Systemic Analysis and Review of Nivolumab-ipilimumab Combination as a Rescue Strategy for Renal Cell Carcinoma After Treatment With Anti–PD-1/PD-L1 Therapy

Carril-Ajuria, Lucía; Lora, David; Carretero-González, Alberto; Martín-Soberón, Maricruz; Rioja, Patricia; Castellano, Daniel; Velasco, Guillermo

doi:10.1016/j.clgc.2020.10.004

Cited by 13 publications

(9 citation statements)

References 16 publications

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“…It is also of note that, in those real-world setting retrospective studies of ICI rechallenged mRCC, outcomes at first ICI seem rather substantial compared to historic data studies. eir results were pooled in a recent meta-analysis [21]. ose studies reported an ORR of 4% to 15% during nivolumab-ipilimumab salvage therapy, with a pooled ORR of 10% in the meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

“…is strategy seems to be reasonably safe [9][10][11] and has shown some efficacy according to nonrandomized studies in metastatic melanoma [12][13][14] or in non-small cell lung cancer (NSCLC) [15][16][17]. In mRCC, few retrospective and nonrandomized prospective studies showed a modest efficacy of ICI rechallenge [18][19][20][21]. However, most of them focused only on ICIs combination rechallenge and no prognostic factors of response were assessed.…”

Section: Introductionmentioning

confidence: 99%

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REchallenge of NIVOlumab (RENIVO) or Nivolumab-Ipilimumab in Metastatic Renal Cell Carcinoma: An Ambispective Multicenter Study

Vauchier

Auclin

Barthélémy

et al. 2022

Journal of Oncology

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Introduction. Immune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors. We assessed efficacy of ICI rechallenge and factors associated with better outcomes. Patients and Methods. This ambispective multicenter study included 45 mRCC patients rechallenged with nivolumab ± ipilimumab between 2014 and 2020. Primary endpoint was investigator-assessed best objective response rate (ORR) for ICI rechallenge (ICI-2). Factors associated with ICI-2 progression-free survival (PFS) were evaluated with multivariate Cox models. Results. ORR was 51% (n = 23) at first ICI therapy (ICI-1) and 16% (n = 7) for ICI-2. Median PFS was 11.4 months (95% CI, 9.8–23.5) and 3.5 months (95% CI, 2.8–9.7), and median overall survival was not reached (NR) (95% CI, 37.8–NR) and 24 months (95% CI, 9.9–NR) for ICI-1 and ICI-2, respectively. Factors associated with poorer ICI-2 PFS were a high number of metastatic sites, presence of liver metastases, use of an intervening treatment between ICI regimens, Eastern Cooperative Oncology Group performance status ≥2, and poor International Metastatic RCC Database Consortium score at ICI-2 start. Conversely, ICI-1 PFS >6 months was associated with better ICI-2 PFS. In multivariate analysis, there were only statistical trends toward better ICI-2 PFS in patients with ICI-1 PFS >6 months ( p = 0.07 ) and toward poorer ICI-2 PFS in patients who received a treatment between ICI regimens ( p = 0.07 ). Conclusion. Rechallenge with nivolumab-based ICI has some efficacy in mRCC. We identified various prognostic factors in univariate analysis but only statistical trends in multivariate analysis. Our findings bring new evidence on ICI rechallenge and preliminary but unique data that may help clinicians to select patients who will benefit from this strategy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

REchallenge of NIVOlumab (RENIVO) or Nivolumab-Ipilimumab in Metastatic Renal Cell Carcinoma: An Ambispective Multicenter Study

Vauchier

Auclin

Barthélémy

et al. 2022

Journal of Oncology

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“…Immune checkpoint inhibitors in particular have demonstrated remarkable success in treating many tumors [38,39]. For instance, PD-1 and PD-L1 inhibitors showed signi cant improvement in melanoma, non-small cell lung cancer kidney cancer and other solid malignancies [40,41]. Monoclonal antibodies directed against CTLA4, such as ipilimumab, presented signi cant clinical bene t for individuals with metastatic melanoma [42].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of RAB34 Associates With Tumor Aggressiveness and Immune Infiltration in Glioma

