ASCO GU 2019 Kidney Cancer

ASCO GU 2019 Kidney Cancer

ASCO GU 2019: Results from KEYNOTE-427 Cohort B: First-line Pembrolizumab Monotherapy for Advanced Non-Clear Cell Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Non-clear cell renal cell carcinoma represents up to 25% of patients with renal cell carcinoma.1 The majority of patients will have papillary RCC (15%) or chromophobe (5%), but several other types exist including collecting duct carcinoma, medullary carcinoma, translocation, and unclassified RCC.  

ASCO GU 2019: Phase III CheckMate 214 Trial of First-Line Nivolumab + Ipilimumab or Sunitinib in Patients with Advanced Renal Cell Carcinoma with Thirty Month Follow Up Results

San Francisco, CA (UroToday.com) Checkmate 214 revolutionized front-line treatment of patients with intermediate or poor risk metastatic renal cell carcinoma (mRCC) by introducing combination immunotherapy ipilimumab and nivolumab.  In the original New England Journal of Medicine publication in 2018, at a median follow up of 25.2 months, the 18-month overall survival was 75% with ipi/nivo compared with 60% with sunitinib for patients with intermediate or poor risk features, and the objective response rate was 42% vs 27% (p<0.001) with an impressive 9% complete response rate,1 which led to FDA approval of ipi/nivo in April 2018 and EMA approval in 11/2018. This abstract provides an update to the original data with 30 month follow up results. 

ASCO GU 2019: Final analysis from the NIVOREN GETUG AFU 26 study — Safety and Efficacy of Nivolumab in Metastatic Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Immune checkpoint inhibitors have changed the treatment paradigm of metastatic renal cell carcinoma (mRCC), both in the front line and second line settings. Nivolumab, a humanized IgG4 anti-PD-L1 monoclonal antibody, is approved in both settings, based on CheckMate 214 (in combination with ipilimumab) in the first line, and CheckMate 025 in the second line.1,2

ASCO GU 2019: Phase III KEYNOTE-426 Study: Pembrolizumab plus Axitinib versus Sunitinib as First-Line Therapy for Locally Advanced or Metastatic Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Combination vascular endothelial growth factor (VEGF) inhibition with immunotherapy has shown promising results in several phase I/II studies. During ASCO 2018, Dr. Lee et al presented a study of 30 patients with metastatic renal cell carcinoma (mRCC) who were treated with Pembrolizumab and Levantinib, and this combination yielded an overall response rate of 66.7% by RECIST v1.1 and irRECIST with a median duration of response of 18.4 months.1 97% of patients experienced some tumor size reduction from baseline. A phase II study of Avelumab plus axitinib was presented at 2017 ASCO and this combination achieved an ORR of 58.20%.2 Preliminary data regarding the combination of pembrolizumab and axitinib was initially presented at GU ASCO 2018, and out of 52 patients, 73.1% of patients had an objective response with a median PFS of 20.9 months.3 This abstract provides the phase III update to that data.

ASCO GU 2019: A Phase II Study CALYPSO: The Safety and Efficacy of Savolitinib and Durvalumab in Metastatic Papillary Renal Cancer

San Francisco, CA (UroToday.com) The most common non-clear cell renal cell carcinoma is papillary renal cell carcinoma (pRCC). pRCC accounts for 15-20% of RCC and are subcategorized into Type 1 and Type 2. Type 1 pRCC are typically associated with MET alterations whereas Type 2 pRCC typically are found to have alterations in SETD2, TFE3, and CDKN2A.1

ASCO GU 2019: Outcomes of Patients with Metastatic Clear Cell RCC Treated with Second Line VEGFR-TKI After First Line Immune Checkpoint Inhibitor

San Francisco, CA (UroToday.com) Since the publication of CheckMate 214, immune checkpoint inhibitors (ICIs) have entered the first line space for the treatment of metastatic RCC1. However, the majority of patients do not have an objective response to ICI and will have either primary or secondary resistance. Standard of care second line therapies involves VEGFR-TKIs, but little is known about their efficacy after ICI treatment.  This study seeks to address this knowledge gap by providing a multicenter experience of treatment of mRCC after ICI therapy.

