Outcomes with novel combinations in non-clear cell renal cell carcinoma(nccRCC): ORACLE study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4580-4580
Author(s):  
Deepak Kilari ◽  
Aniko Szabo ◽  
Pooja Ghatalia ◽  
Tracy L Rose ◽  
Nicole Weise ◽  
...  
Keyword(s):  
Clear Cell ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
New Combination ◽  
Clinical Activity ◽  
Cell Renal Cell Carcinoma ◽  
Clear Cell Rcc ◽  
Rhabdoid Differentiation

4580 Background: Despite advances in the treatment of clear cell RCC, there is a paucity of data to guide management of nccRCC due to the heterogeneity and rarity of these tumors. The clinical activity of new combination therapies (including immunotherapy (IO), anti-vascular endothelial growth factor inhibitors (VEGF), and mammalian target of rapamycin (mTOR) inhibitors) in metastatic nccRCC is not known. Methods: In this multicenter retrospective analysis, we explored the efficacy of combination systemic therapies in patients with nccRCC. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate (ORR) assessed by investigator review. Secondary endpoints include progression- free survival (PFS), disease control rate (DCR), median duration of response (DOR), overall survival (OS), and biomarker correlates. Results: Among 66 included patients, median age was 59 yr; 60% were male and 62% white. Histologies included papillary (38%), chromophobe (17%), unclassified (24%), translocation (12%), and other (9 %). Sarcomatoid and/or rhabdoid differentiation was present in 18%, 70% had prior nephrectomy, 86% were IMDC intermediate/poor risk, 29% and 32% had liver and bone metastasis respectively. 67% received combination treatment in the first line. Comparison of outcomes based on treatment regimen is shown in the table. Conclusions: Antitumor activity was observed with novel combinations in nccRCC which warrants further prospective studies. Response rates and survival with combination therapy in this dataset remain inferior to rates seen in clear cell RCC.[Table: see text]

scholarly journals Characteristics and Treatment Challenges of Non-Clear Cell Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3807
Author(s):  
Pierangela Sepe ◽  
Arianna Ottini ◽  
Chiara Carlotta Pircher ◽  
Andrea Franza ◽  
Melanie Claps ◽  
...  
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Case Reports ◽  
Treatment Options ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Mtor Inhibitors ◽  
Cell Renal Cell Carcinoma ◽  
Clear Cell Rcc

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

Phase III, placebo-controlled trial (SUCCEED) evaluating ridaforolimus as maintenance therapy in advanced sarcoma patients following clinical benefit from prior standard cytotoxic chemotherapy: Long-term (≥ 24 months) overall survival results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10010-10010 ◽  
Author(s):  
Jean-Yves Blay ◽  
Sant P. Chawla ◽  
Isabelle Ray-Coquard ◽  
Axel Le Cesne ◽  
Arthur P. Staddon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Controlled Trial ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Phase Iii ◽  
Clinical Activity ◽  
Prior Chemotherapy

10010 Background: The mammalian target of rapamycin (mTOR) regulates cell growth and proliferation and is abnormally activated in many sarcomas. Ridaforolimus, an oral mTOR inhibitor, demonstrated clinical activity in previous nonrandomized trials in advanced sarcomas following failure of prior chemotherapy. Methods: An international, multicenter, placebo-controlled, phase 3 trial was conducted to evaluate maintenance therapy with ridaforolimus in patients with metastatic soft-tissue or bone sarcomas who achieved disease control from prior chemotherapy. Patients were randomized (1:1) to receive oral ridaforolimus (40 mg) or placebo once daily for 5 days each week. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety and tolerability. For OS, patients were to be followed at 3-month intervals for at least 24 months and up to 60 months after randomization. Results: 702 of 711 randomized patients received treatment. At the time of the data cutoff for OS (386 deaths), patients in the study population had been followed for at least 15 months. Median OS was 93.3 weeks with ridaforolimus vs 83.4 weeks with placebo (hazard ratio [HR]=0.88; 95% confidence interval [CI]: 0.72, 1.08; P=0.23). Ridaforolimus significantly improved PFS vs placebo (HR=0.72; 95% CI: 0.61, 0.85; P=0.0001; median PFS: 17.7 weeks vs 14.6 weeks); PFS improved across all prespecified baseline characteristics. As expected from the class of mTOR inhibitors, the most common adverse events with ridaforolimus were stomatitis, thrombocytopenia, noninfectious pneumonitis, hypertriglyceridemia, hyperglycemia, infections, and rash. Conclusions: Oral ridaforolimus was generally well-tolerated and significantly improved PFS in metastatic sarcoma patients with benefit from prior chemotherapy, offering an effective treatment alternative to surveillance alone. Results of a long-term OS analysis (prespecified to occur at 67% mortality, 24 months minimum follow-up) in the intent-to-treat population will be available in early 2012.

