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.

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 Results of a Multicenter Phase II Study of Atezolizumab and Bevacizumab for Patients With Metastatic Renal Cell Carcinoma With Variant Histology and/or Sarcomatoid Features

2020 ◽  
Vol 38 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Bradley A. McGregor ◽  
Rana R. McKay ◽  
David A. Braun ◽  
Lillian Werner ◽  
Kathryn Gray ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Symptom Index ◽  
Multicenter Phase ◽  
Variant Histology ◽  
Sarcomatoid Differentiation

PURPOSE In this multicenter phase II trial, we evaluated atezolizumab combined with bevacizumab in patients with advanced renal cell carcinoma (RCC) with variant histology or any RCC histology with ≥ 20% sarcomatoid differentiation. PATIENTS AND METHODS Eligible patients may have received previous systemic therapy, excluding prior bevacizumab or checkpoint inhibitors. Patients underwent a baseline biopsy and received atezolizumab 1,200 mg and bevacizumab 15 mg/kg intravenously every 3 weeks. The primary end point was overall response rate (ORR) by RECIST version 1.1. Additional end points were progression-free survival (PFS), toxicity, biomarkers of response as determined by programmed death-ligand 1 (PD-L1) status, and on-therapy quality-of-life (QOL) metrics using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 and the Brief Fatigue Inventory. RESULTS Sixty patients received at least 1 dose of either study agent; the majority (65%) were treatment naïve. The ORR for the overall population was 33% and 50% in patients with clear cell RCC with sarcomatoid differentiation and 26% in patients with variant histology RCC. Median PFS was 8.3 months (95% CI, 5.7 to 10.9 months). PD-L1 status was available for 36 patients; 15 (42%) had ≥ 1% expression on tumor cells. ORR in PD-L1–positive patients was 60% (n = 9) v 19% (n = 4) in PD-L1–negative patients. Eight patients (13%) developed treatment-related grade 3 toxicities. There were no treatment-related grade 4-5 toxicities. QOL was maintained throughout therapy. CONCLUSION In this study, atezolizumab and bevacizumab demonstrated safety and resulted in objective responses in patients with variant histology RCC or RCC with ≥ 20% sarcomatoid differentiation. This regimen warrants additional exploration in patients with rare RCC, particularly those with PD-L1–positive tumors.

Genomic biomarkers of response to nivolumab/ipilimumab (nivo/ipi) and nivolumab (nivo) monotherapy in 108 patients with advanced renal cell carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 641-641 ◽  
Author(s):  
Chung-Han Lee ◽  
Renzo G Di Natale ◽  
Diego Chowell ◽  
Vladimir Makarov ◽  
Almedina Redzematovic ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Multiple Testing ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Genomic Biomarkers ◽  
Predictors Of Response ◽  
Mutation Burden

641 Background: Both the combination of nivo/ipi and nivo monotherapy have shown efficacy across multiple malignancies including clear cell Renal Cell Carcinoma (ccRCC). Biomarkers such as tumor mutation burden (TMB) are prognostic in other malignancies, however, remain unvalidated in ccRCC. This study investigates genomic biomarkers associated with nivo/ipi and nivo clinical response. Methods: Whole exome sequencing (WES) was performed on pretreatment tumor derived DNA from nivo/ipi and nivo treated patients from MSKCC and publicly available WES datasets (Miao D, Science, 2018, 359: 6377). Somatic mutations, TMB, neoantigen load (NA), and HLA zyogosity were correlated to objective response rate (ORR), progression free survival (PFS), and Overall Survival (OS). Alterations occurring in < 10% of the cohort were considered non-evaluable (NE). Results: 108 patients had tumors studied; 32 patients with nivo/ipi and 76 patients with nivo therapy. No individual factors showed significant correlations to ORR or both PFS and OS. In the combined cohort, homozygosity at HLA-C was associated with shorter OS (HR=2.55 95% CI 1.17-5.57; P=0.02). In the nivo/ipi cohort, TMB (HR=0.36 95% CI 0.16-0.84; P=0.02) and NA (HR=0.43 95% CI 0.19-0.98; P=0.04) were associated with longer PFS. Conclusions: Increased TMB and NA load may predict for improved outcomes, and homozygosity at HLA loci may predict for worse outcomes. The predictors of response to nivo may not be generalizable to nivo/ipi. To rule out artifacts of multiple testing in a small cohort, validation in a larger dataset is necessary. [Table: see text]

