Clinical outcomes model in renal cell cancer patients treated with modified vaccinia Ankara plus tumor-associated antigen 5T4

2015 ◽  
Vol 30 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Robert J. Amato ◽  
Youxin Xiong ◽  
Hui Peng ◽  
Virginia Mohlere
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Elispot Response ◽  
Ecog Performance Status ◽  
Fuhrman Grade ◽  
Phase Ii Studies

Aims We developed an outcomes model to select patients for renal cell cancer vaccine immunotherapy. Materials and methods We examined clinical data from 2 phase II studies of modified vaccinia Ankara as vector to express 5T4 (MVA-5T4), calculated progression-free survival (PFS) and overall survival (OS), and created risk groups based on the number of factors involved. Results Median OS was 12.4 months; median PFS was 3.6 months. Significant factors (p<0.05) included neutrophils (both), bone metastases (OS), ECOG performance status (OS), lactate dehydrogenase levels (both), prior therapy with tyrosine kinase inhibitors plus immunotherapy (OS), Fuhrman grade (OS), and 5T4-specific ELISPOT response (PFS). By group, median OS was not reached in patients with favorable risk (censored at cutoff), was 13.7 months in those with intermediate risk and 4.0 months in those with poor risk. Conclusions Further validation of this model will identify the patients most likely to respond to MVA-5T4 and provide a framework for outcomes models for other vaccine therapies.

Phase Ib safety trial of CVX-060, an intravenous humanized monoclonal CovX body inhibiting angiopoietin 2 (Ang-2), with axitinib in patients with previously treated metastatic renal cell cancer (RCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2533-2533
Author(s):  
Ashwin Gollerkeri ◽  
Michael S. Gordon ◽  
John M. Burke ◽  
Ralph Hauke ◽  
Jiri Tomasek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Cell Cancer ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Prior Therapy

2533 Background: PF-04856884 is a recombinant humanized monoclonal antibody fused to two Ang-2 binding peptides. Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factors (VEGFs) that is approved for patients (pts) with advanced renal cell cancer who failed 1 prior therapy. Metastatic RCC (mRCC) is an angiogenic tumor sensitive to VEGF tyrosine kinase inhibitors. Resistance to VEGF targeted therapy may be mediated by Ang-2. Methods: In Part I (safety lead in) of the study, the primary endpoint was treatment related dose limiting toxicities (DLT) in pts with mRCC who had received 1-3 prior treatments. Pts received PF-04856884 (15 mg/kg/week) plus axitinib (5 mg BID) for 4 week cycles (the recommended Phase II dose of each) and were assessed for DLT, PK, and potential predictive biomarkers (Ang-2 and VEGF-A). For Part II (Phase II portion), pts with mRCC who had received 1 prior anti-VEGF agent were to be randomized to PF-04856884 + axitinib or axitinib alone to assess median progression free survival. Results: Part I enrolled 18 pts with median age of 62.5 years (39-82), and ECOG performance status of 0-1. One pt had a DLT of Grade 4 pulmonary embolism (PE). Most common related AEs: anorexia in 10 pts (56%), diarrhea 8 (44%), fatigue 8 (44%), nausea 7 (39%), hypertension 6 (33%) and vomiting 6 (33%). Treatment-related thromboembolic events (TEEs) were observed: PE in 2 pts (11%), and cerebrovascular accident (CVA), presumed bowel ischemia, and possible cardiac chest pain in 1 pt (6%) each. One pt had Grade 2 venous thrombosis unrelated to either treatment. Due to the reported TEE, PF-04856884 was reduced to 10 mg/kg in pts remaining on study and enrollment to Part II was not initiated. No significant PK interaction was observed. Two pts had partial response (PR) and 1 pt had unconfirmed PR. Twelve pts (66%) remained on study ≥91 days with a median duration of 120 days (8-279). Anti-PF-04856884 antibody results are not available. Conclusions: Due to the higher than expected TEEs, alternate doses of PF-04856884 and/or disease settings are being considered. Clinical trial information: NCT01441414.

