mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi and modified Choi criteria assessed in 2D or 3D to evaluate tumor response

2015 ◽  
Vol 26 (1) ◽  
pp. 278-285 ◽  
Author(s):  
M. Lamuraglia ◽  
S. Raslan ◽  
R. Elaidi ◽  
S. Oudard ◽  
B. Escudier ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mtor Inhibitor ◽  
Tumor Response ◽  
Choi Criteria ◽  
Inhibitor Treatment

Activity of single-agent bevacizumab (B) in patients with metastatic renal cell carcinoma (RCC) previously treated with VEGF- and mTOR-based therapies.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 435-435
Author(s):  
Andrew J. Armstrong ◽  
James D. Turnbull ◽  
Julien Cobert ◽  
Tracy Jaffe ◽  
Michael Roger Harrison ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mtor Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Mtor Inhibition ◽  
Grade 3

435 Background: Given a lack of clinical information on therapeutic efficacy of agents following progression after vascular endothelial growth factor (VEGF) tyrosine kinase inhibition (TKI) and mammalian target of rapamycin (mTOR) inhibition in metastatic renal cell carcinoma (mRCC), we investigated the activity of single agent bevacizumab (B) in this setting. Methods: We conducted a retrospective analysis of single agent B-treated patients with mRCC in the second/third line setting, and identified 21 subjects who met inclusion criteria. The primary endpoint was progression-free survival (PFS). Baseline characteristics, survival, response efficacy outcomes, and toxicities were assessed and summarized. Results: 21 patients (15 women/6 men) were treated with B at a dose of 5 mg/kg/week, dosed q2-3 weeks. Median age was 63, 80% were white, 14% black; 80% had clear cell histology. Median time from diagnosis to B therapy was 3 years (range 1-18); 100% had prior VEGF TKI therapy; 43% had prior mTOR inhibitor; 43% had prior IFN and 19% prior IL-2; median number of prior therapies was 3 (range 1-7); 100% were considered Motzer intermediate risk. Median PFS on B for all subjects was 4.4 mo (95% CI 2.8-9.6) and median OS was 19.4 mo (95% CI 9.9-NR) from start of B therapy. ORR was 2 CR/PR (9.5%), 11 SD (52%), 5 PD, 3 NE. For subjects treated with prior VEGF and mTOR inhibitors, median PFS and OS were 4.4/13.2 mo. Toxicities were as expected and severe adverse events included grade 3-4 fatigue (6), grade 3-4 dehydration (5), and grade 4 failure to thrive (2), grade 4 constipation (2), and grade 3 muscle weakness (2). Conclusions: Single agent B therapy has acceptable toxicity and moderate disease stabilizing activity in selected patients with mRCC who have failed prior VEGF TKI and mTOR inhibitor therapy, and suggests a benefit to continued ongoing VEGF inhibition. Further prospective study of B alone, in combination with mTOR inhibition, or with alternative targeted agents is warranted.

scholarly journals PCN21 PATTERNS OF ANGIOGENESIS INHIBITOR TREATMENT IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA (MRCC) IN IRELAND

2011 ◽  
Vol 14 (3) ◽  
pp. A158
Author(s):  
R. McDermott ◽  
P. Donnellan ◽  
J. McCaffery ◽  
F. Keane ◽  
S.P. Sarda ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Angiogenesis Inhibitor ◽  
Inhibitor Treatment

Everolimus post-progression on tyrosine kinase inhibitors in metastatic renal cell carcinoma: A clinical review of patients demonstrating a durable response and the effective management of treatment toxicity.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 449-449
Author(s):  
James M. Wilson ◽  
Sindhu Ramamurthy ◽  
Ian D. Pedley ◽  
Rhona McMenemin
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mtor Inhibitor ◽  
Progression Free Survival ◽  
Prolonged Treatment ◽  
Free Survival

