Modest efficacy of nivolumab plus ipilimumab in patients with papillary renal cell carcinoma

2020 ◽  
Author(s):  
Hidekazu Tachibana ◽  
Tsunenori Kondo ◽  
Hiroki Ishihara ◽  
Hironori Fukuda ◽  
Kazuhiko Yoshida ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Response Rate ◽  
Clear Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Papillary Renal Cell Carcinoma ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

Abstract Purpose Combined immunotherapy of nivolumab plus ipilimumab for intermediate- and poor-risk metastatic clear cell renal cell carcinoma showed prolonged progression-free survival and high objective response rate in a randomized phase III clinical trial. However, the efficacy of this treatment for papillary renal cell carcinoma remains unclear. In the present study, we analysed the efficacy of nivolumab plus ipilimumab therapy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Materials and Methods This is a retrospective study of 30 patients with metastatic renal cell carcinoma who received nivolumab and ipilimumab as first-line therapy between December 2015 and May 2020. The objective response rate, progression-free survival and toxicity were compared between the two groups (clear cell renal cell carcinoma and papillary renal cell carcinoma). Results Out of 30 patients, 7 and 23 were diagnosed with papillary renal cell carcinoma and clear cell renal cell carcinoma, respectively. With a median follow-up of 7.2 months, the median progression-free survival was significantly shorter in papillary renal cell carcinoma than in clear cell renal cell carcinoma (2.4 vs. 28.1 months, P = 0.014). Of the seven patients with papillary renal cell carcinoma, one had partial response, one had stable disease and five had progressive disease, resulting in an objective response rate of 14.2%, which was lower compared to that of clear cell renal cell carcinoma (14.2 vs. 52.1%, P = 0.06). Discontinuation due to toxicity was not observed with papillary renal cell carcinoma, meanwhile 60.8% of patient with clear cell renal cell carcinoma discontinued treatment due to toxicity. Conclusion Nivolumab plus ipilimumab had modest efficacy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Nivolumab plus ipilimumab remains an option for a limited number of patients with intermediate- or poor-risk papillary renal cell carcinoma.

scholarly journals NOVEL PLASMA GLYCOPROTEIN BIOMARKERS PREDICT PROGRESSION-FREE SURVIVAL IN SURGICALLY RESECTED CLEAR CELL RENAL CELL CARCINOMA

2022 ◽  
Author(s):  
Daniel Serie ◽  
Amanda A Myers ◽  
Daniela A Haehn ◽  
Alexander Parker ◽  
Essa Bajalia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differential Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Progression Free Survival ◽  
P Value ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Kaplan Meier

Introduction: Limited data exists on utilization of protein post-translational modifications as biomarkers for clear cell renal cell carcinoma (ccRCC). We employed high-throughput glycoproteomics to evaluate differential expression of glycoprotein-isoforms as novel markers for ccRCC progression-free survival (PFS). Methods: Plasma samples were obtained from 77 patients treated surgically for ccRCC. Glycoproteomic analyses were carried out after liquid chromatography tandem mass spectrometry. Age-adjusted Cox proportional hazard models were constructed to evaluate PFS. Optimized Harrells c-index was employed to dichotomize the collective for the construction of Kaplan-Meier curves. Results: The average length of follow-up was 3.4 (range: 0.04-9.83) years. Glycoproteomic analysis identified 39 glycopeptides and 14 non-glycosylated peptides that showed statistically significant (false discovery rate p ≤0.05) differential expression associated with PFS. Five of the glycosylated peptides conferred continuous hazard ratio of > 6 (range 6.3-11.6). These included prothrombin A2G2S glycan motif (HR=6.47, P=9.53E-05), immunoglobulin J chain FA2G2S2 motif (HR=10.69, P=0.001), clusterin A2G2 motif (HR=7.38, P=0.002), complement component C8A A2G2S2 motif (HR=11.59, P=0.002), and apolipoprotein M glycopeptide with non-fucosylated and non-sialylated hybrid-type glycan (HR=6.30, P=0.003). Kaplan-Meier curves based on dichotomous expression of these five glycopeptides resulted in hazard ratios of 3.9-10.7, all with p-value < 0.03. Kaplan-Meyer plot using the multivariable model comprising 3 of the markers yielded HR of 11.96 (p <0.0001). Conclusion: Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.

scholarly journals Predictors of Progression-Free Survival and Overall Survival in Metastatic Non-Clear Cell Renal Cell Carcinoma: A Single-Center Experience

2019 ◽  
Vol 10 (2) ◽  
pp. 101-111 ◽  
Author(s):  
Sasanka Kumar Barua ◽  
Yashasvi Singh ◽  
Saumar Jyoti Baruah ◽  
Rajeev T.P. ◽  
Puskal K. Bagchi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Single Center ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Single Center Experience

scholarly journals Predicting Clear Cell Renal Cell Carcinoma Survival Using Kurtosis of Cytoplasm in the Hematoxylin Channel from Histology Slides

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Jun Wang ◽  
Jianhui Chen ◽  
Liren Jiang ◽  
Qi Wu ◽  
Dawei Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Survival Analysis ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Renal Cell ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