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

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.

Treatment outcome for metastatic papillary and chromophobe renal cell carcinoma (RCC) patients treated with tyrosine-kinase inhibitors (TKIs) sunitinib and sorafenib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5037-5037 ◽  
Author(s):  
A. Plantade ◽  
T. Choueiri ◽  
B. Escudier ◽  
B. Rini ◽  
S. Negrier ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Clinical Activity ◽  
Exact Test ◽  
Entire Cohort ◽  
Number Of Patients ◽  
Clear Cell Rcc ◽  
Tki Treatment

5037 Background: Sunitinib (SUNI) and sorafenib (SORAF) are novel TKIs that have shown significant clinical activity in metastatic clear-cell RCC. Papillary (PAP) and chromophobe (CHRM) histologies represent the majority non-clear-cell RCC. The activity of SUNI and SORAF in non-clear cell histologies has not been evaluated. Methods: Clinical features at study entry and treatment outcomes were evaluated in all patients (pts) with metastatic PAP and CHRM RCC who received either SUNI or SORAF as their initial TKI treatment at one of five different cancer centers in France and USA between 2002 and 2006. Descriptive statistics were used to evaluate the collected data. Overall Response rate (ORR) was investigator-assessed per RECIST criteria. Fisher’s exact test was used for categorical variables and the Kaplan-Meier method was used to estimate survival (Overall Survival (OS) and progression-free survival (PFS)). Results: Median age for the 53 patients was 59 years and 64% were male. The number of patients with PAP and CHRM histologies were 41 (77%) and 12 (23%), respectively. Nephrectomy was performed in 87% of patients and 33/53 (62%) of pts were previously treated (26/33, 79%, with cytokines). ORR, PFS and OS for the entire cohort were 10%, 8.9 months (m) and 12.2 m, respectively. Twenty (38%) and 33 (62%) pts were treated with SUNI and SORAF, respectively. 3/12 (25%) of CHRM pts had an ORR vs. 2/41(4.8%) with PAP histology (P=0.07). PFS for CHRM pts was 9.3 m compared to 6.6 m for PAP pts (p=0.07). OS was not different across histologies and type of TKI received. SUNI treated pts had an ORR of 15% and PFS of 11.9 m compared to 6% (p=0.3) and 5.5 m for SORAF pts (p=0.002), respectively. Other factors found to be associated with shorter PFS include ECOG PS >0 (p=0.03) and hemoglobin< normal (p=0.02). Conclusions: TKI may have activity in metastatic CHRM RCC, similar to what is seen in clear-cell histology. Minimal activity however is noted in PAP RCC, justifying continued investigations of novel agents in this histology. No significant financial relationships to disclose.

