Evidence and experience for the management of metastatic renal cell carcinoma

Aims and scope The last 7 years have seen the treatment landscape for metastatic renal cell carcinoma (mRCC) dramatically change as the understanding of the molecular background of the disease has grown. With the increase in treatment options, however, comes the question of how best to maximise patient benefits based on the available medicines. This topic was the key focus of a Pfizer meeting held at the 8th European International Kidney Cancer Symposium (EIKCS) in Budapest, Hungary (3–4 May 2013), where leading oncology experts reviewed the latest clinical trial evidence and discussed the importance of real world experience in treating patients with mRCC. This report offers an overview of the discussion on how best to integrate clinical trial data, guideline recommendations and real world experience in order to make treatment decisions that will provide the maximum benefit for each individual patient

mRCC management: past, present and future

Aims and scope Over the last six years, the use of targeted agents has revolutionised the treatment of metastatic renal cell carcinoma (mRCC) and dramatically improved outcomes for patients. Multiple effective first-and second-line agents are now available or are in development, raising key questions and new challenges around the long-term management of mRCC. These topics were the focus of a Pfizer meeting held at the 7 th European International Kidney Cancer Symposium (EIKCS) in Vienna (4–5 May 2012), where leading European oncology experts discussed recent advances and ongoing issues in mRCC clinical practice. 'It is important for clinicians who see large numbers of patients with this rare disease to get together and share their experience and observations, for the benefit of those who only see few patients in their practice', said Professor Manuela Schmidinger, Chair of the meeting. This report offers an overview of the critical evidence and the issues of long-term mRCC management debated at the meeting. It also presents key conclusions from the recently launched report 'Europe 2012: is kidney cancer management at a crossroad?', written by a selected panel of European kidney cancer experts to highlight current barriers to the optimal treatment of mRCC patients and the development of solutions to address these

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy

Renal cell carcinoma; Immune checkpoint inhibitor; MetastaticCarcinoma de células renales; Inhibidor del punto de control inmunitario; MetastásicoCarcinoma de cèl·lules renals; Inhibidor del punt de control immunitari; MetastàticThe first-in-class, small molecule HIF-2α inhibitor, belzutifan, has demonstrated promising antitumor activity in previously treated patients with clear cell renal cell carcinoma (RCC). HIF-2α also regulates VEGF expression and is involved in resistance to anti-VEGF therapy. This study describes the rationale and design for a randomized, phase III study evaluating efficacy and safety of belzutifan plus the tyrosine kinase inhibitor (TKI) lenvatinib versus the TKI cabozantinib in patients with advanced RCC progressing after anti-PD-1/PD-L1 therapy in the first- or second-line setting or as adjuvant therapy. Considering the unmet need for effective and tolerable treatment of advanced RCC following immune checkpoint inhibitors, belzutifan plus lenvatinib may have a positive benefit/risk profile

real world experience with sunitinib treatment in patients with metastatic renal cell carcinoma clinical outcome according to risk score

Abstract Background ADONIS is an ongoing observational study in 9 European countries, designed to evaluate treatment patterns/outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line sunitinib and/or second-line axitinib post sunitinib. We present an evaluation of sunitinib efficacy by risk group, in the real-world setting examined in ADONIS. Methods Patients were enrolled at the start of first-line sunitinib treatment or second-line axitinib post sunitinib treatment. Evaluation of sunitinib efficacy was assessed by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center risk criteria. Results For all patients in this analysis (N = 467), median progression-free survival was 23.8 (95% CI 16.5-28.5), 11.8 (8.1-17.4), and 4.6 (2.5-7.7) months for IMDC favorable-, intermediate-, and poor-risk groups, respectively. Median overall survival was 97.1 (46.3-not evaluable [NE]), 33.5 (20.5-46.6), and 10.0 (4.5-19.8) months for the respective risk groups. Data on individual risk factors were available for a subgroup of patients, allowing analysis by intermediate risk by 1 versus 2 risk factors. When including this subgroup (n = 120), median overall survival for IMDC favorable-, intermediate-1, and intermediate-2 risk factors was 21.6 (16.3-NE), 20.5 (15.5-NE), and 15.1 (4.1-NE) months, respectively. Conclusions For patients overall and by risk-group stratification, survival estimates were aligned with improvements in clinical practice over the past decade. In patients with intermediate-1 risk, overall survival was very similar to patients with favorable risk. However, further exploration is needed to confirm these observations. ClinicalTrials.gov identifier: NCT0218441

Impact of COVID-19 pandemic on treatment patterns in metastatic clear cell renal cell carcinoma.

BACKGROUND: The coronavirus pandemic has provoked discussions among healthcare providers how to manage cancer patients when faced with the threat of severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) infection. Immune checkpoint inhibitor (ICI) containing regimens are standard of care in the majority of metastatic clear cell renal cell carcinoma (mccRCC) patients. It remains unclear whether therapies should be modified in response to the COVID-19 pandemic. METHODS: We performed an online survey among physicians involved in the treatment of mccRCC, and 41 experts responded. Questions focused on criteria relevant for treatment decision outside the pandemic and the modifications of systemic therapy during COVID-19. FINDINGS: For the majority of experts (73%), the combination of International metastatic renal cell carcinoma Database Consortium (IMDC) risk category and patient fitness are two important factors for decision-making. The main treatment choice in fit, favourable risk patients outside the pandemic is pembrolizumab/axitinib for 53%, avelumab/axitinib, sunitinib or pazopanib for 13% of experts each. During the pandemic, ICI-containing regimens are chosen less often in favour of a tyrosine kinase inhibitors (TKI) monotherapy, mainly sunitinib or pazopanib (35%).In fit, intermediate/poor-risk patients outside the pandemic, over 80% of experts choose ipilimumab/nivolumab, in contrast to only 41% of physicians during COVID-19, instead more TKI monotherapies are given. In patients responding to established therapies with ICI/ICI or ICI/TKI combinations, most participants modify treatment regimen by extending cycle length, holding one ICI or even both. CONCLUSION: mccRCC treatment modifications in light of the coronavirus pandemic are variable, with a shift from ICI/ICI to ICI/TKI or TKI monotherapy

Real-world Effectiveness and Safety of Pazopanib in Patients With Intermediate Prognostic Risk Advanced Renal Cell Carcinoma

Patients with intermediate-risk advanced renal cell carcinoma are a heterogeneous population, having either 1 or 2 risk factors. It is unclear whether all patients in this risk category should be treated similarly. A secondary analysis of the PRINCIPAL study of pazopanib found that patients can be stratified by number of risk factors and Eastern Cooperative Oncology Group performance status to more accurately predict outcomes. Introduction: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). Patients and Methods: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. Results: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS >= 2 (vs. PS = 2) to more accurately predict outcomes. (C) 2019 Published by Elsevier Inc.Peer reviewe

Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents.</p> <p>Methods</p> <p>Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment.</p> <p>Results</p> <p>Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034).</p> <p>Conclusions</p> <p>Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM.</p

Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

BACKGROUND: In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib. METHODS: We randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety. RESULTS: A total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P&lt;0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P&lt;0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups. CONCLUSIONS: Progression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.)