Clinical activity of PD1/PDL1 inhibitors in metastatic non-clear cell renal cell carcinoma (nccRCC).

482 Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinical parameters, overall response rate (ORR) by RECIST, time-to-treatment failure (TTF), and overall survival (OS) were summarized. Results: We identified 40 pts across 8 academic institutions. Fourteen (35%) had papillary histology, 10 (25%) chromophobe, 3 (8%) translocation, and 7 (18%) unclassified. Six (16%) had ccRCC with a sarcomatoid component > 30%. 20% had International Metastatic RCC Database Consortium (IMDC) favorable-risk disease, 60% intermediate, and 20% poor-risk. Ten (25%) were treatment-naïve and the majority received PD1/PDL1 monotherapy (n=30, 75%), while the remaining received a combination of PD1/PDL1 with anti-VEGF(R) or anti-CTLA4 therapy. ORR for the total cohort was 18% and 10% for PD1/PDL1 monotherapy pts (Table). With a median follow-up of 5.6 months, the overall median TTF was 4.7 months (2.9-15.9) and six-month OS was 81% (60-91%). Conclusions: PD1/PDL1 blockade resulted in some activity in pts with various nccRCC histologies. In the absence of available clinical trials, this data may support the use of PD1/PDL1 blocking agents in pts with nccRCC. [Table: see text]

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Implications of Programmed Death Ligand-1 Positivity in Non-Clear Cell Renal Cell Carcinoma

Journal of Kidney Cancer and VHL ◽

10.15586/jkcvhl.2018.107 ◽

2018 ◽

Vol 5 (4) ◽

pp. 6-13 ◽

Cited By ~ 2

Author(s):

Juan Chipollini ◽

Mounsif Azizi ◽

Charles C Peyton ◽

Dominic H Tang ◽

Jasreman Dhillon ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Type I ◽

Cell Renal Cell Carcinoma ◽

Programmed Death Ligand 1 ◽

Programmed Death ◽

Papillary Type

The purpose of this study was to assess the prognostic value of programmed death ligand-1 (PD-L1) positivity in a non-clear cell renal cell carcinoma (non-ccRCC) cohort. PD-L1 expression was evaluated by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) specimens from 45 non-ccRCC patients with available tissue. PD-L1 positivity was defined as ?1% of staining. Histopathological characteristics and oncological outcomes were correlated to PD-L1 expression. Cancer-specific survival (CSS) and recurrence-free survival (RFS) stratified by PD-L1 status were estimated using the Kaplan–Meier method. Median age was 58 years and median follow-up was 40 months. Non-ccRCC subtypes included sarcomatoid (n = 9), rhabdoid (n = 6), medullary (n = 2), Xp11.2 translocation (n = 2), collecting duct (n = 1), papillary type I (n = 11), and papillary type II (n = 14). PD-L1 positivity was noted in nine (20%) patients. PD-L1 positivity was significantly associated with higher Fuhrman nuclear grade (P = 0.048) and perineural invasion (P = 0.043). Five-year CSS was 73.2 and 83% for PD-L1 positive and negative tumors, respectively (P = 0.47). Five-year RFS was 55.6 and 61.5% for PD-L1 positive and negative tumors, respectively (P = 0.58). PD-L1 was expressed in a fifth of non-ccRCC cases and was associated with adverse histopathologic features. Expression of biomarkers such PD-L1 may help better risk-stratify non-ccRCC patients to guide treatment decisions and follow-up strategies.

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666P Pembrolizumab (pembro) monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (ccRCC): Results after a minimum of 41 months of follow-up from KEYNOTE-427 cohort A

Annals of Oncology ◽

10.1016/j.annonc.2021.08.062 ◽

2021 ◽

Vol 32 ◽

pp. S691-S692

Author(s):

D.F. McDermott ◽

J-L. Lee ◽

G.A. Bjarnason ◽

J. Larkin ◽

R. Gafanov ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

First Line ◽

Cell Renal Cell Carcinoma ◽

First Line Therapy ◽

Line Therapy

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hERG1 potassium channel expression predicts survival in clear-cell renal cell carcinoma: A pilot study with a long-term follow up

European Urology Supplements ◽

10.1016/s1569-9056(19)33819-9 ◽

2019 ◽

Vol 18 (9) ◽

pp. e3357

Author(s):

