Incidence and Outcomes of Delayed Targeted Therapy After Cytoreductive Nephrectomy for Metastatic Renal-Cell Carcinoma: A Nationwide Cancer Registry Study

Background

The optimal timing of targeted therapy (TT) initiation for metastatic renal-cell carcinoma (mRCC) is not clear. We used a nationwide cancer registry to determine clinical and social factors associated with delayed TT and to evaluate the association of a delayed approach with overall survival (OS).

Pattern of Care Study in Metastatic Renal-Cell Carcinoma in the Preimmunotherapy Era in Switzerland

Introduction

In metastatic renal-cell carcinoma (mRCC), physicians have a plethora of therapeutic choices, with the latest addition of checkpoint inhibitors. However, many questions regarding the best use of the respective drugs remain unanswered. Therefore, it is important to examine and summarize the outcome of real-world experiences to understand the practical value of the various drugs in daily use and foster optimal treatment algorithms for patients with renal-cell carcinoma. We sought to describe the pattern of care in mRCC under circumstances with access to all therapeutic options for patients.

Predictors of Long-Term Response With Pazopanib in Patients With Advanced Renal-Cell Carcinoma

Background

Pazopanib is among the current standards of care for first-line treatment of patients with unresectable advanced renal-cell carcinoma (aRCC) or metastatic renal-cell carcinoma. This real-world study aimed to characterize those with long-term response to pazopanib in the treatment of aRCC in a community oncology setting, and to identify predictors of long-term response.

Drug Holiday in Metastatic Renal-Cell Carcinoma Patients Treated With Vascular Endothelial Growth Factor Receptor Inhibitors

Introduction

Tyrosine kinase inhibitor (TKI) therapy in metastatic renal-cell carcinoma (mRCC) is noncurative and may be associated with significant toxicities. Some patients may receive treatment breaks as a result of TKI-related adverse effects or planned drug holidays.

Adjuvant Therapies in Nonmetastatic Renal-Cell Carcinoma: A Review of the Literature

To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer. The ClinicalTrials.gov website was queried to identify ongoing trials. Traditional adjuvant therapy agents consisted of interferon α, interleukin 2, autologous tumor cell vaccines, and monoclonal antibodies. None provided survival benefit. Three contemporary studies (S-TRAC, ASSURE, and PROTECT) using targeted therapy compared sunitinib to placebo (S-TRAC), sunitinib or sorafenib to placebo (ASSURE), and pazopanib to placebo (PROTECT), with controversial results. In contrast to ASSURE and PROTECT, S-TRAC demonstrated improved disease-free survival. Several trials that use checkpoint immunotherapy agents or vascular endothelial growth factor receptor tyrosine kinase inhibitors are ongoing. Many traditional therapies have shown no success as adjuvant therapy for nmRCC after nephrectomy. Targeted adjuvant therapy for nmRCC after nephrectomy showed controversial results, and its routine use is not currently endorsed.     

Factors Influencing Overall Survival for Patients With Metastatic Clear-Cell Renal-Cell Carcinoma in Daily Practice

Purpose

To describe factors associated with overall survival (OS) among patients with metastatic clear-cell renal-cell carcinoma (mccRCC) in regard to evolution of systemic therapies.

Sunitinib in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to International Metastatic Renal Cell Carcinoma Database Consortium Risk Group

Background

Sunitinib malate, a targeted tyrosine kinase inhibitor, is standard of care for metastatic renal cell carcinoma (mRCC) and serves as the active comparator in several ongoing mRCC clinical trials. In this analysis we report benchmarks for clinical outcomes on the basis of International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups for patients treated with sunitinib for mRCC in a first-line setting.