Lymphopenia and clinical outcome of elderly patients treated with sunitinib for metastatic renal cell cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15615-e15615
Author(s):  
Ugo De Giorgi ◽  
Karim Rihawi ◽  
Michele Aieta ◽  
Giovanni Lo Re ◽  
Teodoro Sava ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Elderly Patients ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Metastatic Renal Cell Cancer ◽  
Grade 3

e15615 Background: Lymphopenia is associated with toxicity and outcome in several cancer types. We assessed the association of pre-treatment lymphopenia with toxicity and clinical outcome of elderly patients with metastatic renal cell cancer treated with first-line sunitinib. We evaluated the prognostic factors in these patients. Methods: We reviewed the clinical files of 181 patients aged >70 years with mRCC treated with first-line sunitinib in seventeen Italian Oncology Units from February 2006 to September 2011. Baseline lymphopenia was defined as lymphocyte counts <1,000/µL. Results: Twenty–nine patients (16.0%) had a baseline lymphocyte counts <1,000/µL, and 152 (84%) ≥1,000/µL. No difference between the two groups was reported in overall response rate (p = 0.207), dose reductions (p = 0.740); discontinuations due to adverse events (p = 0.175), overall incidence of grade 3-4 toxicities (p = 0.112) even if more patients in the group with lymphopenia had grade 3-4 neutropenia (p = 0.017), grade 3-4 thrombocytopenia (p = 0.017) and grade 3-4 diarrhea (p = 0.006). In multivariate analysis, performance status and Heng score were predictors of progression-free survival (p = 0.015 and p = 0.0006, respectively), while performance status, Heng score, and lymphopenia were found to be significantly associated with overall survival (p = 0.007, p < 0.0001 and p = 0.023, respectively). Conclusions: Sunitinib appeared safe and active in elderly patients with lymphopenia. Lymphocyte counts is an independent prognostic factor for OS in elderly patients with mRCC treated with first-line sunitinib.

Safety and efficacy of axitinib in pretreated patients with metastatic renal cell carcinoma: A single center experience of the Medical University of Vienna, Austria.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15535-e15535
Author(s):  
Ursula Maria Vogl ◽  
Lothar Ponhold ◽  
Gottfried J Locker ◽  
Christoph Zielinski ◽  
Christoph Klingler ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Second Line ◽  
Ecog Performance Status ◽  
Single Center Experience ◽  
Metastatic Sites

e15535 Background: Axitinib is a highly selective inhibitor of VEGFR-1, 2 and 3 and has recently been approved for second-line treatment of metastatic renal cell cancer (mRCC). We present data of 43 patients treated with axitinib in second-line and beyond. Methods: Medical records of all patients who were treated with axitinib between July 2009 and December 2012 were retrospectively reviewed. Axitinib was prescribed at a dose of 5 mg bid and escalated to 7 or 10 mg bid in the absence of hypertension and other dose-limiting toxicities. Objective response rate (ORR) was assessed by RECIST. Progression free survival (PFS) and overall survival (OS) were calculated from the first day of axitinib until progression and/or death, respectively. Results: Fourty-three patients with a median age of 65 years (range: 17-84) are currently evaluable for analysis. The majority of patients (58.1%) had an ECOG Performance status of 0 and were classified MSKC- intermediate risk (62.8%). All patients had undergone surgery for the primary tumor and 53.5% had three or more metastatic sites. Fifty-five percent of the patients received axitinib in third or fourth-line (14% and 41.9%, respectively). Prior therapies included sunitinib (86%), everolimus (35%) and pazopanib (35%) and 62.8% had progressed on sunitinib before axitinib was initiated. Objective remission and disease stabilization were observed in 14.3% and 40% of the entire population. The median PFS and OS were 6.8 months (95% CI: 5.5 – 8.0) and 17.2 months (95% CI: 10.8 – 23.6), respectively. Dose escalation to 7 or 10 mg bid was feasible in 40% of the patients. Fatigue (76.7%), hypertension (65.1%) and hypothyroidism (53.5%) were among the most commonly observed all grade toxicities. Conclusions: Axitinib showed considerable efficacy in both second-line and beyond second-line patients. Generous dose escalation based on a “treat to hypertension”-concept may have led to a longer PFS than previously reported from a purely VEGFR-TKI-refractory patient population.