E. Lastraioli ◽

R. Tellini ◽

A. Mari ◽

S. Pillozzi ◽

A. Fiore ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Pilot Study ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Channel Expression ◽

Long Term Follow Up

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Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma

Journal for ImmunoTherapy of Cancer ◽

10.1186/s40425-018-0319-9 ◽

2018 ◽

Vol 6 (1) ◽

Cited By ~ 61

Author(s):

Vadim S. Koshkin ◽

Pedro C. Barata ◽

Tian Zhang ◽

Daniel J. George ◽

Michael B. Atkins ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Clinical Activity ◽

Cell Renal Cell Carcinoma

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CLO19-035: Safety Profile and Adverse Events of Sunitinib as a First-Line Treatment for Advanced/Metastatic Clear-Cell Renal Cell Carcinoma: Pooled Analysis of Randomized Controlled Trials

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2018.7229 ◽

2019 ◽

Vol 17 (3.5) ◽

pp. CLO19-035

Author(s):

Tarek Haykal ◽

Babikir Kheiri ◽

Varun Samji ◽

Yazan Zayed ◽

Ragheed Al-Dulaimi ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Pooled Analysis ◽

Current Standard ◽

Cell Renal Cell Carcinoma ◽

Hand Foot Syndrome ◽

Treatment Naïve

Background: Metastatic clear-cell renal cell carcinoma (RCC) is largely incurable, and its treatment remains challenging. Sunitinib, a tyrosine kinase inhibitor, is one of the current standard-of-care options for treatment-naïve patients with metastatic RCC. Despite the proven efficacy of sunitinib, prolonged treatment with some tyrosine kinase inhibitors (TKIs) has been associated with significant adverse events (AEs). Therefore, we aimed to calculate the exact prevalence of all sunitinib-related AEs in a pooled analysis from all available randomized controlled trials (RCTs). Methods: A comprehensive electronic database search was conducted for all RCTs comparing the clinical outcomes and adverse events of sunitinib versus all other available treatments for treatment-naïve advanced/metastatic clear-cell renal cell carcinoma. We then calculated the pooled prevalence of the most common reported side effects of sunitinib. All statistical analyses were performed using R Statistical Software v3.4.0 (R Foundation, Vienna, Austria). Results: We included 8 RCTs, with a total of 4,106 patients. The mean age was 62, with 66.44% males. Any grade AEs were reported in 72% of patients with the following frequencies: fatigue, 44%; diarrhea, 38%; nausea, 31%; hand-foot syndrome, 30%; hypertension, 27%; dysgeusia, 25%; hypothyroidism, 25%; cconstipation, 20%; stomatitis, 20%; inflammation of the mucosa, 18%; dyspepsia, 16%; vomiting, 14%; rash, 12%; asthenia, 11%; and epistaxis, 10%. Grade 3 (severe) AEs were reported in 52% of patients with the following frequencies: hypertension, 9%; fatigue, 8%; hand-foot syndrome, 5%; asthenia, 5%; diarrhea, 4%; and inflammation of the mucosa, 2%. Laboratory abnormalities were also reported as follows: increased AST, 7%; increased lipase, 6%; neutropenia, 6%; thrombocytopenia, 6%; hypophosphatemia, 5%; lymphocytopenia, 5%; anemia, 4%; and leukopenia, 3%. Conclusion: Despite sunitinib being one of the current standard treatments for patients with metastatic/advanced clear-cell RCC, its safety profile is concerning, with a high prevalence of reported dangerous side effects. These findings underscore the importance of the emergence of newer drugs and treatment plans for patients with metastatic RCC, not only to achieve similar or better clinical outcomes but also to decrease the burden of adverse events.

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ASPEN: A randomized phase II trial of everolimus versus sunitinib in patients with metastatic non-clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps4590 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS4590-TPS4590

Author(s):

Andrew J. Armstrong ◽

Susan Halabi ◽

Tim Eisen ◽

Walter Michael Stadler ◽

Robert R Jones ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Case Series ◽