Neoadjuvant Cabozantinib in Renal-Cell Carcinoma: A Brief Review

Nephrectomy is the reference-standard treatment for renal-cell carcinoma (RCC). For patients with unresectable disease, tumor may be shrunk by using chemotherapy, thereby permitting surgical resection, which can be curative. We provided neoadjuvant cabozantinib, the preferred tyrosine kinase inhibitor for advanced RCC of poor and intermediate risk, to two patients with initially unresectable RCCs. In both patients, this led to tumor shrinkage of > 50% after 4 months of therapy, which permitted surgical resection. Both tumor specimens also showed strong pathologic tumor response. The robust responses observed with cabozantinib, even at reduced doses, suggest it to be an effective neoadjuvant option in RCC. Our novel experience with neoadjuvant cabozantinib, combined with our review of the use of cabozantinib in RCC, indicates that providing preoperative cabozantinib to facilitate potentially curative surgical resection has good results and should be further explored.     

Impact of Systemic Therapy in Metastatic Renal-Cell Carcinoma Patients With Synchronous and Metachronous Brain Metastases

BackgroundModern radiation techniques have led to significant improvements in intracranial disease control and overall survival (OS) for metastatic renal-cell carcinoma (mRCC) patients diagnosed with brain metastases (BM). The impact of systemic therapy in patients developing mRCC BM remains undercharacterized.Patients and MethodsWe performed a retrospective cohort study of mRCC patients diagnosed with BM. Patients were grouped as having either metachronous BM (ie, ≥ 3 months from mRCC diagnosis) or synchronous BM (ie, < 3 months from mRCC diagnosis). Details of patient demographics, BM, systemic therapy, and outcomes were extracted. Statistical analysis comprised chi-square tests, analysis of variance, and Kaplan-Meier method to characterize survival outcomes.ResultsSeventy-four patients were identified (40 at ≥ 3 months from mRCC diagnosis and 34 at < 3 months from mRCC diagnosis) of which 72 (97%) received local therapy for their BM. Median (interquartile range [IQR]) duration while first line treatment was longer at 7.8 (3.6-17.0) versus 5.1 (3.3-12.6) in patients with metachronous BM versus patients with synchronous BM (P = 0.6), respectively. After BM diagnosis, the metachronous BM cohort continued to receive the same systemic therapy for a median (IQR) duration of 1.9 (0.4-5.5) months, with eventual change most commonly the result of extracranial disease progression. Median (IQR) OS from mRCC diagnosis favored metachronous BM patients versus synchronous BM patients, at 64.2 (31.4-not yet reached) versus 22.4 (9.7-34.1) months (P = .003), respectively. However, this was not significantly different from the time of BM diagnosis, with median (IQR) survival of 20.6 (9.2-31.2) versus 15.7 (11.6-not yet reached) months (P = .95), respectively.ConclusionProlonged OS was found for mRCC patients with BM that presented either metachronously or synchronously. For patients diagnosed with metachronous BM, the development of BM may be an early sign of systemic therapy failure.     

Safety and Efficacy of Pazopanib in First-Line Metastatic Renal-Cell Carcinoma With or Without Renal Failure: CORE-URO-01 Study

Background

Pazopanib has been approved for first-line treatment of patients with metastatic renal-cell carcinoma on the basis of clinical trials that enrolled only patients with adequate renal function. Few data are available on the safety and efficacy of pazopanib in patients with renal insufficiency. This study investigated the effect of kidney function on treatment outcomes in such patients.

Tolerance of Sunitinib in Dialyzed Patients With Metastatic Renal Cell Carcinoma

The use of sunitinib in dialysis patients is poorly described but is of clinical importance. We report 2 cases of patients receiving sunitinib for metastatic renal cell carcinoma while undergoing dialysis. The first patient is undergoing hemodialysis and, though responding to sunitinib, is having significant fatigue and hypertension. The second patient underwent peritoneal dialysis and also had significant problems with hypertension. The tolerance of sunitinib in the setting of dialysis can be challenging as these interventions can have synergistic side effects. Close monitoring for toxicity and dosage manipulations might be required if such therapy is attempted.     

