A phase III randomized open label study comparing bempegaldesleukin (NKTR-214) plus nivolumab to sunitinib or cabozantinib (investigator's choice) in patients with previously untreated advanced renal cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4595-TPS4595 ◽  
Author(s):  
Nizar M. Tannir ◽  
Neeraj Agarwal ◽  
Sumanta K. Pal ◽  
Maria Nirvana Formiga ◽  
Jun Guo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Combination Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Prognostic Score ◽  
Objective Response ◽  
Phase Iii ◽  
Open Label ◽  
Metastatic Rcc

TPS4595 Background: Bempegaldesleukin (NKTR-214) is a CD122-preferential IL-2 pathway agonist that stimulates proliferation and activation of tumor antigen-specific CD8+ T cells and natural killer cells within the tumor microenvironment and increases PD-1/PD-L1 expression. These properties make bempegaldesleukin (NKTR-214) a potentially promising agent for combination therapy with checkpoint inhibitors that target and inhibit the PD-1/PD-L1 pathway. In phase 1 studies, NKTR-214 plus nivolumab demonstrated encouraging objective response rates (ORR) in first-line renal cell carcinoma (RCC) and an acceptable safety profile. Immunotherapy with NKTR-214 plus nivolumab may lead to greater clinical benefit than tyrosine kinase inhibitors (TKIs), standard-of-care agents, in this patient population. Methods: This multicenter, randomized, open-label phase 3 study (NCT03729245) will evaluate the efficacy and safety of bempegaldesleukin (NKTR-214) plus nivolumab compared with investigator’s choice of TKI (sunitinib or cabozantinib) in patients with previously untreated advanced or metastatic RCC with clear cell component. Exclusion criteria include active brain metastasis and autoimmune disease. Approximately 600 patients will be randomized in a 1:1 ratio, stratified by PD-L1 status (≥1% vs < 1% or indeterminate), International Metastatic RCC Database Consortium prognostic score (1-2 [intermediate risk] vs 3-6 [poor risk]); and TKI (sunitinib or cabozantinib; cabozantinib percentage to be capped at 50%). Combination therapy will consist of bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenously (IV) every 3 weeks (Q3W) plus nivolumab 360 mg IV Q3W until progression or death or maximum of 2 years. TKI therapy will consist of sunitinib 50 mg orally once daily (QD) for 4 weeks followed by 2 weeks off or cabozantinib 60 mg orally QD. Primary objectives are ORR by blinded independent central radiology (BICR) assessment and overall survival. Secondary objectives are progression-free survival by BICR, safety, predictive value of PD-L1 expression, and quality of life. Enrollment is ongoing. Clinical trial information: NCT03729245.

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 .

Randomized Phase III Trial of Temsirolimus and Bevacizumab Versus Interferon Alfa and Bevacizumab in Metastatic Renal Cell Carcinoma: INTORACT Trial

2014 ◽  
Vol 32 (8) ◽  
pp. 752-759 ◽  
Author(s):  
Brian I. Rini ◽  
Joaquim Bellmunt ◽  
Jill Clancy ◽  
Kongming Wang ◽  
Andreas G. Niethammer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Combination Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Objective Response ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Cancer Center

PurposeTo prospectively determine the efficacy of combination therapy with temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in metastatic renal cell carcinoma (mRCC).Patients and MethodsIn a randomized, open-label, multicenter, phase III study, patients with previously untreated predominantly clear-cell mRCC were randomly assigned, stratified by prior nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to receive the combination of either temsirolimus (25 mg intravenously, weekly) or IFN (9 MIU subcutaneously thrice weekly) with bevacizumab (10 mg/kg intravenously, every 2 weeks). The primary end point was independently assessed progression-free survival (PFS).ResultsMedian PFS in patients treated with temsirolimus/bevacizumab (n = 400) versus IFN/bevacizumab (n = 391) was 9.1 and 9.3 months, respectively (hazard ratio [HR], 1.1; 95% CI, 0.9 to 1.3; P = .8). There were no significant differences in overall survival (25.8 ν 25.5 months; HR, 1.0; P = .6) or objective response rate (27.0% ν 27.4%) with temsirolimus/bevacizumab versus IFN/bevacizumab, respectively. Patients receiving temsirolimus/bevacizumab reported significantly higher overall mean scores in the Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI) –15 and FKSI-Disease Related Symptoms subscale compared with IFN/bevacizumab (indicating improvement); however, no differences in global health outcome measures were observed. Treatment-emergent all-causality grade ≥ 3 adverse events more common (P < .001) with temsirolimus/bevacizumab were mucosal inflammation, stomatitis, hypophosphatemia, hyperglycemia, and hypercholesterolemia, whereas neutropenia was more common with IFN/bevacizumab. Incidence of pneumonitis with temsirolimus/bevacizumab was 4.8%, mostly grade 1 or 2.ConclusionTemsirolimus/bevacizumab combination therapy was not superior to IFN/bevacizumab for first-line treatment in clear-cell mRCC.

