, CA (UroToday.com) -- Exelixis, Inc. announced that its partner Ipsen Biopharmaceuticals Canada Inc. received approval from Health Canada of CABOMETYX® (cabozantinib) tablets for the treatment of adults with advanced renal cell carcinoma (RCC) who have received prior vascular endothelial growth factor (VEGF) targeted therapy. Health Canada granted CABOMETYX priority review status, which provided an accelerated review of Ipsen’s new drug submission.
    Published September 19, 2018

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