Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy

Graham, Jeffrey; Wells, J.C.; Dudani, Shaan; Gan, Chun Loo; Donskov, Frede; Lee, Jae‐Lyun; Kollmannsberger, Christian; Meza, Luís; Beuselinck, Benoît; Hansen, Aaron Richard; North, Scott; Bjarnason, Georg A.; Sayegh, Nicolas; Kanesvaran, Ravindran; Wood, Lori; Hotte, Sébastien J.; McKay, Rana R.; Choueiri, Toni K.; Heng, Daniel Yick Chin

doi:10.1016/j.ejca.2022.05.002

Cited by 22 publications

(20 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, Procopio et al demonstrated the efficacy of cabozantinib in metastatic collecting duct carcinoma (CDC) [ 16 ]. The study prospectively enrolled patients for central pathology review and was a breakthrough for the treatment of nccRCC considering the rarity of disease and that the only prospective trial for CDC was dated 2007 and included patients treated with platinum-based chemotherapy [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab Plus Axitinib for Metastatic Papillary and Chromophobe Renal Cell Carcinoma: NEMESIA (Non Clear MEtaStatic Renal Cell Carcinoma Pembrolizumab Axitinib) Study, a Subgroup Analysis of I-RARE Observational Study (Meet-URO 23a)

Stellato

Buti

Maruzzo

et al. 2023

IJMS

View full text Add to dashboard Cite

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20–25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9/19 papillary, 5/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7–11.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Pembrolizumab Plus Axitinib for Metastatic Papillary and Chromophobe Renal Cell Carcinoma: NEMESIA (Non Clear MEtaStatic Renal Cell Carcinoma Pembrolizumab Axitinib) Study, a Subgroup Analysis of I-RARE Observational Study (Meet-URO 23a)

Stellato

Buti

Maruzzo

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Results from the IMDC have further supported the clinical benefit of IO-based therapy in patients with nccRCC. 22…”

Section: Discussionmentioning

confidence: 99%

“…Results from the IMDC have further supported the clinical benefit of IO-based therapy in patients with nccRCC. 22 Sarcomatoid dedifferentiation is known to be one of the most aggressive phenotypes of mRCC, which portends poor survival outcomes. [23][24][25] Recently, sarcomatoid components have been reported to display increased programmed death ligand-1 (PD-L1) expression, and thus likely have an increased treatment response to IO agents that target the high levels of PD-L1.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Patients With Metastatic Renal Cell Carcinoma Experiencing Complete Response to First-line Therapies: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

et al. 2023

Self Cite

View full text Add to dashboard Cite

Purpose:Clinical trials have demonstrated higher complete response rates in the immuno-oncology–based combination arms than in the tyrosine kinase inhibitor arms in patients with metastatic renal cell carcinoma. We aimed to characterize real-world patients who experienced complete response to the contemporary first-line therapies.Materials and Methods:Using the International Metastatic Renal Cell Carcinoma Database Consortium, response-evaluable patients who received frontline immuno-oncology–based combination therapy or tyrosine kinase inhibitor monotherapy were analyzed. Baseline characteristics of patients and post-landmark overall survival were compared based on best overall response, as per RECIST 1.1.Results:A total of 52 (4.6%) of 1,126 and 223 (3.0%) of 7,557 patients experienced complete response to immuno-oncology–based and tyrosine kinase inhibitor therapies, respectively (P = .005). An adjusted odds ratio for complete response achieved by immuno-oncology–based combination therapy (vs tyrosine kinase inhibitor monotherapy) was 1.56 (95% CI 1.11-2.17; P = .009). Among patients who experienced complete response, the immuno-oncology–based cohort had a higher proportion of non–clear cell histology (15.9% and 4.7%; P = .016), sarcomatoid dedifferentiation (29.8% and 13.5%; P = .014), and multiple sites of metastases (80.4% and 50.0%; P < .001) than the tyrosine kinase inhibitor cohort. Complete response was independently associated with post-landmark overall survival benefit in both the immuno-oncology–based and tyrosine kinase inhibitor cohorts, giving respective adjusted hazard ratios of 0.17 (95% CI 0.04-0.72; P = .016) and 0.28 (95% CI 0.21-0.38; P < .001).Conclusions:The complete response rate was not as high in the real-world population as in the clinical trial population. Among those who experienced complete response, several adverse clinicopathological features were more frequently observed in the immuno-oncology–based cohort than in the tyrosine kinase inhibitor cohort. Complete response was an indicator of favorable overall survival.