Validation of the lung immune prognostic index (LIPI) in patients with metastatic renal cell carcinoma treated with nivolumab in the GETUG-AFU 26 NIVOREN trial.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 735-735 ◽  
Author(s):  
Pernelle Lavaud ◽  
Cécile Dalban ◽  
Sylvie Negrier ◽  
Christine Chevreau ◽  
Gwenaelle Gravis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Prognostic Score ◽  
External Validation ◽  
Objective Response ◽  
Prognostic Index ◽  
Independent Prognostic Factor

735 Background: The Lung Immune Prognostic Index (LIPI) is a prognostic score combining pretreatment dNLR (neutrophils/ (leucocytes-neutrophils) and LDH correlated to immune checkpoint inhibitors (ICI) benefit in several advanced cancers. We aimed to correlate LIPI score with Nivolumab (N) benefit in metastatic clear cell renal cell carcinoma (mccRCC) patients. Methods: We investigated the LIPI score in the GETUG-AFU 26 NIVOREN phase II trial assessing the activity and safety of N after failure of upfront VEGF-targeted therapies. A dNLR ≥ 3 and LDH ≥ upper superior limit were analyzed for the LIPI, and patients were stratified into 3 groups (good (GG), intermediate (IG) and poor (PG)) (Mezquita et al, JAMA Oncol 2018). The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). Results: Overall, 619 pts were included. Median age was 64 years old, 22.1% pts had received more than 2 previous lines and IMDC risk groups were 18.3%, 56.5% and 25.0% for good/intermediate and poor risk respectively. Median (m) follow up was 23.7 months (mo). The mPFS with N was 4.0 mo and mOS was not reach. LIPI classified 364 pts (58.8%) as GG, 216 pts (34.9%) as IG and 39 pts (6.3%) as PG. The PFS and OS results are summarized in the Table. In multivariate analysis, LIPI score remains an independent prognostic factor after adjustment for sex, age, ECOG PS and IMDC. ORR did not seem to be influenced by the LIPI groups. Conclusions: We report for the first time that LIPI score is associated with PFS and OS in patients treated with N for mccRCC. LIPI score appears as an independent prognostic factor even after adjustment for established risk factors. External validation in a VEGF-targeted therapy cohort is ongoing and will contribute to evaluate the predictive value of LIPI in mccRCC.[Table: see text]

PIVOT-09: A phase III randomized open-label study of bempegaldesleukin (NKTR-214) plus nivolumab versus sunitinib or cabozantinib (investigator's choice) in patients with previously untreated advanced renal cell carcinoma (RCC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS763-TPS763 ◽  
Author(s):  
Nizar M. Tannir ◽  
Neeraj Agarwal ◽  
Sumanta K. Pal ◽  
Daniel C. Cho ◽  
Maria Formiga ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Prognostic Score ◽  
Immunosuppressive Agents ◽  
Objective Response ◽  
Interleukin 2 ◽  
Phase Iii ◽  
Open Label ◽  
Risk Population ◽  
Poor Risk ◽  
Metastatic Rcc