Demographics, response, and overall survival of patients with advanced renal cell cancer to sunitinib in a cohort of minority patient population

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16164-e16164
Author(s):  
M. Shah ◽  
S. Sreenivasappa ◽  
R. Kouz ◽  
B. Ciobanu ◽  
M. Mullane ◽  
...  
Keyword(s):  
Median Survival ◽  
Renal Cell Cancer ◽  
Survival Data ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Cell Cancer ◽  
Minority Population ◽  
Ecog Performance Status ◽  
Poor Risk

e16164 Background: Sunitinib is a tyrosine kinase inhibitor active in renal cell cancer (RCC). There is scanty literature of its efficacy in minority population. Methods: 21 patients (pts) with RCC who received sunitinib between February 2006-September 2007 were identified and studied as a retrospective cohort. Clinical and survival data were analyzed using fisher's test, chi square test, Kaplan Meier analyses. Results: Of the 21 patients, 11 (52%) were female and 10 (47%) male, 7 (33.3%) African American, 7 (33.3%) Hispanic, and 5 (23.8%) Caucasian. Median age at diagnosis was 59 years (32–74). 7 (33.3%) had clear cell and 3 (14.3%) sarcomatoid pathology. Mixed, poorly differentiated, papillary and unknown histology were 2 (9.5%) each. 12 (57%) pts had stage 4 disease at diagnosis, stage 3 in 3 (14.3%), stage 2 in 1 (4.8%) and 5 (23%) had missing data. 14(66.7%) pts underwent nephrectomy while 7 (33.3%) did not. 6 (28.6%) pts has good MSKCC risk score, 11 (52.4%) intermediate risk and 3 (14.3%) poor risk. Sunitinib was given at a dose of 50 mg daily for 4 wks followed by 2 wks off. Median duration of treatment was 2.5 months (0–9 mts) and median follow up was 13 mts (1–21 mts). Common grade 3–4 toxicities observed were hand foot syndrome (n = 2), hypertension (n = 2) and thrombocytopenia (n = 1). 4 pts discontinued therapy due to adverse events. 5 (23.8%) has stable disease and 13 (61.9%) had progressive disease. Response to sunitinib was not influenced by sex, race, performance status, MSKCC Score, serum calcium level, LDH and hemoglobin level. Median survival of the group was 4 mts with no difference based on gender (p = 0.8), ethnicity (p = 0.8) or histologic type (p = 0.7). Survival of pts with ECOG performance status (PS) 1 was 8 mts, PS 2 was 4 mts, PS 3 was 2 mts (p = 0.001), MSKCC good risk was 9.4 mts, intermediate score was 9.4 mts and poor risk was 2 mts (p = 0.18). Hemoglobin (p = 0.6), LDH (p = 0.6), calcium (p = 0.2) did not affect the survival. Conclusions: In this minority cohort of pts with RCC treated with sunitinib, response and median survival is much lower than the historical controls. Tolerability and side effect profile are similar to reported literature. Prospective studies are warranted in the treatment of RCC with sunitinib in ethnic minority population. No significant financial relationships to disclose.