Purpose. Grade-dependent decrease of lipid storage in clear cell renal cell carcinoma (ccRCC) leads to morphology changes in HE sections. This study investigated the role of cytoplasmic features in frozen sections of ccRCC on prognosis using the digital pathology approach. Methods. We established an automatic pipeline that performed tumor region selection, stain vector normalization, nuclei segmentation, and feature extraction based on the pathologic data from Shanghai General Hospital and The Cancer Genome Atlas database. Extracted features were subjected to survival analysis. Results. Kurtosis of the cytoplasm in the hematoxylin channel was correlated with progression-free survival (HR 0.10, 95% CI: 0.04–0.24, p = 6.52 ∗ 10 − 7 ) and overall survival (HR 0.11, 95% CI: 0.05–0.31, p = 1.72 ∗ 10 − 5 ) in ccRCC, which outperformed other texture features in this analysis. Multivariate Cox regression analysis revealed that low kurtosis of cytoplasm in the hematoxylin channel was an independent predictor for a shorter progression-free survival time ( p = 0.044 ) and overall survival time (p = 0.01). Kaplan–Meier survival analysis of progression-free survival and overall survival also showed a significantly worse prognosis in patients with low kurtosis of the cytoplasm in the hematoxylin channel (both p < 0.0001 ). Lower kurtosis of cytoplasm in the hematoxylin channel was associated with higher pathologic grade, less cholesterol ester, and more mitochondrial DNA content. Conclusion. Kurtosis of the cytoplasm in the hematoxylin channel predicts survival in clear cell renal cell carcinoma.

Prognostic and predictive role of intra-tumoral CXCR1 expression in patients receiving tyrosine kinase inhibitors for metastatic clear-cell renal cell carcinoma

2021 ◽  
pp. 205141582110122
Author(s):  
Sridhar Panaiyadiyan ◽  
Brusabhanu Nayak ◽  
Prabhjot Singh ◽  
Seema Kaushal ◽  
Subhradip Karmakar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

Objective: We aimed to evaluate the role of intra-tumoral CXCR1 expression in predicting prognosis and treatment response in metastatic clear-cell renal cell carcinoma patients receiving tyrosine kinase inhibitors. Materials and methods: Patients with metastatic clear-cell renal cell carcinoma presented between February 2018–December 2019 were studied for the CXCR1 expression in tumor tissues before starting tyrosine kinase inhibitors. Primary outcome measure was progression-free survival. Secondary outcome measures included overall survival and prediction of treatment response. Results: The study included 35 patients with a mean age of 53.6±9.6 years. At a mean follow-up of 12.2±4.1 months, 17 (48.6%) patients had disease progression including eight (22.9%) deaths. Patients with high CXCR1 expression, compared to those with low CXCR1 expression, had a significantly shorter 12-month progression-free survival (35.4% vs 77.9%, p=0.01) and an insignificant impact on 12-month overall survival. The CXCR1 expression scores significantly differed between patients with progressive and nonprogressive disease (20.1 vs 15.1, p=0.01) and patients with high CXCR1 expression had a reduced benefit from tyrosine kinase inhibitors. The multivariate Cox regression analysis showed CXCR1 expression as a significant predictor of progression-free survival. Conclusion: High intra-tumoral CXCR1 expression before tyrosine kinase inhibitors can be an independent prognostic factor for progression-free survival and predictor of reduced benefit in patients with metastatic clear-cell renal cell carcinoma. Level of evidence: Level 2b.

Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study

2015 ◽  
Vol 33 (30) ◽  
pp. 3431-3438 ◽  
Author(s):  
Michael B. Atkins ◽  
Gwenaelle Gravis ◽  
Kazimierz Drosik ◽  
Tomasz Demkow ◽  
Piotr Tomczak ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Renal Cell ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival

Purpose Trebananib, an investigational recombinant peptide-Fc fusion protein, neutralizes the receptor-ligand interaction between Tie2 and angiopoietin-1/2. This phase II study was conducted to evaluate trebananib plus sunitinib, a vascular endothelial growth factor receptor inhibitor, in patients with metastatic clear cell renal cell carcinoma. Patients and Methods Adults with metastatic renal cell carcinoma were enrolled sequentially onto two cohorts that received sunitinib 50 mg once per day for 4 weeks on and 2 weeks off and intravenous trebananib once per week at a dose of 10 mg/kg in cohort A or 15 mg/kg in cohort B. The primary end points were incidences of adverse events (AEs) and dose interruptions of sunitinib during the first 12 weeks of treatment. Secondary end points included objective response rate and progression-free survival. Results Eighty-five patients were enrolled: 43 in cohort A, and 42 in cohort B. During the first 12 weeks of treatment, 58% and 57% of patients in cohorts A and B, respectively, had sunitinib dose interruptions (dose decrease, withholding, or withdrawal). The most frequent AEs were diarrhea (cohort A, 74%; cohort B, 67%), mucosal inflammation (cohort A, 49%; cohort B, 60%), and hypertension (cohort A, 52%; cohort B, 45%). AEs of grade 3 or greater occurred in 58% of patients in cohort A and in 69% of patients in cohort B. The objective response rate was 58% and 63% in cohorts A and B, respectively. The median progression-free survival time was 13.9 months (95% CI, 10.4 to 19.2) and 16.3 months (95% CI, 13.1 to 21.4) in cohorts A and B, respectively. The median overall survival time was 36 months (95% CI, 25.2 to not estimable) in cohort A and was not estimable (median follow-up, 25 months) in cohort B. Conclusion Trebananib plus sunitinib seemed to increase toxicity at the tested doses. Efficacy results suggest a potential benefit for the addition of trebananib to sunitinib.