Hou¹,

Wan²,

Wang³

et al. 2021

Preprint

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Background: RAB34 is aberrantly expressed in various cancers and exhibits oncogenic properties. However, its function in glioma remains largely unclear. Herein, we investigated the clinical value and biological functions of RAB34 in glioma.Methods: In this study, we collected 697 RNA-seq data from The Cancer Genome Atlas (TCGA) dataset and 325 RNA-seq data from Chinese Glioma Genome Atlas (CGGA) dataset. CCK-8 and EdU assays were employed to assess cell proliferation ability. The transwell assay was utilized to explore cell migration and invasion capacities. Western blot coupled with qRT-PCR were employed to determine the protein, as well as RNA contents. The statistical analyses along with the graphical work were mainly implemented in the R software.Results: RAB34 expression was positively related to the glioma tumor grade, and predicted poor outcomes for glioma patients. RAB34 expression was significantly upregulated in classical and mesenchymal subtypes, and IDH wild-type gliomas. Additionally, RAB34 expression was regulated by promoter DNA methylation. Moreover, RAB34 expression was remarkably correlated with inflammatory activities, immune infiltration, and immune checkpoints in glioma. In vitro experiments demonstrated that inhibition of RAB34 restrained the growth, migration, as well as invasion of glioma cells, and reversed the epithelial-to-mesenchymal transition (EMT) process. Conclusion: Our findings established RAB34 as a novel progression-related biomarker and a possible immunotherapy target for glioma.

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“…To date, the only data on the use of NIVO + IPI after prior anti-PD-(L)1 failure are based on four non-randomized phase II trials that were presented at the ESMO 2019 (TITAN-RCC) and ASCO 2020 (FRACTION-RCC, OMNIVORE, and HCRN GU16-260) congresses [ 39 , 40 , 41 , 42 ]. The pooled analysis of the four studies ( n = 237 patients) confirmed a low response rate of 10.0% associated with 27.0% of grade ≥3 AEs [ 43 ]. Finally, a small retrospective study of 45 patients reported results of the combination of NIVO + IPI in second-line treatment post-anti-PD-1 alone or in combination and/or post-TKI: after a median follow-up of 12 months, the ORR was 20% and the median PFS was 4 months (0.8–19 months) [ 44 ].…”

Section: Pending Questions and Impact On Clinical Practicementioning

confidence: 96%

First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma: What Are the Most Appropriate Combination Therapies?

Vano

Ladoire

Elaidi

et al. 2021

Cancers

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The development of antiangiogenic treatments, followed by immune checkpoint inhibitors (ICI), has significantly changed the management of metastatic clear cell renal cell cancer. Several phase III trials show the superiority of combination therapy, dual immunotherapy (ICI-ICI) or ICI plus tyrosine kinase inhibitors (TKI) of the vascular endothelium growth factor (VEGF) over sunitinib monotherapy. The question is therefore what is the best combination for a given patient? A strategy based on the International Metastatic Database Consortium (IMDC) classification is currently recommended with pembrolizumab + axitinib, cabozantinib + nivolumab, and lenvatinib + pembrolizumab (for all patients) or nivolumab + ipilimumab (for patients with intermediate or poor risk), which are the first-line treatment standards of care. However, several issues remain unresolved and require further investigation, such as the PD-L1 status, the relevance of possible options based on the patient’s profile, and consideration of second-line and subsequent treatments.

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Systemic Analysis and Review of Nivolumab-ipilimumab Combination as a Rescue Strategy for Renal Cell Carcinoma After Treatment With Anti–PD-1/PD-L1 Therapy

Cited by 13 publications

References 16 publications

REchallenge of NIVOlumab (RENIVO) or Nivolumab-Ipilimumab in Metastatic Renal Cell Carcinoma: An Ambispective Multicenter Study

REchallenge of NIVOlumab (RENIVO) or Nivolumab-Ipilimumab in Metastatic Renal Cell Carcinoma: An Ambispective Multicenter Study

Overexpression of RAB34 Associates With Tumor Aggressiveness and Immune Infiltration in Glioma

First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma: What Are the Most Appropriate Combination Therapies?

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