A phase II open-label study of cabozantinib after first-line treatment including an immune-checkpoint combination in patients with advanced or unresectable renal cell carcinoma: The BREAKPOINT trial (MeetUro trial 03 - EudraCT number 2018-000582-36).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 326-326
Author(s):  
Giuseppe Procopio ◽  
Chiara Pircher ◽  
Melanie Claps ◽  
Valentina Guadalupi ◽  
Alessia Mennitto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
First Line ◽  
Open Label

326 Background: Antiangiogenic therapy has been a milestone in the treatment of metastatic renal cell carcinoma (mRCC) for years. The positive results with immune-checkpoint inhibitors (ICI) are changing the frontline standard of care of mRCC patients (pts). To date, prospective data are lacking to determine the efficacy of antiangiogenic therapy in pts progressed to ICI. The multikinase inhibitor Cabozantinib (cabo) has shown prolonged survival in pre-treated mRCC pts. Moreover, by targeting multiple pathways and crucial kinases involved in microenvironment-driven immune-escape, it may represent an ideal agent to be used sequentially after ICI. Methods: This is the first prospective open label, single arm, multicenter, phase II study to evaluate efficacy and safety of Cabo in pts with mRCC pre-treated with adjuvant or first line PD-1/PD-L1-based therapy (as monotherapy or in combination with an TKI or anti CTLA-4). Cabo 60 mg once daily was administered until progressive disease (PD) or unacceptable toxicity. The primary endpoint was progression free survival (PFS), secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. Results: Among 23 patients enrolled, 22 were included in the analysis (one was excluded for screening failure). Median age was 59.5 years (range: 29-74), 69.5% were male. At baseline, Karnofsky performance status was 100 in 59% of pts, 80-90 in 31.8% and 70-80 in 9%. 22.7% of pts had a good Heng score, 50% intermediate and 27.2% poor. Median duration of the previous therapy with anti PD-1 or anti-PD-L1 compounds was 4.3 months. Pts received an average of 4.7 months of Cabo. Among evaluable cases, 6 pts (27.2%) achieved a partial response and 5 pts (22.7%) stable disease. The median follow-up was 7.2 months and the median PFS was 7.2 months. 2 pts discontinued treatment for toxicity, 8 pts for PD, 1 patient discontinued treatment for different reason than PD, 11 pts are still on treatment. Grade (G) 3 adverse events (AEs) occurred in 22.7% of pts; the most common AEs were hand and foot syndrome (HFS) (G1 in 36.3% of pts, G2 18.1%, G3 4.5%), diarrhea (G1 31.8%, G2 18.1%), hypothyroidism (G1 9.09 %, G2 22.7 %), mucositis (G1 36.3%, G2 4,5%), and fatigue (G1 18.1%, G2 18.1%). Transitory withholding of cabo was observed in 63.6% of pts (14/22) and it was due to AEs in the 90% of the cases. For 5/22 pts (22.7 %), dose reduction was needed to manage AEs. The most common AEs leading to temporary drug interruption were HFS G1-3 (13.9%), liver disfunction G1-G2 (13.9%), diarrhea G1-G2 (11.6%), nausea and vomiting G2 (11.6 %) and fatigue G2 (9.3%). Conclusions: So far, the treatment with cabo after a I line anti-PD-1 based immunotherapy resulted active and well tolerated. Clinical trial information: NCT03463681 .

