Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies

Lee

et al. 2017

CUAJ

Introduction: The aim of this study was to investigate the real-world clinical outcomes of first-line pazopanib and second-line everolimus in Korean patients with metastatic renal cell carcinoma (mRCC). Methods: Data of patients who had mRCC with clear-cell component between 2001 and 2015 at multiple institutions were collected retrospectively. To be included in the analysis, patients had to meet the following criteria: age≥18 years; received first-line targeted therapy with pazopanib; and received second-line targeted therapy with everolimus. The primary outcomes included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Results: A total of 36 patients were included in the analysis. The median followup period was 33.5 months (range 17-49.5). The median PFS was eight months (95% confidence interval [CI] 6.4-9.6) after treatment with pazopanib and three months (95% CI 1.9-4.1) with everolimus. The median OS was 27 months (95% CI 16.6-37.4). The median treatment duration was seven months (range 4.3-10.8) after treatment with pazopanib and 3.5 months (range 3-4) with everolimus. Multivariate analysis revealed that the Heng risk criteria were independently associated with OS (p<0.001). Almost every patient experienced some form of AE, the majority of which were mostly mild or moderate in severity. The most common AEs were diarrhea (50%), hypertension (44.4%), and fatigue (41.7%) after treatment with pazopanib, and anemia (47.2%), stomatitis (41.7%), and fatigue (38.9%) with everolimus. Conclusions: The outcomes for the patients treated with pazopanib followed by everolimus in Korea as observed by us were consistent with those reported by previous studies. The Heng risk criteria were significantly associated with the prognosis of patients with mRCC. AEs were mainly mild to moderate and readily managed.

Section: Cuaj -Original Researchmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical outcomes of the sequential use of pazopanib followed by everolimus for the treatment of metastatic renal cell carcinoma: A multicentre study in Korea

Lee

et al. 2017

CUAJ

“…With few exceptions, such as myeloma and lymphoma, systemic therapy has little impact in this regard. It is unknown whether the newer biologics, such as sorafenib for renal cell carcinoma, have the same responses in bone metastases as visceral disease even if the driver mutation is present 21 . Our experience with the use of biologics in treating SM is somewhat mixed and inconsistent, and on this basis, is not considered in the setting of high-grade spinal cord compression or symptomatic lesions.…”

Section: Patient's Evaluation -Treatment Decision Processmentioning

confidence: 99%

An update in the management of spinal metastases

Joaquim

Powers

Laufer

et al. 2015

Arq. Neuro-Psiquiatr.

Advances in cancer treatment over the past decade, such biologics and immunotherapy are improving patient outcomes and consequently life expectancy. The most common sites for metastases in the general population with cancer are the liver and lungs, followed by bone. Considering bone metastases, the majority will affect the spine 1 . Some studies estimate that up to 40% of all patients with cancer will have spinal metastases (SM) during the course of their disease 2,3 . The most frequent histologic types of cancer that give rise to bone metastases are breast, prostate and lung cancer 4 . Most of the spinal metastases are diagnosed following the diagnosis of the primary cancer. However, in about 10% of the patients, SM is the first manifestation of an unknown primary tumor 1 . Spinal cord compression is expected in up to 20% of the patients with SM. Approximately 95% of the patients with SM will demonstrate epidural metastases, mainly affecting the vertebral body and the pedicle regions, whereas 5% will present with intradural and less than 1% with intramedullary metastases 5,6 . Symptomatic spinal cord compression occurs more frequently in the thoracic spine, followed by cervical and then lumbar. The greater incidence of SM in the thoracic spine is attributed to the higher number of vertebrae and small canal diameter AbstrActThe best clinical treatment for spinal metastases requires an integrated approach with input from an interdisciplinary cancer team. The principle goals of treatment are maintenance or improvement in neurologic function and ambulation, spinal stability, durable tumor control, and pain relief. The past decade has witnessed an explosion of new technologies that have impacted our ability to reach these goals, such as separation surgery and minimally invasive spinal procedures. The biggest advance, however, has been the evolution of stereotactic radiosurgery that has demonstrated durable tumor control both when delivered as definitive therapy and as a postoperative adjuvant even for tumors considered markedly resistant to conventional external beam radiation. In this paper, we perform an update on the management of spinal metastases demonstrating the integration of these new technologies into a decision framework NOMS that assesses four basic aspects of a patient's spine disease: Neurologic, Oncologic, Mechanical Instability and Systemic disease.Keywords: spinal metastases, bone metastases, diagnosis, management, treatment, NOMS.resumo O tratamento dos pacientes com metástases na coluna requer uma abordagem multidisciplinar por equipe especializada em oncologia. Os objetivos básicos do tratamento são a manutenção/ melhora da função neurológica com preservação da deambulação, manutenção da estabilidade da coluna, controle tumoral e alívio da dor. A última década testemunhou uma explosão de novas tecnologias que auxiliaram a atingir os objetivos terapêuticos, como a cirurgia de separação e procedimentos minimamente cirúrgicos minimamente invasivos. Contudo, o maior avanço terapêutico constitui-se d...

“…7,9,10 However, within a year of starting a first targeted therapy, most patients develop resistance to treatment and receive a second and, often, a third targeted therapy. 5,8,[11][12][13][14][15] Thus, deciding which targeted therapies should be used after failure of the first one -and in which sequence -amid a growing number of treatment options is a challenge.…”

mentioning

confidence: 99%

“…9,18 Given the lack of consensus on the optimal treatment sequences for aRCC, available targeted therapies are likely to be used differently across clinical practices. For this reason, several studies have been carried out to assess real-world treatment patterns.…”

mentioning

confidence: 99%

Patterns of care among patients receiving sequential targeted therapies for advanced renal cell carcinoma: A retrospective chart review in the USA

Pal

Signorovitch

et al. 2017

Int J of Urology

Self Cite

Objectives: To assess real-world treatment patterns of targeted therapies after failure of first-line tyrosine kinase inhibitors in patients with advanced renal cell carcinoma. Methods: A large, retrospective review of medical charts of patients with advanced renal cell carcinoma in the USA was carried out. Descriptive statistics were used to summarize physicians' and patients' characteristics, treatment sequences, and reasons for treatment choices. P-values were calculated using v 2 -tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. A descriptive comparison was carried out between current results and those of a previous treatment pattern study conducted in 2012 to identify changes in treatment patterns over time. Results: Sunitinib and everolimus remained the most commonly-used first and second targeted therapies, respectively. Among patients who continued to a third targeted therapy, everolimus and axitinib were the most commonly-used treatments after second targeted therapy with a tyrosine kinase inhibitor and a mammalian target of rapamycin inhibitor, respectively. The use of pazopanib as first targeted therapy, and of axitinib and sorafenib as second targeted therapies, increased over time. Efficacy, treatment guidelines and a different mechanism of action were the main reasons given by physicians for choosing among second targeted therapies after failure of a first tyrosine kinase inhibitor. Conclusions:The results of the present study document patterns of care during a period of rapid and ongoing therapeutic advancement in advanced renal cell carcinoma. Sequencing of therapies warrants ongoing analysis in light of new agents entering the advanced renal cell carcinoma treatment landscape.