A phase III, randomized, controlled study to compare tivozanib with sorafenib in patients (pts) with advanced renal cell carcinoma (RCC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 310-310 ◽  
Author(s):  
R. J. Motzer ◽  
P. Bhargava ◽  
B. Esteves ◽  
M. Al-Adhami ◽  
W. Slichenmyer ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Clear Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Vegf Receptor ◽  
Randomized Controlled ◽  
Long Term Treatment ◽  
Clear Cell Rcc

310 Background: Drugs that block vascular endothelial growth factor (VEGF) pathway signaling, such as the tyrosine kinase inhibitor sorafenib, have become standard treatment for pts with RCC. Tivozanib (AV-951) is a potent, selective small-molecule pan-VEGF receptor (VEGFR) inhibitor, with activity against the VEGFR-1, -2, and -3 kinases at subnanomolar concentrations. Preliminary results from a phase II randomized discontinuation trial of tivozanib (1.5 mg/d; 3 wks on, 1 wk off) in pts with RCC demonstrated an objective response rate (ORR) of 27% and a median progression-free survival (PFS) of 11.8 mo by independent radiology review, with a favorable safety profile. Patients with clear cell RCC who had undergone nephrectomy had an ORR of 32% and median PFS of 14.8 mo (Bhargava, et al. ASCO 2010. Abstract 4599). Based on this antitumor activity a phase III, randomized, controlled, global, multicenter trial is currently in progress to compare tivozanib with sorafenib in pts with advanced RCC. Methods: Approximately 500 adults with clear cell RCC who have undergone nephrectomy and received ≤ 1 prior systemic treatment (no prior VEGF-targeted therapy) were randomized 1:1 to treatment with tivozanib or sorafenib. Pts are receiving 1.5 mg/d tivozanib orally in 4-week cycles (3 wks on, 1 wk off) or continuous 400 mg sorafenib orally twice daily. The primary endpoint will be PFS by independent radiology review; secondary endpoints will include overall survival, ORR, and duration of response. Safety is being monitored through adverse event reporting and laboratory analyses; toxicities are graded using the NCI Common Terminology Criteria for Adverse Events, version 3.0. The effect of therapy on health-related quality of life will be compared between arms using kidney cancer-specific (FKSI-DRS), oncology (FACT-G), and general (EQ-5D) assessments. Pharmacokinetics and biomarker analyses will be performed. Results: Pending. Conclusions: Enrollment completed in August 2010. An ongoing extension study will allow access to tivozanib for pts who demonstrate progressive disease on sorafenib, as well as long-term treatment with tivozanib or sorafenib for pts who demonstrate clinical benefit. [Table: see text]

Outcomes of patients (pts) with metastatic non-clear-cell renal cell carcinoma (nccRCC) treated with pazopanib.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 456-456 ◽  
Author(s):  
Marc Ryan Matrana ◽  
Ali Baiomy ◽  
Khaled M. Elsayes ◽  
Aditya Shetty ◽  
Purnima Sravanti Teegavarapu ◽  
...  
Keyword(s):  
Platelet Count ◽  
Clear Cell ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Albumin Level ◽  
Cell Renal Cell Carcinoma ◽  
Cox Models ◽  
Normal Platelet Count ◽  
Normal Platelet

456 Background: Pazopanib prolongs progression-free survival (PFS) in treatment-naive and cytokine-refractory metastatic clear-cell RCC. Outcomes and safety data with pazopanib in metastatic nccRCC are limited. Methods: We retrospectively reviewed records of metastatic nccRCC pts who received pazopanib in the frontline and salvage settings (11/2009-11/2011). Response was assessed by a blinded radiologist (RECIST v1.1). PFS and overall survival (OS) were estimated by Kaplan-Meier methods. Log rank tests and univariate Cox models were used to evaluate the associations of OS and PFS with pt characteristics. Results: 29 pts were identified (frontline, 9; salvage after PD with other targeted therapies, 20). Seven (24%) had papillary, 4 (14%) chromophobe, 5 (17%) unclassified, and 13 (45%) other subtypes. PFS, OS, and objective response rates (ORR) are shown in the table. Improved OS was associated with prior nephrectomy in frontline pts, and in salvage pts with younger age, non-white race, absence of bone metastases, normal platelet count, higher albumin level, KPS>80, and MSKCC good-risk disease. There were no significant associations between frontline pt characteristics and PFS, but improved PFS was associated with normal platelet count, KPS>80, lower LDH, and higher albumin level in the salvage setting. Common adverse events (AEs): fatigue (31%), elevated transaminases (24%), diarrhea (21%), nausea/vomiting (17%), anorexia (17%), hypothyroidism (7%), and hypertension exacerbation (7%); 83% of AEs were grade 1/2. Six (21%) discontinued therapy due to AEs. There were no treatment-related deaths. Conclusions: Pazopanib demonstrated efficacy in pts with metastatic nccRCC. Toxicity was mild/moderate and manageable. [Table: see text]