ASCO GU 2019: Questions and Lessons Moving Forward from CARMENA: Which Treatment First? Surgeon’s Perspective

San Francisco, CA (UroToday.com) Dr. Russo gave the surgeon’s perspective of cytoreductive nephrectomy.  The role and rationale for cytoreductive nephrectomy (CN) is multi-fold:

  • Remove a large, potentially immunosuppressive tumor that is a potential source of metastases and paraneoplastic syndromes
  • Palliate local symptoms of pain or bleeding that could complicate/interrupt systemic therapy
  • Obtain accurate pathologic subtyping to guide therapy
  • Should never be done to induce spontaneous metastatic tumor regression (it is a real event, but rare)

ASCO GU 2019: Questions and Lessons Moving Forward from CARMENA: Which Treatment First? Medical Oncologist’s Perspective

San Francisco, CA (UroToday.com) Dr. Harshman gave the Medical Oncologist perspective of cytoreductive nephrectomy (CN) . As has been the case for many of these debates recently, there wasn’t much of a debate – both medical oncologists and urologists have been on the same page!

ASCO GU 2019: Informing the Decision Using Data Science

San Francisco, CA (UroToday.com) In this first talk of the point-counterpoint session, Dr. Psutka reviews the literature informing the decision to expand the use of partial nephrectomy to larger, more complex masses, effectively titled “extended partial nephrectomy” (ePN).

To begin, the only Level 1 evidence supporting the oncologic efficacy PN compared to RN is the EORTC study by van Poppel et al. (EU 2007). However, it was underpowered and had significant cross-over. 

ASCO GU 2019: Quality Metrics in Kidney Cancer Care

San Francisco, CA (UroToday.com) The last session of GU ASCO 2019, How Can We Better Treat Kidney Cancer, started with Dr. John Gore presented quality metrics in kidney cancer care. Dr. Gore notes that quality measurement entails several processes, including effectiveness, efficacy, equity, patient-centeredness, safety, and timeliness. Dr. Gore then mentioned that health care value is disparate in the United States, considering that the country has the highest per-capita spending per person for health care ($9,892), but is 27th in life expectancy (78.8 years). By comparison, Japan is 15th in spending ($4,519) and 1st in life expectancy (83.9 years).

ASCO GU 2019: Outcomes for Avelumab Plus Axitinib versus Sunitinib in Advanced RCC - JAVELIN Renal 101: A Subgroup Analysis

San Francisco, CA (UroToday.com) The first line treatment for mRCC disease space is rapidly changing, including the first reporting of JAVELIN Renal 101 at ESMO 2018 comparing avelumab plus axitinib versus sunitinib. Highlights of this first analysis included a longer progression-free survival (PFS) (median, 13.8 vs 8.4 months; HR 0.69; p=0.0001) and better objective response rate (ORR) (51% vs 26%) for combination avelumab plus axitinib versus sunitinib in patients with previously untreated advanced/metastatic RCC.

ASCO GU 2019: Kidney Cancer Case-Based Panel: Localized Disease

San Francisco, CA (UroToday.com) The case-based discussion of kidney cancer patients featured a multi-disciplinary team including urologists, medical oncologists, and interventional radiologists.  Dr. Peter Clark chaired the localized kidney cancer panel, presenting several cases from his practice for discussion.

ASCO GU 2019: When to Obtain Genetic Testing for Syndromic Renal Cell Cancer

San Francisco, CA (UroToday.com) Dr. Brian Shuch provides a summary and guide to genetic testing for syndromic renal cell carcinoma (RCC).  There is an established strong inheritance pattern in kidney cancer, and now there are 15+ recognized monogenic (single-gene related) syndromes (seen in the list below). More importantly, there are complex inheritance patterns due to SNPs in patients without monogenic syndromes.

ASCO GU 2019: Phase II Trial of Nivolumab Plus Ipilimumab in Patients with SMARCB1 Deficient Kidney Malignancies

San Francisco, CA (UroToday.com) Last year, CheckMate 214 reported a significant overall survival (OS) benefit for intermediate and poor risk mRCC patients with combination nivolumab plus ipilimumab vs sunitinib1.  Given these encouraging outcomes, the search for additional applications of this combination therapy is ongoing. The potent tumor suppressor SMARCB1 (also known as INI-1, hSNF5, or BAF47) is inactivated in all cases of renal medullary carcinoma and renal cell carcinoma unclassified with medullary phenotype, as well as most malignant rhabdoid tumors of the kidney. 