Progression Free Survival ◽

Clinical Activity ◽

Cell Renal Cell Carcinoma ◽

Therapeutic Decisions ◽

Undifferentiated Histology

TPS4590 Background: Currently no level 1 evidence exists to guide therapeutic decisions in patients with metastatic non-clear cell renal cell carcinoma. Case series and retrospective analyses suggest that strategies targeting either the VEGF or mTOR/TORC1 pathways have clinical activity in papillary, chromophobe, or poorly differentiated histologic subtypes. Methods: We are conducting an international, randomized phase 2 trial of patients with metastatic non-clear cell RCC; either papillary, chromophobe, or undifferentiated histology; any Motzer risk group; and who have had no prior systemic therapy. All patients contribute tissue to an international biorepository for correlative genomic, genetic, and protein biomarker studies, along with companion longitudinal plasma and urine angiome studies. Patients are randomized to either everolimus or sunitinib (1:1) at FDA approved dosing until progression. The primary endpoint is progression free survival. Trial status: Seventy-three out of a planned 108 subjects have been enrolled at the time of abstract submission: median age 64, 59 white, 10 black, 4 unknown race, and includes 42 papillary and 31 chromophobe/undifferentiated histologies, 49 men and 22 women. Accrual is anticipated to be completed by December 2013. Accrual distribution by country is currently 43 (USA), 27 (UK), and 3 (Canada). The first DSMB meeting was conducted after 40 subjects completed at least 6 months of therapy and concluded that there were no unexpected safety signals and that the study should proceed. Tissue (primary, some metastatic, urine, plasma, whole blood) has been collected on all patients to date through the Duke Center for Human Genetics Biorepository. Clinical trial information: NCT01108445.

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Efficacy and safety profile of sunitinib as a first line treatment for advanced/metastatic clear-cell renal cell carcinoma: Pooled analysis of randomized controlled trials.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16067 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16067-e16067

Author(s):

Tarek Haykal ◽

Varun Samji ◽

Yazan Zayed ◽

Ragheed Al-Dulaimi ◽

Inderdeep Gakhal ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Pooled Analysis ◽

Current Standard ◽

Cell Renal Cell Carcinoma ◽

Hand Foot Syndrome ◽

Treatment Naïve ◽

Grade 3

e16067 Background: Metastatic clear-cell renal cell carcinoma (RCC) is largely incurable, and its treatment remains challenging. Sunitinib, a tyrosine kinase inhibitor, is one of the current standard-of-care options for treatment-naïve patients with metastatic RCC. Despite the proven efficacy of Sunitinib, prolonged treatment with some tyrosine kinase inhibitors (TKIs) has been associated with significant adverse events (AEs). Therefore, we aimed to calculate the exact efficacy in addition to the prevalence of all AEs of Sunitinib in a pooled analysis from all available randomized controlled trials (RCTs). Methods: A comprehensive electronic database search was conducted for all RCTs comparing the clinical outcomes and adverse events of Sunitinib versus all other available treatments for treatment-naïve advanced/metastatic clear-cell renal cell carcinoma. We then calculated the pooled outcomes and prevalence of the most common reported side effects of Sunitinib. All statistical analyses were performed using R Statistical Software v3.4.0 (R Foundation, Vienna, Austria). Results: We included 8 RCTs, with a total of 4106 patients. The mean age was62, with 66.44% males.The efficacy of Sunitinib was reported as 3 main outcomes: Median progression free survival at 10.73 [7.76, 13.7] months, median overall survival at 23.28 [16.74, 29.81] months and the estimated objective response rate at 25[13, 37] %. Any grade AEs were reported in 72% of patients with the following frequencies: fatigue 44%, diarrhea 38%, nausea 31%, hand-foot syndrome 30%, hypertension 27%, dysgeusia 25%, hypothyroidism25%, constipation 20%, stomatitis 20%, inflammation of the mucosa 18%, dyspepsia 16%, vomiting 14%, rash 12%, asthenia 11%, and epistaxis10%.Grade 3&4 (severe) AEs were reported in 52% of patients with the following frequencies: hypertension 9%, fatigue 8%, hand-foot syndrome 5%, asthenia 5%, diarrhea 4%, and inflammation of the mucosa 2%. Conclusions: Despite Sunitinib being one of the current standard treatments for patients with metastatic/advanced clear-cell RCC, with well-described efficacy, its safety profile is still concerning with a significant prevalence of reported grade 3-4 AEs of 52% of the treated patients in the included RCTs. These findings underscore the importance of the emergence of newer drugs and treatment plans for patients with metastatic RCC, not only to achieve similar or better clinical outcomes but also to decrease the percentage of grade 3-4 AEs.

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