Reply to Nirmish Singla and Vitaly Margulis’s Letter to the Editor re: Geraldine Pignot, Antoine Thiery-Vuillemin, Jochen Walz, et al. Nephrectomy After Complete Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma: A New Surgical Challenge? Eur Urol. In press. https://doi.org/10.1016/j.eururo.2019.12.018. The Next Surgical Frontier in Kidney Cancer: Nephrectomy After Immune Checkpoint Inhibition

2020 ◽  
Vol 78 (2) ◽  
pp. e81-e82
Author(s):  
Géraldine Pignot ◽  
Antoine Thiery-Vuillemin ◽  
Jochen Walz ◽  
Pierre Bigot ◽  
Karim Bensalah ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition

Nephrectomy after complete response to immune checkpoint inhibitors for metastatic renal cell carcinoma (mRCC): A new surgical challenge?

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 707-707
Author(s):  
Geraldine Pignot ◽  
Antoine Thiery-Vuillemin ◽  
Jochen Walz ◽  
Herve Lang ◽  
Pierre Werle ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Metastatic Sites

707 Background: In the current era of Immune checkpoint inhibitors (ICI), the role and timing of nephrectomy in the case of complete response on metastatic sites is still unknown. We aimed to evaluate the feasibility of nephrectomy for residual disease in patients with metastatic renal cell carcinoma (mRCC) and complete response (CR) on metastatic sites following ICI. Methods: Patients who underwent partial or radical nephrectomy after prior ICI between 2015 and 2018 were retrospectively included and clinicopathological data were reviewed. Perioperative data and postoperative outcomes were recorded. Results: Eleven patients without initial cytoreductive nephrectomy at diagnosis underwent delayed nephrectomy after long ICI administration because of complete response on metastatic sites. Median age was 59.8 years [38-67]. All patients had clear cell RCC on the initial biopsy. IMDC prognostic group was intermediate (81.8%) or poor (18.2%). ICI was administered as first-line therapy in 36.4% of cases (4/11) and as second-line option after TKI in 63.6% of cases (7/11). Treatments regimens were: nivolumab + ipilimumab (n = 3), nivolumab + tivozanib (n = 2) or nivolumab alone (n = 6). The median duration of ICI treatment was 10 months (range: 3-38 months) and the mean number of cycles was 27 (range: 6-75). Median operative time was 243 minutes [135-345] and mean blood loss was 909 cc [40-4000]. In 81.8% (n = 9) of the cases, surgeons experienced challenges for finding dissection planes due to inflammatory infiltration. The 30-day Clavien-Dindo postoperative complication rate was 54.6%, including 1 surgery-related death. Pathological report showed lymphocyte and/or macrophage infiltration in 54.6% and complete pathological response in 2 cases. Median follow-up was 15 months, with 73% of patients free from progression and 54% free from systemic treatment at 1 year. Conclusions: Nephrectomy following ICI for mRCC could allow achieving CR in selected patients. Due to technically complexity and complications rates, this surgery should be performed in centers with extensive experience.

scholarly journals Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Revati Sharma ◽  
Elif Kadife ◽  
Mark Myers ◽  
George Kannourakis ◽  
Prashanth Prithviraj ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Resistance Mechanisms ◽  
Number Of Patients ◽  
Angiogenesis Pathway

AbstractVascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported. One of the mechanisms of VEGF-TKIs is inhibition of the classical angiogenesis pathway. However, recent studies have shown the restoration of an alternative angiogenesis pathway in modulating resistance. Further, in the last 5 years, immune checkpoint inhibitors (ICIs) have revolutionized RCC treatment. Although some patients exhibit potent responses, a non-negligible number of patients are innately resistant or develop resistance within a few months to ICI therapy. Hence, an understanding of the mechanisms of VEGF-TKI and ICI resistance will help in formulating useful knowledge about developing effective treatment strategies for patients with advanced RCC. In this article, we review recent findings on the emerging understanding of RCC pathology, VEGF-TKI and ICI resistance mechanisms, and potential avenues to overcome these resistance mechanisms through rationally designed combination therapies.

Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4583-4583
Author(s):  
Chris Labaki ◽  
Sarah Abou Alaiwi ◽  
Andrew Lachlan Schmidt ◽  
Talal El Zarif ◽  
Ziad Bakouny ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
High Dose ◽  
Line Of Therapy

4583 Background: The use of High-Dose Corticosteroids (HDC) has been linked to poor outcomes in patients with lung cancer treated with immune checkpoint inhibitors (ICIs) (Ricciuti B, JCO, 2019). There is no data on the effect of HDC on renal cell carcinoma patients (RCC) treated with immunotherapy. We hypothesized that HDC use would be associated with worse outcomes in RCC patients receiving ICIs. Methods: This study evaluated a retrospective cohort of patients with RCC at Dana-Farber Cancer Institute in Boston, MA. Clinical information including demographics, IMDC risk score, RCC histology, steroid administration, ICI regimen, line of therapy, time to treatment failure (TTF) and overall survival (OS) were collected. Patients were divided into those receiving HDC (prednisone ≥10 mg or equivalent for ≥ 1 week, HDC group) or not receiving HDC (No-HDC group). HDC administration was evaluated in relation to TTF and OS in a univariate analysis (Log-rank test) and a multivariate analysis (Cox regression). Results: 190 patients with RCC receiving ICIs were included, with a median age of 59 years. HDC were administered to 56 patients and 134 patients received no (N= 116) or only low-dose (N=18) steroids. In the HDC group, 40 patients received steroids for immune-related adverse events, 8 for other cancer-related indications, and 8 for non-oncological indications. There was no difference in TTF between the HDC and No-HDC groups (12-mo TTF rate: 34.8 vs. 32.3%, respectively; log-rank p=0.65). Similarly, there was no difference in OS between the HDC and No-HDC groups (36-mo OS rate: 56.7 vs. 62.4%, respectively; log-rank p=0.97). After adjusting for IMDC risk group, RCC histology, ICI regimen type, and line of therapy, TTF and OS did not differ in the HDC group as compared to No-HDC group (HR=1.14 [95%CI: 0.80-1.62], p=0.44 and HR=1.17 [95%CI: 0.65-2.11], p=0.59, respectively). Conclusions: In this retrospective study of patients with RCC treated with ICIs, administration of high-dose corticosteroids was not associated with worse outcomes.[Table: see text]

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