FRACTION (Fast Real-time Assessment of Combination Therapies in Immuno-Oncology)-gastric cancer (GC): A randomized, open-label, adaptive, phase 2 study of nivolumab in combination with other immuno-oncology (IO) agents in patients with advanced GC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4137-TPS4137 ◽  
Author(s):  
Praveen Aanur ◽  
Martin Gutierrez ◽  
Ronan Joseph Kelly ◽  
Jaffer A. Ajani ◽  
Geoffrey Yuyat Ku ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rapid Development ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
New Combination ◽  
Clinical Activity ◽  
Phase 2 ◽  
Open Label

TPS4137 Background: Nivolumab, a fully human IgG4 mAb that targets programmed death-1, alone and in combination with ipilimumab, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte antigen 4, has demonstrated encouraging clinical activity in patients with advanced GC. These data support the rationale that nivolumab in combination with other IO agents or targeted therapies may improve treatment outcomes in patients with advanced GC. Given the rapid development of novel IO agents, traditional studies cannot efficiently evaluate all possible IO-IO and IO-targeted therapy combinations. FRACTION is an innovative clinical trial program with a rolling, adaptive platform design that allows for the addition of new combination regimens, as well as withdrawal of ineffective regimens. Here we describe the study concept, key design components, and the first IO treatment combinations of FRACTION-GC, a phase 2, randomized, open-label, adaptive study in advanced GC (NCT02935634). Methods: Patients with advanced GC or gastroesophageal junction (GEJ) cancer will be enrolled based on prior IO treatment and randomized to receive nivolumab plus BMS-986016 (fully human IgG4 mAb that targets lymphocyte activation gene 3) or nivolumab plus ipilimumab. Enrollment is continuous and may offer patients consecutive treatment options based on their treatment exposure and response. The primary endpoints are objective response rate, duration of response, and progression-free survival rate at 24 weeks. The secondary endpoint is safety. Comprehensive biomarker analyses will also be performed. New treatment combinations will be added over time to explore their potential benefits and to provide a continuous flow of treatment options for patients whose cancer progresses on existing treatments. In this way, FRACTION-GC is envisioned to accelerate the development of the next generation of IO combinations for patients with metastatic GC and GEJ cancer. Clinical trial information: NCT02935634.

First-line pembrolizumab (pembro) monotherapy in advanced clear cell renal cell carcinoma (ccRCC): Updated results for KEYNOTE-427 cohort A.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4570-4570 ◽  
Author(s):  
Scott S. Tykodi ◽  
Frede Donskov ◽  
Jae-Lyun Lee ◽  
Cezary Szczylik ◽  
Jahangeer Malik ◽  
...  
Keyword(s):  
Clear Cell ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Cell Renal Cell Carcinoma ◽  
Duration Of Response ◽  
Prior Systemic Therapy