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.

scholarly journals Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study

2017 ◽  
Vol 35 (34) ◽  
pp. 3851-3858 ◽  
Author(s):  
Hans J. Hammers ◽  
Elizabeth R. Plimack ◽  
Jeffrey R. Infante ◽  
Brian I. Rini ◽  
David F. McDermott ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Antitumor Activity ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response Rate ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Safety And Efficacy

Purpose Combination treatment with immune checkpoint inhibitors has shown enhanced antitumor activity compared with monotherapy in tumor types such as melanoma. The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab plus ipilimumab in combination, and nivolumab plus a tyrosine kinase inhibitor in metastatic renal cell carcinoma (mRCC). Safety and efficacy results from the nivolumab plus ipilimumab arms of the study are presented. Patients and Methods Patients with mRCC received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3) every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks until progression or toxicity. End points included safety (primary), objective response rate, and overall survival (OS). Results All patients in the N3I3 arm (n = 6) were censored at the time of analysis as a result of dose-limiting toxicity or other reasons. Forty-seven patients were treated in both the N3I1 and the N1I3 arm, and baseline patient characteristics were balanced between arms. Grade 3 to 4 treatment-related adverse events were reported in 38.3% and 61.7% of the patients in the N3I1 and N1I3 arms, respectively. At a median follow-up of 22.3 months, the confirmed objective response rate was 40.4% in both arms, with ongoing responses in 42.1% and 36.8% of patients in the N3I1 and N1I3 arms, respectively. The 2-year OS was 67.3% and 69.6% in the N3I1 and N1I3 arms, respectively. Conclusion Nivolumab plus ipilimumab therapy demonstrated manageable safety, notable antitumor activity, and durable responses with promising OS in patients with mRCC.

Targeted Therapy for Metastatic Renal Cell Carcinoma

2006 ◽  
Vol 24 (35) ◽  
pp. 5601-5608 ◽  
Author(s):  
Robert J. Motzer ◽  
Ronald M. Bukowski
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Targeted Agents ◽  
Cell Renal Cell Carcinoma ◽  
Phase Ii And Iii ◽  
The Impact

The discovery of a relationship for the VHL tumor suppressor gene, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor in the growth of clear-cell renal cell carcinoma (RCC) has identified a pathway for novel targeted therapy. This study evaluated the impact of these agents on metastatic RCC (mRCC), and highlights recent phase II and III trials. A systematic review examined the clinical data for novel targeted agents in mRCC, with a focus on randomized phase II and III trials of the novel targeted agents sunitinib, temsirolimus, sorafenib, and bevacizumab. Several agents, including the small-molecule targeted inhibitors sunitinib, temsirolimus, sorafenib, and the monoclonal antibody bevacizumab, have demonstrated antitumor activity in randomized trials. Superior activity was found with sunitinib and temsirolimus versus cytokines in first-line therapy. Improved progression-free survival was reported with sorafenib and bevacizumab given second-line compared with placebo. Targeted therapies show promising activity in this disease, and they have been changing patient management. Sunitinib and sorafenib were recently approved by the US Food and Drug Administration for treatment of mRCC, These drugs are currently included in clinical practice.

Prognosis impact of serous metastases (SMs) in clear cell renal cell carcinoma patients in the GETUG-AFU-26 NIVOREN phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16566-e16566
Author(s):  
Florian Bardet ◽  
Cécile Dalban ◽  
Christine Chevreau ◽  
Sylvie Negrier ◽  
Brigitte Laguerre ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Objective Response ◽  
Prospective Trial ◽  
Prognostic Impact ◽  
Cell Renal Cell Carcinoma ◽  
Metastatic Sites