Heterogeneity of intermediate prognosis patients (pts) with metastatic renal cell cancer (mRCC) treated with sunitinib.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 446-446
Author(s):  
Avishay Sella ◽  
M. Dror Michaelson ◽  
Ewa M. Matczak ◽  
Ronit Simantov ◽  
Mariajose Lechuga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kinase Inhibitors ◽  
Risk Model ◽  
Cox Regression ◽  
Performance Status ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Ecog Performance Status

446 Background: The Memorial Sloan Kettering Cancer Center risk model (MSKCC) stratifies pts with mRCC into 3 prognostic groups based on 5 risk factors. The Intermediate Prognosis (INTMP) risk group is characterized by the presence of 1 or 2 factors, equivalent to 15 possible distinct entities. This heterogeneity suggests that the efficacy of tyrosine kinase inhibitors may be less predictable in the INTMP than in the other groups. Methods: We identified 548 patients with INTMP mRCC from a pooled analysis of patients treated with sunitinib in 6 prospective phase II and III clinical trials. Statistical analysis was performed using Cox regression and Kaplan-Meier methods and Pearson chi-square tests. Results: Most INTMP pts were male (69%), with clear cell carcinoma (93%), good ECOG performance status (PS) (60.5% PS 0; 38% PS 1; 1.5% PS 2) and median age 60. There were 325 pts (56%) with 1risk factor, and the most common were <1 year from diagnosis (38%); low hemoglobin (Hg) (29%), or both (16%). Objective response rate (RR) was 35.4%, progression free survival (PFS) was 8.4 months (m) and overall survival (OS) was 20.5 m. The 325 (59.3%) pts with one risk factor fared better than the 223 (40.7%) patients with two: PFS 10.7 vs 6.5 m, HR 0.684(95% CI 0.563-0.832, p<0.001); OS 26.3 vs 14.1 m, HR 0.522 (95% CI 0.420-0.648, p<0.001). RR was similar (38.5% vs 30.9%, p=0.071). Sunitinib was more effective in pts with PS 0: PFS 9.7 vs 7.8 m, HR 0.797 (95% CI 0.654-0.972, p=0.0242); OS 24.7 vs 14.0 m, HR 0.529 (95% CI 0.426-0.657, p<0.001), RR 38.9% vs 30.1%, (p=0.036). The most common grade 3/4 adverse events (AE) were fatigue (17%), hypertension (10%), hand foot skin reaction (9%), and nausea (4%). Overall, 17% of patients discontinued due to AE, and the overall pattern of AEs did not vary among the subgroups. Conclusions: MSKCC INTMP is a heterogeneous group comprised mostly of pts with low Hg and/or < 1 year from diagnosis. PFS and OS are superior in pts with 1 vs. 2 risk factors, and PS is also an important factor in the INTMP group. Sunitinib is active and well-tolerated in INTMP pts. Clinical trial information: NCT00077974, NCT00083889, NCT00137423, NCT00267748, NCT00338884, NCT00054886.

Efficacy and toxicity of sunitinib in renal insufficiency patients with metastatic renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15573-e15573
Author(s):  
Ki Hyang Kim ◽  
Sun Young Rha ◽  
Ho Young Kim ◽  
Hye Ryun Kim ◽  
Jong-Mu Sun ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Renal Impairment ◽  
Renal Insufficiency ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Ecog Performance Status

e15573 Background: We investigated the efficacy and toxicity of sunitinib in renal insufficiency patients with metastatic renal cell carcinoma (mRCC). Methods: From Korean Renal Cell Cancer Registry (KRCCR, http://kcsg-rcc.or.kr), we searched renal insufficiency patients with mRCC treated with sunitinib as a first-line treatment between January 2008 and May 2012. The Crockcroft-Gault formula was used for calculation of glomerular filtration rate and selected patients with chronic renal failure not requiring dialysis. Patients characteristics, clinical outcomes, toxicities were evaluated. The patients were divided by 2 groups based on the National Kidney Foundation definition of renal impairment and overall survival (OS) and progression-free survival (PFS) were obtained. Results: From total 997 enrolled from KRCCR, 34 patients were evaluated. Patients characteristics included: median age 66 years, ECOG performance status of 0 and 1 were 90%, and median GFR 46.5 ml/min/1.73m2 (range, 21.1-59.5). The starting dose of sunitinib was 50 mg for 22 patients and 37.5 mg for 12 patients. A schedule of sunitinib was 4 weeks on-2 weeks off for 31 patients, 2 weeks on-2 weeks off for 1 patient and daily for 2 patients. Best response was partial response (N=8) or stable disease (N=12). The median OS and PFS was 26.3 (95% CI: 17.1-35.3) and 12.2 (95% CI: 10.2-13.2) months, respectively. Log rank analysis revealed that severity of renal impairment was significantly associated with PFS but not with OS. Most common adverse events (AEs) of non-hematologic toxicities were stomatitis, rash, general edema and fatigue. The most common grade ≥3 AEs were fatigue, neutropenia and thrombocytopenia. Conclusions: Renal insufficiency patients with metastatic RCC did not impact on the efficacy of sunitinib and did not increased toxicities. Clinicians should not hesitate to treat renal insufficiency patients with metastatic renal cell carcinoma.