4570 Background: KEYNOTE-427 (NCT02853344) is an open-label, single-arm, phase 2 study to evaluate efficacy and safety of first-line single-agent pembro, a programmed death 1 (PD-1) inhibitor, in patients (pts) with ccRCC (cohort A) and non–clear cell RCC (cohort B). Updated follow up from cohort A are presented. Methods: Pts with histologically confirmed ccRCC, measurable per RECIST v1.1, and no prior systemic therapy were eligible. Pts received pembro 200 mg IV Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or pt decision to withdraw. Primary end point was objective response rate (ORR; per RECIST v1.1 blinded independent central review). Additional end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: 110 pts enrolled; median (range) follow-up was 18.0 (2.5-22.7) mo. Median age (range) was 64 (29-87); 38.2%, 47.3%, and 14.5% had favorable, intermediate, and poor IMDC risk, respectively; 47.3% were PD-L1 positive. Confirmed ORR was 36.4% with 3 (2.7%) CRs and 37 (33.6%) PRs. Median DOR was not reached. Median PFS was 7.1 mo (95% CI, 5.6-11.0) and median OS was not reached. Results by IMDC category are outlined in the table. By PD-L1 status, confirmed ORR was 44.2% and 29.3% for positive and negative, respectively. By sarcomatoid differentiation (n=11), confirmed ORR was 63.6%. Treatment-related AEs occurred in 80.9%, with pruritus (28.2%) and fatigue (28.2%) most commonly reported. One pt died of treatment-related pneumonitis. Conclusions: With a median 18-months’ follow up, first-line pembro monotherapy continued to show antitumor activity in pts with ccRCC. Meaningful responses were observed in pts with intermediate/poor IMDC risk, PD-L1 positive and sarcomatoid differentiated tumors. Safety profile was comparable to previously reported. Clinical trial information: NCT02853344. [Table: see text]

Efficacy and safety of nivolumab in patients with non-clear cell renal cell carcinoma (RCC): Results from the phase IIIb/IV CheckMate 374 study.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 562-562 ◽  
Author(s):  
Nicholas J. Vogelzang ◽  
Joshua Jemison McFarlane ◽  
Mark D. Kochenderfer ◽  
Ana M. Molina ◽  
Edward Arrowsmith ◽  
...  
Keyword(s):  
Safety Profile ◽  
Clear Cell ◽  
Collecting Duct ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Histological Subtypes ◽  
Cell Renal Cell Carcinoma ◽  
Flat Dose

562 Background: Initial safety results from the phase 3b/4 CheckMate 374 study showed that flat-dose nivolumab (NIVO) at 240 mg every 2 wk (Q2W) had a consistent safety profile across patients (pts) with clear cell and non-clear cell advanced RCC. We report updated safety and first disclosure of efficacy for pts with non-clear cell RCC (nccRCC) in CheckMate 374. Methods: Eligible pts in this cohort were adults with advanced or metastatic nccRCC who received 0–3 prior systemic therapies. Pts received NIVO 240 mg IV Q2W for ≤24 mo or until confirmed progression, unacceptable toxicity, or withdrawal of consent. Pts who benefited after 24 mo continued treatment according to the standard of care. The primary endpoint was incidence of high-grade immune-mediated adverse events (IMAEs). Exploratory endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: In CheckMate 374, 44 pts had nccRCC. Histological subtypes included papillary (n = 24), chromophobe (n = 7), unclassified (n = 8), and other (n = 5). Most pts with nccRCC (66%) were treatment-naïve. After a median follow-up of 11.1 mo, median OS was 16.3 mo (95% confidence interval [CI] 9.2–not estimable [NE]). OS was similar regardless of baseline PD-L1 expression. ORR was 13.6% (95% CI 5.2–27.4). One pt had complete response (chromophobe histology) and 5 pts had partial response (2 pts with papillary and 1 pt each with chromophobe, collecting duct, and unclassified histology). Median DOR was 10.2 mo (95% CI 5.6–NE). Median PFS was 2.2 mo (95% CI 1.8–5.4). The 1-year PFS rate was 14% (95% CI 5–27). No new safety concerns were identified. No treatment-related grade 5 AEs or grade 3–4 IMAEs were reported. Conclusions: Clinically meaningful antitumor activity was observed in the first prospective study of NIVO monotherapy in nccRCC. Responses were observed in several histological subtypes. The safety profile of flat-dose NIVO at 240 IV Q2W is consistent with the initial outcomes reported from this study and across the NIVO program. Clinical trial information: NCT02596035.

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.

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