e16566 Background: Nivolumab monotherapy (N) is a standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies. IMDC criteria is the established prognostic model in anyline of systemic treatment including with N. While liver, bone and brain have been reported to convey a dismal prognosis, little is known about the pejorative prognostic impact of serous metastatic sites (pleura, peritoneum, pericardium) in patients receiving anti-PD (L) -1 treatment. Methods: We aimed to assess survival, and activity of N in patients included in the GETUG-AFU 26 NIVOREN phase II prospective trial ( NCT03013335 ), according to serous metastases (SMs). Results: Overall, 720 patients with metastatic ccRCC, and treated with N. Baseline RECIST metastases data were available for 708 patients included in this analysis. Among them, 142 (20%) had SMs (pleura, n=91 ; peritoneum, n=50 ; pericardium, n=1). Median PFS (4.5 vs 2.6 mo ; HR :1.31 ; p=0.0079), and OS (26.1 vs 15 mo ; HR :1.67 ; p<0.0001) were significantly lower in patients with SMs. The dismal prognostic impact was observed both with pleura and peritoneum SMs. These 2 sites were not significantly associated. Using multivariate Cox models, SMs remained significantly associated with poor survival, independently of IMDC category, gender, age, and number of previous lines of therapy. Objective response rate in patients with SMs was not significantly different from others patients (16.4 vs 22.1%; p=0.147). SMs were not statistically associated with known poor prognosis metastatic sites (cerebral, bone, and liver.) Conclusions: SMs are a strong independent prognostic impact in patients receiving N for metastatic ccRCC Poor prognostic metastatic sites should be considered when assessing the prognosis of patients with metastatic ccRCC

scholarly journals Low intratumor heterogeneity correlates with increased response to PD-1 blockade in renal cell carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097711
Author(s):  
Xia Ran ◽  
Jinyuan Xiao ◽  
Yi Zhang ◽  
Huajing Teng ◽  
Fang Cheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Simulated Data ◽  
The Cancer Genome Atlas ◽  
Intratumor Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Immune Activity

Background: Intratumor heterogeneity (ITH) has been shown to be inversely associated with immune infiltration in several cancers including clear cell renal cell carcinoma (ccRCC), but it remains unclear whether ITH is associated with response to immunotherapy (e.g. PD-1 blockade) in ccRCC. Methods: We quantified ITH using mutant-allele tumor heterogeneity, investigated the association of ITH with immune parameters in patients with ccRCC ( n = 336) as well as those with papillary RCC (pRCC, n = 280) from The Cancer Genome Atlas, and validations were conducted in patients with ccRCC from an independent cohort ( n = 152). The relationship between ITH and response to anti-PD-1 immunotherapy was explored in patients with metastatic ccRCC from a clinical trial of anti-PD-1 therapy ( n = 35), and validated in three equal-size simulated data sets ( n = 60) generated by random sampling with replacement based on this clinical trial cohort. Results: In ccRCC, low ITH was associated with better survival, more reductions in tumor burden, and clinical benefit of anti-PD-1 immunotherapy through modulating immune activity involving more neoantigens, elevated expression of HLA class I genes, and higher abundance of dendritic cells. Furthermore, we found that the association between the level of ITH and response to PD-1 blockade was independent of the mutation status of PBRM1 and that integrating both factors performed better than the individual predictors in predicting the benefit of anti-PD-1 immunotherapy in ccRCC patients. In pRCC, increased immune activity was also observed in low- versus high-ITH tumors, including higher neoantigen counts, increased abundance of monocytes, and decreased expression of PD-L1 and PD-L2. Conclusions: ITH may be helpful in the identification of patients who could benefit from PD-1 blockade in ccRCC, and even in pRCC where no genomic metrics has been found to correlate with response to immune checkpoint inhibitors.

scholarly journals Efficacy and Safety of Nivolumab and Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study

2021 ◽  
Vol 28 (2) ◽  
pp. 1402-1411
Author(s):  
Koji Iinuma ◽  
Koji Kameyama ◽  
Kei Kawada ◽  
Shota Fujimoto ◽  
Kimiaki Takagi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Efficacy And Safety ◽  
Lymphocyte Ratio

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

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