TPS763 Background: Bempegaldesleukin (BEMPEG; NKTR-214) is a first-in-class interleukin-2 (IL-2) receptor pathway agonist that activates and expands effector T cells and natural killer cells in the tumor microenvironment and increases tumor PD-L1 expression, making BEMPEG a promising agent for combination with immune checkpoint inhibitors. In a phase 1/2 study, BEMPEG plus nivolumab (NIVO) demonstrated an encouraging objective response rate (ORR) in first-line advanced RCC (46%) and a manageable safety profile. BEMPEG plus NIVO offers a potential novel immunooncology treatment option for patients with advanced RCC. Methods: A global, multicenter, randomized, open-label phase 3 study is evaluating the efficacy and safety of BEMPEG plus NIVO vs investigator’s choice of tyrosine kinase inhibitor (TKI; sunitinib [SUNI] or cabozantinib [CABO]) in patients with previously untreated advanced or metastatic RCC with a clear-cell component. Patients must not have had prior systemic therapy (including neoadjuvant, adjuvant or vaccine therapy) for RCC. Key exclusion criteria include active brain metastasis and autoimmune disease requiring systemic immunosuppressive agents. Approximately 600 patients will be randomized 1:1 to receive 0.006 mg/kg BEMPEG plus 360 mg NIVO intravenously every 3 weeks or TKI (50 mg SUNI [4 weeks on, 2 weeks off schedule] or 60 mg CABO; orally each day). Patients will be stratified by International Metastatic RCC Database Consortium (IMDC) prognostic score (0 [favorable risk] vs 1-2 [intermediate risk] vs 3-6 [poor risk]) and TKI choice (SUNI vs CABO). Primary objectives are ORR by blinded independent central review (BICR) and overall survival in the IMDC intermediate/poor risk population and the intention-to-treat (ITT) population. Secondary objectives are progression-free survival by BICR in the IMDC intermediate/poor risk population and the ITT population, safety, PD-L1 expression as a predictive biomarker, and quality of life. Enrollment is ongoing. Clinical trial information: NCT03729245.

Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) (CaNI) for advanced renal cell carcinoma with variant histology (aRCCVH).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4592-TPS4592
Author(s):  
Bradley Alexander McGregor ◽  
Wanling Xie ◽  
Mehmet Asim Bilen ◽  
David A. Braun ◽  
Wenxin Xu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Phase Iii ◽  
Cancer Center ◽  
Prior Therapy ◽  
Variant Histology

TPS4592 Background: Despite advances in therapy of clear cell renal cell carcinoma, outcomes for patients with aRCCVH remain poor and these patients have typically been excluded from pivotal phase III studies. COSMIC-313 (NCT03937219) exploring C/N/I vs N/I excludes those with aRCCVH. Given responses seen with C as well as N/I in aRCCVH, there is reason to explore this triplet combination in this population. Methods: NCT04413123 is single arm phase 2 trial multi-institutional study involving Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Winship Cancer Institute, Karmanos Cancer Center, University of California in San Diego and University of Texas Southwestern. The primary objective is to assess the objective response rate (ORR) by investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 of C in combination with N/I in aRCCVH. Key secondary endpoints are progression-free survival (PFS), overall survival (OS) and toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 5. Mandatory pretreatment biopsy (unless medically infeasible) is required for correlative analysis to define the composition and transcriptional states of tumor and immune cells within the aRCCVH microenvironment in addition to determining the number and state of tumor-infiltrating T cell clones in aRCCVH and relation to response. Any variant histology is allowed, including clear-cell RCC with over 80% sarcomatoid features. Patients may be treatment naïve or received prior therapy including up to one anti-vascular endothelial growth factor agent not including C; prior therapy with immune checkpoint inhibitors is exclusionary. All International Metastatic RCC Database Consortium risk classifications are allowed; patients should have adequate organ function with performance status 0-1. C will be administered at a starting dose of 40 mg daily. N will be dosed at 3 mg/kg with I 1 mg/kg every 3 weeks followed by maintenance N 480 mg IV every 4 weeks and will be continued until progressive disease or unacceptable toxicity. C can be reduced to. 20 mg daily or 20 mg every other day as needed for toxicity. Dose reductions of N or I are not permitted but delays up to 12 weeks are allowed; N may be continued without I if toxicity can be directly attributed to I. Radiographic imaging is performed at baseline with first scheduled assessment at 12 weeks then every 8 weeks thereafter. A one-stage design is employed to enroll 40 eligible patients, which provides 93% power at 1-sided alpha of 0.09 to distinguish an ORR of 40% versus 20%. 12 or more responses are required to deem treatment promising. Seven of the planned 40 patients have been enrolled as of 2/1/2021. Clinical trial information: NCT04413123.