ASCO GU 2019: TIVO-3: A Phase III, Randomized, Controlled, Multicenter, Open-label Study to Compare Tivozanib to Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Tivozanib is a selective oral VEGFR 1, 2, and 3 tyrosine kinase inhibitor which has been studied in numerous solid tumors including hepatocellular carcinoma, recurrent glioblastoma, and soft tissue sarcoma1-3. Tivozanib has also been studied in the first line setting for metastatic RCC in a large phase III trial with 517 patients, randomly assigned to tivozanib or sorafenib4.  

ASCO GU 2019: JAVELIN Renal 101: Outcomes for Avelumab + Axitinib vs Sunitinib in Advanced Renal Cell Carcinoma (RCC)

San Francisco, CA (UroToday.com) While immunotherapy has entered both the first- and second-line treatment options for patients with metastatic renal cell carcinoma, the majority of patients do not have an objective response to single agent immunotherapy. Even with dual checkpoint inhibition as demonstrated in CheckMate 214, 58% of patients did not have an objective response1. Thus, several combination therapies are now being evaluated in this space, combining checkpoint inhibition with VEGF/VEGFR inhibition. JAVELIN Renal 101 is a global phase III study of avelumab plus axitinib versus sunitinib alone. During ASCO 2017, results from the avelumab + axitinib phase 1b study demonstrated that 58% of patients had an objective response (5% complete response, 53% partial response), and 45 out of 53 patients experienced tumor shrinkage2. This abstract provides the subgroup analysis of JAVELIN 101.

ASCO GU 2019: Multidisciplinary Tumor Board: Case-Based Discussion on Kidney Cancer

San Francisco, CA (UroToday.com) Dr. Toni Choueiri chaired the advanced/metastatic kidney cancer panel, presenting a case from his practice for discussion. This patient was a 63-year-old female with a 3-month history of bloating, malaise, weight loss, inability to concentrate, and intermittent gross hematuria. Her medical history was significant for hypertension, arthritis, and CAD. Pertinent medications included 325 mg aspirin and methotrexate and her images are as follows demonstrating an infiltrative right renal mass with peri-aortic lymphadenopathy.

ASCO GU 2019: Efficacy and safety of Nivolumab on Patients with Non-Clear Cell Renal Cell Carcinoma: Results from the Phase IIIb/IV CheckMate 374 Study

San Francisco, CA (UroToday.com) Nivolumab monotherapy is approved for the treatment of patients with advanced renal cell carcinoma (aRCC) who received prior antiangiogenic therapy. In the phase 3 Checkmate 025 trial in patients with previously treated aRCC, Nivolumab monotherapy demonstrated higher objective response rate and superior overall survival compared to everolimus (HR 0.79, p=0.002), with a lower incidence of treatment-relatedgrade 3-4 adverse events (19% vs. 37%).

ASCO GU 2019: Results from KEYNOTE-427 Cohort Bb - First-line Pembrolizumab Monotherapy for Advanced Non-Clear Cell RCC

San Francisco, CA (UroToday.com) Most renal cell carcinoma (RCC) histology is clear cell (80%), however clinical trial data for non-ccRCC are limited as many of these patients are often excluded from clinical trials. Therapies specifically approved by the FDA for advanced non-ccRCC are lacking, resulting in a substantial unmet need for safe and effective treatment options. PD-1/L1 pathway inhibitors are effective in clear cell RCC, but efficacy of PD-1 inhibitors (or any therapy) in non-ccRCC has not been established. KEYNOTE-427 is a single-arm, open-label, phase 2 study of pembrolizumab monotherapy in patients with advanced ccRCC (cohort A) and non-ccRCC (cohort B).

ASCO GU 2019: Final Analysis from the NIVOREN GETUG AFU 26 Study

San Francisco, CA (UroToday.com) The final presentation of GU ASCO 2019 featured Dr. Laurence Albiges presenting results from the final analysis of the NIVOREN GETUG AFU 26 study. This was a French multicenter prospective study to evaluate the safety and efficacy of nivolumab in a broad “real world setting” in mRCC after failure of 1 or 2 tyrosine kinase inhibitors.