show abstract

“…Compared with the era of cytokines, obvious improvements in patients’ lifetimes have been obtained with VEGF receptor inhibitors; nevertheless, results from several clinical trials testing the efficacy of sunitinib or sorafenib suggest that the response rate and survival benefit of patients with PRCC are markedly inferior to that of patients with clear cell renal cell carcinoma, probably due to the disparate genetic background [ 36 , 37 , 38 ]. In addition, MET inhibitors and immune checkpoint blockers (cabozantinib and nivolumab, for instance) are also feasible for metastatic PRCC patients, displaying a higher responsivity than VEGF receptor inhibitors on the whole [ 39 , 40 ]. Despite these ameliorations, the overall clinical outcome of patients diagnosed with advanced PRCC is far from satisfactory, and most of them eventually die after suffering all kinds of treatment strategies, putting an insufferable financial burden on their families [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Five Tumor Antigens for Development and Two Immune Subtypes for Personalized Medicine of mRNA Vaccines in Papillary Renal Cell Carcinoma

Yuan

Jiang³

2023

JPM

View full text Add to dashboard Cite

Increasing evidence has revealed the promise of mRNA-type cancer vaccines as a new direction for cancer immune treatment in several solid tumors, however, its application in papillary renal cell carcinoma (PRCC) remains unclear. The purpose of this study was to identify potential tumor antigens and robust immune subtypes for the development and appropriate use of anti-PRCC mRNA vaccines, respectively. Raw sequencing data and clinical information of PRCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The cBioPortal was utilized for the visualization and comparison of genetic alterations. The TIMER was used to assess the correlation between preliminary tumor antigens and the abundance of infiltrated antigen presenting cells (APCs). Immune subtypes were determined by the consensus clustering algorithm, and clinical and molecular discrepancies were further explored for a deeper understanding of immune subtypes. Five tumor antigens, including ALOX15B, HS3ST2, PIGR, ZMYND15 and LIMK1, were identified for PRCC, which were correlated with patients’ prognoses and infiltration levels of APCs. Two immune subtypes (IS1 and IS2) were disclosed with obviously distinct clinical and molecular characteristics. Compared with IS2, IS1 exhibited a significantly immune-suppressive phenotype, which largely weakened the efficacy of the mRNA vaccine. Overall, our study provides some insights for the design of anti-PRCC mRNA vaccines and, more importantly, the selection of suitable patients to be vaccinated.

show abstract

Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy

Cited by 22 publications

References 20 publications

Pembrolizumab Plus Axitinib for Metastatic Papillary and Chromophobe Renal Cell Carcinoma: NEMESIA (Non Clear MEtaStatic Renal Cell Carcinoma Pembrolizumab Axitinib) Study, a Subgroup Analysis of I-RARE Observational Study (Meet-URO 23a)

Pembrolizumab Plus Axitinib for Metastatic Papillary and Chromophobe Renal Cell Carcinoma: NEMESIA (Non Clear MEtaStatic Renal Cell Carcinoma Pembrolizumab Axitinib) Study, a Subgroup Analysis of I-RARE Observational Study (Meet-URO 23a)

Characterization of Patients With Metastatic Renal Cell Carcinoma Experiencing Complete Response to First-line Therapies: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

Identification of Five Tumor Antigens for Development and Two Immune Subtypes for Personalized Medicine of mRNA Vaccines in Papillary Renal Cell Carcinoma

Contact Info

Product

Resources

About