scholarly journals Modified Glasgow Prognostic Score associated with survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors

2021 ◽  
Vol 9 (7) ◽  
pp. e002851
Author(s):  
Jacqueline T Brown ◽  
Yuan Liu ◽  
Julie M Shabto ◽  
Dylan Martini ◽  
Deepak Ravindranathan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Glasgow Prognostic Score ◽  
Modified Glasgow Prognostic Score

BackgroundThe modified Glasgow Prognostic Score (mGPS) is a composite biomarker that uses albumin and C reactive protein (CRP). There are multiple immune checkpoint inhibitor (ICI)-based combinations approved for metastatic renal cell carcinoma (mRCC). We investigated the ability of mGPS to predict outcomes in patients with mRCC receiving ICI.MethodsWe retrospectively reviewed patients with mRCC treated with ICI as monotherapy or in combination at Winship Cancer Institute between 2015 and 2020. Overall survival (OS) and progression-free survival (PFS) were measured from the start date of ICI until death or clinical/radiographical progression, respectively. The baseline mGPS was defined as a summary score based on pre-ICI values with one point given for CRP>10 mg/L and/or albumin<3.5 g/dL, resulting in possible scores of 0, 1 and 2. If only albumin was low with a normal CRP, no points were awarded. Univariate analysis (UVA) and multivariate analysis (MVA) were carried out using Cox proportional hazard model. Outcomes were also assessed by Kaplan-Meier analysis.Results156 patients were included with a median follow-up 24.2 months. The median age was 64 years and 78% had clear cell histology. Baseline mGPS was 0 in 36%, 1 in 40% and 2 in 24% of patients. In UVA, a baseline mGPS of 2 was associated with shorter OS (HR 4.29, 95% CI 2.24 to 8.24, p<0.001) and PFS (HR 1.90, 95% CI 1.20 to 3.01, p=0.006) relative to a score of 0; this disparity in outcome based on baseline mGPS persisted in MVA. The respective median OS of patients with baseline mGPS of 0, 1 and 2 was 44.5 (95% CI 27.3 to not evaluable), 15.3 (95% CI 11.0 to 24.2) and 10 (95% CI 4.6 to 17.5) months (p<0.0001). The median PFS of these three cohorts was 6.7 (95% CI 3.6 to 13.1), 4.2 (95% CI 2.9 to 6.2) and 2.6 (95% CI 2.0 to 5.6), respectively (p=0.0216). The discrimination power of baseline mGPS to predict survival outcomes was comparable to the IMDC risk score based on Uno’s c-statistic (OS: 0.6312 vs 0.6102, PFS: 0.5752 vs 0.5533).ConclusionThe mGPS is prognostic in this cohort of patients with mRCC treated with ICI as monotherapy or in combination. These results warrant external and prospective validation.

scholarly journals Immune-Related Meningoencephalitis following Nivolumab in Metastatic Renal Cell Carcinoma

2021 ◽  
pp. 1051-1058
Author(s):  
Lisa B.E. Shields ◽  
Mohammad S. Alsorogi ◽  
Nataliya Mar ◽  
Arash Rezazadeh Kalebasty
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Rare Complication ◽  
Psoas Muscle ◽  
High Dose ◽  
Lower Extremity Weakness ◽  
Left Psoas Muscle ◽  
Metastatic Rcc