199 PHD3 expression is a predictor of progression-free survival in clear cell renal cell carcinoma

2012 ◽  
Vol 11 (1) ◽  
pp. e199-e199a
Author(s):  
T. Tanaka ◽  
H. Kitamura ◽  
T. Torigoe ◽  
Y. Hirohashi ◽  
N. Masumori ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

scholarly journals Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study

2021 ◽  
pp. JCO.21.00939
Author(s):  
Sumanta K. Pal ◽  
Bradley McGregor ◽  
Cristina Suárez ◽  
Che-Kai Tsao ◽  
William Kelly ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
End Point

PURPOSE COSMIC-021 is evaluating cabozantinib plus atezolizumab in patients with solid tumors. We report results from patients with advanced clear cell (cc) and non–clear cell (ncc) renal cell carcinoma (RCC). METHODS This phase Ib study ( NCT03170960 ) enrolled patients age ≥ 18 years with advanced RCC. A dose-escalation stage was followed by expansion cohorts. For cohort expansion, prior systemic therapy was not permitted for ccRCC but allowed for nccRCC. Patients received oral cabozantinib 40 mg once a day (ccRCC and nccRCC) or 60 mg once a day (ccRCC only) plus atezolizumab (1,200 mg intravenously, once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1; the secondary end point was safety. RESULTS A total of 102 patients were enrolled. Median follow-up was 25.8, 15.3, and 13.3 months for the 40-mg ccRCC, 60-mg ccRCC, and nccRCC groups, respectively. ORR was 53% (80% CI, 41 to 65) in the 40-mg ccRCC group (n = 34) and 58% (80% CI, 46 to 70) in the 60-mg ccRCC group (n = 36), 3% and 11%, respectively, with complete response; median progression-free survival (exploratory end point) was 19.5 and 15.1 months, respectively. In nccRCC (n = 32), ORR was 31% (80% CI, 20 to 44), all partial responses; median progression-free survival was 9.5 months. Grade 3 or 4 treatment-related adverse events (TRAEs) were reported by 71% of patients in the 40-mg ccRCC group, 67% in the 60-mg ccRCC group, and 38% in the nccRCC group; TRAEs leading to discontinuation of both agents occurred in 15%, 6%, and 3% of patients, respectively. There were no grade 5 TRAEs. CONCLUSION The novel combination of cabozantinib plus atezolizumab demonstrated encouraging clinical activity and acceptable tolerability in patients with advanced ccRCC and nccRCC. Disease control was observed across dose levels and histologic subtypes.

scholarly journals Safety and Efficacy of Nivolumab in Brain Metastases From Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study

2019 ◽  
Vol 37 (23) ◽  
pp. 2008-2016 ◽  
Author(s):  
Ronan Flippot ◽  
Cécile Dalban ◽  
Brigitte Laguerre ◽  
Delphine Borchiellini ◽  
Gwénaelle Gravis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma

PURPOSE Nivolumab is standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies, but its activity on brain metastases from ccRCC remains unknown, because these patients were excluded from pivotal studies. We aimed to assess the activity of nivolumab in this population. METHODS The GETUG-AFU 26 NIVOREN phase II trial assessed the activity and safety of nivolumab in patients with metastatic ccRCC who failed vascular endothelial growth factor–directed therapies ( ClinicalTrials.gov identifier: NCT03013335 ). Patients with asymptomatic brain metastases were prospectively identified and underwent dedicated brain evaluation. Two cohorts were constituted: cohort A comprised patients with previously untreated brain metastases, and cohort B comprised patients whose brain metastases underwent prior therapy. The primary end point was intracranial response rate in cohort A. RESULTS Seventy-three patients with brain metastases were included: 39 in cohort A and 34 in cohort B. Intracranial response rate was 12% in cohort A; no objective response was reported in patients with brain lesions that were multiple or larger than 1 cm. Median intracranial progression-free survival was 2.7 months (95% CI, 2.3 to 4.6 months) in cohort A and 4.8 months (95% CI, 3.0 to 8.0 months) in cohort B, with adjusted hazard ratio of 2.04 (95% CI, 1.08 to 3.83). Overall survival rate at 12 months was 67% (95% CI, 49.6% to 79.1%) in cohort A and 59% (95% CI, 40.6% to 73.2%) in cohort B. Most patients in cohort A (72%) needed subsequent focal brain therapy. Nivolumab was well tolerated, with no unexpected toxicity. CONCLUSION Nivolumab activity is limited in patients with untreated brain metastases from ccRCC. Brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC.

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