How Targeted Therapy Influence Renal Surgery for Renal Cell Carcinoma

2020 ◽  
Vol 21 (15) ◽  
pp. 1550-1557
Author(s):  
Francesco Greco ◽  
Michele Marchioni ◽  
Francesco Esperto ◽  
Rocco Papalia ◽  
Luigi Schips ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Systemic Treatment ◽  
Target Therapy ◽  
Tumor Resection ◽  
Tumor Diameter

Between the end of 2005 and the beginning of 2006, several new target therapies have been introduced for the treatment of renal cell carcinoma. In this review, we aimed to explore and summarize the main findings of the use of systemic treatment and its effect on surgery in patients with renal cell carcinoma. We identified three different settings: neoadjuvant and adjuvant settings as well as the association of systemic therapy with surgery in the metastatic renal cell carcinoma patients. Neoadjuvant target therapy with tyrosine kinase inhibitor may facilitate the tumor resection and reduce the overall tumor diameter and its complexity. However, most of the evidence is from small phase I or II clinical trials and results are often conflicting without determining a relevant change in the main parameters investigated, such as tumor complexity. In the adjuvant setting, results from pivotal trials investigating the use of tyrosine kinase inhibitors for patients with non-metastatic RCC treated with surgery discourage this practice. Indeed, most of the evidence from single clinical trials and pooled results from meta-analysis failed to find a survival advantage with the use of adjuvant systemic treatment. To date, an improvement of clinical outcomes after systemic targeted therapies could be only found in the setting of cytoreductive nephrectomy. However, the CARMENA and SURTIME trials recently confirmed the evidence against a surgical treatment in patients with mRCC and poor prognosis. In the near future, significant changes may be introduced by the use of immunotherapies.

scholarly journals 18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results

2020 ◽  
Author(s):  
L. M. Mittlmeier ◽  
M. Unterrainer ◽  
S. Rodler ◽  
A. Todica ◽  
N. L. Albert ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Treatment Response ◽  
Renal Cell ◽  
Systemic Treatment ◽  
Response Assessment ◽  
Recist 1.1 ◽  
Psma Pet ◽  
Pet Ct

Abstract Introduction Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. Methods 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8 weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. Results Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. Conclusion On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT.

DNA damage repair (DDR) pathway alteration in advanced renal cell carcinoma (RCC) is association with good progression-free survival with tyrosine kinase inhibitor (TKI) therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 346-346
Author(s):  
Wei Zhai ◽  
Junyun Wang ◽  
Ning He ◽  
Jiale Zhou ◽  
Jianfei Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Damage Repair ◽  
Endothelial Growth Factor

346 Background: Alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may be as potential biomarkers for vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma. However, biologic significance and relevance to TKI targeted therapy in metastatic RCC are unknown. Methods: Genomic data and treatment outcomes were retrospectively collected for patients with metastatic RCC. Tumor and germline DNA were subject to targeted next generation sequencing across 642 genes of interest, including 60 DDR genes. Patients were dichotomized according to underlying DDR gene alteration into (1) DDR gene alterations present (Mut DDR); (2) wildtype (WT) DDR gene alterations present (WT DDR). Association between DDR status and therapeutic benefit was investigated separately for and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy. Results: Mut DDR were detected in 17/40 patients (42.5%). The most frequently DDR altered genes were TP53. For patients with TKI treatment, Mut DDR status was associated with superior progression free survival (log-rank p = 0.048), but not with superior overall survival (log-rank p = 0.39); after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium risks and extent of prior therapy, the HR for Mut DDR was 2.68 (95% CI: 0.96–7.46; p = 0.059). Conclusions: DDR alterations are recurrent genomic events in patients with advanced RCC and were mostly clonal in this cohort. Dysfunction events in these genes may affect outcome with TKI therapy in adanced RCC, and these hypothesis-generating results deserve further study.

Risk of toxicity with immunotherapy–tyrosine kinase inhibitors for metastatic renal cell carcinoma: a meta-analysis of randomized controlled trials

2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Matteo Santoni ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Relative Risks

Aim: Few data are available regarding the safety profile of immunotherapy–tyrosine kinase inhibitor (IO-TKI) combinations in metastatic renal cell carcinoma. The authors investigated all-grade and grade 3–4 (G3–4) adverse events in trials comparing IO-TKI combinations with sunitinib monotherapy. Methods: The relative risks of several all-grade and G3–4 adverse events were analyzed. Results: Relative risks were similar between patients receiving IO-TKI combinations versus sunitinib monotherapy. However, the use of IO-TKI combinations was associated with a higher risk of all-grade and G3–4 diarrhea, all-grade hypothyroidism, G3–4 decreased appetite, all-grade and G3–4 aspartate transaminase increase and all-grade and G3–4 alanine transaminase increase. Conclusion: The results of the authors' meta-analysis suggest that risks of treatment-related adverse events should be carefully considered when choosing IO-TKI combinations in metastatic renal cell carcinoma patients.

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