Carcinoma of Unknown Primary Site (CUP) With Metastatic Renal-Cell Carcinoma (mRCC) Histologic and Immunohistochemical Characteristics (CUP-mRCC): Results From Consecutive Patients Treated With Targeted Therapy and Review of Literature

Background

Carcinoma of unknown primary site (CUP) is a heterogenous group of metastatic cancer with no detectable primary tumor site. Diagnostic assessment occasionally presents CUP with metastatic renal-cell carcinoma (mRCC) histologic and immunohistochemical characteristics (CUP-mRCC). Efficacy and toxicity data for vascular endothelial growth factor inhibitor therapies in CUP-mRCC patients are few.

Clinical Outcomes of First-line Sunitinib Followed by Immuno-oncology Checkpoint Inhibitors in Patients With Metastatic Renal Cell Carcinoma

BackgroundThe present retrospective, longitudinal cohort study assessed the association between the first-line sunitinib treatment duration and clinical outcomes with second-line immuno-oncology (IO) therapy among patients with metastatic renal cell carcinoma (mRCC).Patients and MethodsA total of 161 patients with mRCC who had been treated with first-line sunitinib and subsequent IO therapy from select International mRCC Database Consortium centers were included. The overall survival, time to next therapy, time to treatment discontinuation, and real-world physician-assessed best response measured from IO therapy initiation were analyzed and compared between patients treated with first-line sunitinib for ≥ 6 months and those treated for < 6 months.ResultsThe 116 patients treated with sunitinib for ≥ 6 months tended to be older and to have a better International mRCC Database Consortium risk than the 45 patients treated for < 6 months (favorable, 36% vs. 8%, P = .001; intermediate, 59% vs. 70%, P = .21; poor, 5% vs. 22%, P = .007). The receipt of sunitinib for ≥ 6 months versus < 6 months was associated with longer survival (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.21-0.87; P = .02). No significant association was observed between the first-line sunitinib duration and second-line IO outcomes, including the time to next therapy (HR, 0.89; 95% CI, 0.52-1.51; P = .66), time to treatment discontinuation (HR, 0.85; 95% CI, 0.54-1.34; P = .49), and tumor response (odds ratio, 0.73; 95% CI, 0.22-2.49; P = .62).ConclusionsWe found no statistically significant association between the first-line sunitinib duration and clinical outcomes with second-line IO therapy. Patients receiving first-line sunitinib for ≥ 6 months compared with < 6 months was associated with better overall survival, although potential unadjusted confounders could have been present. These findings support the paradigm that previous therapy will not dictate the effectiveness of subsequent immunotherapy.     

Sunitinib Rechallenge in Patients With Metastatic Renal Cell Carcinoma

BackgroundSunitinib has been the standard of care for patients with metastatic renal cell carcinoma (mRCC). However, nearly all patients will eventually develop resistance. Before the introduction of novel agents, few treatment options remained after sunitinib failure. Sunitinib rechallenge is a strategy based on the presumption that resistance might be only temporary. The aim of this analysis was to evaluate the efficacy and safety of sunitinib rechallenge in patients with mRCC.Patients and MethodsPatients who had undergone sunitinib rechallenge (SU2) at the Medical University of Vienna from 2010 to 2017 were identified for the present retrospective study. The primary endpoint was the treatment duration with rechallenge (TD^SU2). The secondary endpoints included the treatment duration with upfront sunitinib (TD^SU1), progression-free survival (PFS^SU1 and PFS^SU2), overall survival (OS^SU1 and OS^SU2), the objective response rate in both settings (ORR^SU1 and ORR^SU2), and toxicity.ResultsA total of 31 patients were eligible. The median TD^SU2 was 7.2 months, and the median TD^SU1 was 17.8 months. The median OS^SU1 and OS^SU2 was 57.9 months and 14.7 months, respectively. The median PFS^SU1 and PFS^SU2 was 14.2 months and 5.6 months, respectively. The ORR^SU1 and ORR^SU2 was 34% and 16%, and another 48% and 42% achieved stable disease (SD), respectively. Fatigue and hypertension were the most common adverse events.ConclusionsSunitinib rechallenge appears to benefit patients in later treatment lines. With the abundance of novel treatment options available, this approach might appear less relevant. However, novel agents are not yet available everywhere. Thus, sunitinib rechallenge could be an additional strategy to improve the outcomes of patients with mRCC.     