While immunotherapy with nivolumab is promising for patients with renal cell carcinoma (RCC), overactivation of the immune system can lead to serious side effects. Immune-related meningoencephalitis without a viral or microbial etiology is a rare complication that may occur in patients treated with checkpoint inhibitors (CPI). Herein, we report a 66-year-old man who underwent a partial nephrectomy which revealed a papillary RCC with clear cell component. Three years later, an abdomen and pelvic CT revealed metastatic lesions in the left psoas muscle and in the left 12th rib. The patient was treated with pazopanib which was discontinued after 2 weeks due to significant hepatic and renal toxicity. He subsequently started sunitinib. Two months later, a chest, abdomen, and pelvic CT demonstrated progressive metastatic RCC in the retroperitoneal mass of the left psoas muscle and paraspinal musculature as well as a left renal mass. The patient was treated with 7 cycles of the CPI nivolumab. He was subsequently hospitalized for 3 weeks after experiencing bilateral lower extremity weakness, lethargy, several falls, hyperthermia, confusion, and gait abnormalities. A CSF analysis demonstrated a lymphocyte pleocytosis with elevated protein and no bacterial or viral growth. The patient was treated with high-dose steroids after which his symptoms resolved. Chest, abdomen, and pelvic CT scans over the next 3 years revealed no evidence of metastatic disease, reflecting a progression-free survival of 40 months. We highlight the unique case of a patient with metastatic RCC who experienced immune-related meningoencephalitis following immunotherapy with nivolumab. Medical oncologists should be alert to the potential development of immune-related encephalitis in patients treated with nivolumab and should promptly diagnose and treat this concerning condition. The excellent oncologic outcome of this case emphasizes the need for continued aggressive measures for management of CNS toxicity resulting from CPI therapy.

scholarly journals Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial

2018 ◽  
Vol 36 (8) ◽  
pp. 757-764 ◽  
Author(s):  
David Cella ◽  
Bernard Escudier ◽  
Nizar M. Tannir ◽  
Thomas Powles ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Repeated Measures ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Renal Cell Carcinoma

Purpose In the phase III METEOR trial ( ClinicalTrials.gov identifier: NCT01865747), 658 previously treated patients with advanced renal cell carcinoma were randomly assigned 1:1 to receive cabozantinib or everolimus. The cabozantinib arm had improved progression-free survival, overall survival, and objective response rate compared with everolimus. Changes in quality of life (QoL), an exploratory end point, are reported here. Patients and Methods Patients completed the 19-item Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI-19) and the five-level EuroQol (EQ-5D-5L) questionnaires at baseline and throughout the study. The nine-item FKSI–Disease-Related Symptoms (FKSI-DRS), a subset of FKSI-19, was also investigated. Data were summarized descriptively and by repeated-measures analysis (for which a clinically relevant difference was an effect size ≥ 0.3). Time to deterioration (TTD) was defined as the earlier of date of death, radiographic progressive disease, or ≥ 4-point decrease from baseline in FKSI-DRS. Results The QoL questionnaire completion rates remained ≥ 75% through week 48 in each arm. There was no difference over time for FKSI-19 Total, FKSI-DRS, or EQ-5D data between the cabozantinib and everolimus arms. Among the individual FKSI-19 items, cabozantinib was associated with worse diarrhea and nausea; everolimus was associated with worse shortness of breath. These differences are consistent with the adverse event profile of each drug. Cabozantinib improved TTD overall, with a marked improvement in patients with bone metastases at baseline. Conclusion In patients with advanced renal cell carcinoma, relative to everolimus, cabozantinib generally maintained QoL to a similar extent. Compared with everolimus, cabozantinib extended TTD overall and markedly improved TTD in patients with bone metastases.

scholarly journals Phase III Trial of Bevacizumab Plus Interferon Alfa Versus Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Final Results of CALGB 90206

2010 ◽  
Vol 28 (13) ◽  
pp. 2137-2143 ◽  
Author(s):  
Brian I. Rini ◽  
Susan Halabi ◽  
Jonathan E. Rosenberg ◽  
Walter M. Stadler ◽  
Daniel A. Vaena ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Grade 3

Purpose Bevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-α) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-α versus IFN-α monotherapy was conducted. Patients and Methods Patients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-α (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-α monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety. Results Seven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-α and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-α monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-α. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-α. Patients who developed HTN on bevacizumab plus IFN-α had a significantly improved PFS and OS versus patients without HTN. Conclusion OS favored the bevacizumab plus IFN-α arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-α.

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