Toxicities of axitinib, sunitinib and temsirolimus: implications for progression-free and overall survival in metastatic renal cell cancer

2020 ◽  
Author(s):  
Annemarie Uhlig ◽  
Johannes Uhlig ◽  
Lutz Trojan ◽  
Michael Woike ◽  
Marianne Leitsmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Skin Reaction ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Cox Models ◽  
Metastatic Renal Cell Cancer ◽  
Hand Foot Skin Reaction

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand–foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand–foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

An Italian, multicenter, real-world, retrospective study of first-line pazopanib in unselected metastatic renal-cell carcinoma patients: the ‘Pamerit’ study

2020 ◽  
Author(s):  
Alessandra Mosca ◽  
Ugo De Giorgi ◽  
Giuseppe Procopio ◽  
Umberto Basso ◽  
Giacomo Cartenì ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Renal Cell Cancer ◽  
Real World ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Metastatic Renal Cell Cancer ◽  
Metastatic Rcc

Abstract Objective Despite the current immunotherapy era, VEGFR inhibitors maintain effectiveness in metastatic renal cell cancer. Real-world data concerning pazopanib are limited. The aim of this study is to add information about efficacy and safety of pazopanib as first-line treatment in metastatic renal cell cancer patients not enrolled into clinical trials. Methods Retrospective analysis (the PAMERIT study) of first-line pazopanib in real-world metastatic renal cell cancer patients among 39 Centers in Italy. Outcomes were progression-free survival, overall survival, objective response rate and treatment-related adverse events. Kaplan–Meier curves, log-rank test and multivariable Cox’s models were used and adjusted for age, histology, previous renal surgery, International Metastatic RCC Database Consortium score and pazopanib initial dose. Results Among 474 patients, 87.3% had clear cell metastatic renal cell cancer histology. Most of them (84.6%) had upfront renal surgery. Median progression-free survival and overall survival were 15.8 and 34.4 months, respectively, significantly correlating with International Metastatic RCC Database Consortium’s good prognosis (P &lt; 0.001), ECOG PS 0 (P &lt; 0.001), age (&lt;75 years, P = 0.005), surgery (P &lt; 0.001) and response to pazopanib (P &lt; 0.001). After 3 months of pazopanib, overall disease control rate have been observed in 76.6% patients. Among International Metastatic RCC Database Consortium’s favorable group patients, 57/121 (47%) showed complete/partial response. No unexpected AEs emerged. Conclusions In this real-world study, metastatic renal cell cancer patients treated with first-line pazopanib reached greater progression-free survival and overall survival than in pivotal studies and had high response rates when belonging to International Metastatic RCC Database Consortium’s favorable group, without new toxicities. Pazopanib has been confirmed a valid first-line option for International Metastatic RCC Database Consortium’s good prognosis metastatic renal cell cancer patients who cannot be submitted to immunotherapy.

scholarly journals Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review

2006 ◽  
Vol 17 (8) ◽  
pp. 1185-1196 ◽  
Author(s):  
P. Schöffski ◽  
H. Dumez ◽  
P. Clement ◽  
A. Hoeben ◽  
H. Prenen ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Advanced Renal Cell Cancer
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