Association Between Pretreatment Neutrophil-to-Lymphocyte Ratio and Outcome of Patients With Metastatic Renal-Cell Carcinoma Treated With Nivolumab

Background

Biomarkers to guide treatment in metastatic renal-cell carcinoma (mRCC) are lacking. We aimed to investigate the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and outcome of patients with mRCC receiving nivolumab.

Real-world Experience With Sunitinib Treatment in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to Risk Score

BackgroundADONIS 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.Patients and MethodsPatients 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.ResultsFor all patients in this analysis (N = 467), the median progression-free survival was 23.8 months (95% confidence interval [CI], 16.5-28.5 months), 11.8 months (95% CI, 8.1-17.4 months), and 4.6 months (95% CI, 2.5-7.7 months) for IMDC favorable-, intermediate-, and poor-risk groups, respectively. The median overall survival was 97.1 months (95% CI, 46.3 months-not evaluable [NE]), 33.5 months (95% CI, 20.5-46.6 months), and 10.0 months (95% CI, 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), the median overall survival for IMDC favorable-, intermediate-1, and intermediate-2 risk factors was 21.6 months (95% CI, 16.3 months-NE), 20.5 months (15.5 months-NE), and 15.1 months (4.1 months-NE), respectively.ConclusionsFor patients overall and by risk-group stratification, survival estimates were aligned with previously published data. In patients with intermediate-1 risk, overall survival was very similar to patients with favorable risk. However, further exploration of outcome data from different sources is needed to confirm these observations.     

Multicenter Phase 2 Trial of Gemcitabine,Carboplatin, and Sorafenib in Patients With Metastatic or Unresectable Transitional-Cell Carcinoma

Background

Sorafenib, an oral tyrosine kinase inhibitor, may enhance the antitumor activity of platinum-based chemotherapy in transitional-cell carcinoma. This study investigated the safety and clinical outcome of adding sorafenib to gemcitabine and carboplatin for patients with advanced transitional-cell carcinoma.

Clinical Outcomes of Patients With Chronic Myeloid Leukemia With Concurrent Core Binding Factor Rearrangement and Philadelphia Chromosome

BackgroundAcquisition of additional cytogenetic abnormalities (ACAs) in addition to Philadelphia chromosome is frequently observed in patients with chronic myeloid leukemia (CML) in advanced phase. The presence of core binding factor (CBF) translocations determines the diagnosis of acute myeloid leukemia regardless of blast percentage, and CBF rearrangements are rarely identified as ACAs.Patients and MethodsA retrospective chart review of patients with CML who had CBF rearrangement, t(8;21) or inv(16), in Philadelphia chromosome-positive clones was conducted. Additional cases of CML with CBF rearrangements were identified through literature review.ResultsBetween August 1997 and December 2014, we identified 11 patients who had Philadelphia chromosome and CBF rearrangement in the same clones: 1 (9%) with t(8;21) and 10 (91%) with inv(16). Nine (82%) patients were in blast phase, and 2 (18%) in second chronic phase. Four (36%) patients received tyrosine kinase inhibitor monotherapy, 2 (18%) received tyrosine kinase inhibitor and chemotherapy, and 5 (45%) received chemotherapy only. Three (27%) patients achieved complete remission with incomplete count recovery, and 4 (36%) had no response after the initial therapy. Three (27%) patients underwent allogeneic stem cell transplantation. The median event-free survival and overall survival for the 11 patients were 2 months and 6 months, respectively. Literature review identified 14 patients with CML with CBF rearrangement with a median overall survival of 14 months.ConclusionAcquisition of CBF rearrangement in addition to Philadelphia chromosome is a rare phenomenon associated with poor prognosis. CBF rearrangements as ACAs in patients with CML can be considered high-risk features.