449 Background: The mammalian target of rapamycin (mTOR) inhibitor everolimus has been licensed as a second line treatment in metastatic renal cell carcinoma (mRCC) following treatment failure with a tyrosine kinase inhibitor (TKI). A randomised placebo control trial of everolimus used in this setting demonstrated only a modest median progression free survival of 4.9 months (Motzer RJ, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010;116:4256-65). Methods: We present 2 patients with a prolonged treatment response - both encountered mTOR inhibitor specific adverse events, the management of which will be discussed. Results: Patient 1: A 47 year old man with mRCC, previously treated with the Atzpodien regimen followed by sunitinib. A radiological response was seen after 2 treatment cycles of Everolimus and has remained stable for 25 months to date. A triglyceride level of 32.2 mmol/l has responded to a 50% dose reduction, dietary advice and the addition of a fibrate without loss of disease control. Patient 2: A 62 year old man with mRCC initially treated with Interferon followed by sunitinib. He developed radiological evidence of pneumonitis after 2 months of everolimus but did not experience (G3) symptoms until 2 months later. Pneumonitis responded to treatment deferral and corticosteroids and did not recur when everolimus was reintroduced. He achieved 18 months of PFS. Conclusions: Everolimus can initiate prolonged periods of progression free survival when used after progression on a TKI. The treatment is well tolerated and adverse events can be easily managed to allow ongoing therapy. Our further investigation, including tumor gene profiling, of such patients will allow a more personalised approach in the management of mRCC and improved prognostication in the clinic.

scholarly journals Dynamic Changes in Plasma Osteopontin as a Markers of Tumor Response in Metastatic Renal Cell Carcinoma (RCC) Patients Treated with Pazopanib

2012 ◽  
Vol 23 ◽  
pp. ix275-ix276
Author(s):  
H.T. Tran ◽  
Y. Liu ◽  
Y. Lin ◽  
A.J. Zurita Saavedra, ◽  
K.L. Baker-Neblett ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Response ◽  
Dynamic Changes

Rechallenge with mTOR Inhibitors in Metastatic Renal Cell Carcinoma Patients Who Progressed on Previous mTOR Inhibitor Therapy

Oncology ◽  
2013 ◽  
Vol 85 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Agnes Maj-Hes ◽  
Jacques Medioni ◽  
Florian Scotte ◽  
Manuela Schmidinger ◽  
Gero Kramer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mtor Inhibitor ◽  
Mtor Inhibitors ◽  
Inhibitor Therapy

Phase III trial of dovitinib (TKI258) versus sorafenib in patients with metastatic renal cell carcinoma after failure of anti-angiogenic (VEGF-targeted and mTOR inhibitor) therapies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4683-TPS4683 ◽  
Author(s):  
Robert John Motzer ◽  
Camillo Porta ◽  
Georg A. Bjarnason ◽  
Cezary Szcylik ◽  
Sun Young Rha ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Growth Factor ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mtor Inhibitor ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Patient Reported

TPS4683 Background: Standard first- and second-line treatments in metastatic renal cell carcinoma (mRCC) target the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) signaling pathways. However, signaling through other pathways, including the fibroblast growth factor receptor (FGFR) pathway, may account for tumor resistance to these standard therapies. Dovitinib (TKI258) is an oral FGF, VEGF, and platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitor, with IC50 values of ≈ 10 nM. In a phase II study of 59 RCC patients, many of whom had failed prior VEGF-targeted and mTOR inhibitor therapies, dovitinib (500 mg/day on a 5-days-on/2-days-off schedule) was well tolerated and demonstrated promising anti-tumor effects, with progression-free survival (PFS) of 5.5 months (Angevin et al, ASCO 2011). Methods: Approximately 550 patients from over 26 countries will be randomized 1:1 in this multicenter, open-label, randomized phase III trial (NCT01223027) to receive dovitinib (500 mg/day on a 5-days-on/2-days-off schedule) or sorafenib (400 mg twice daily). Eligible mRCC patients must have failed 1 VEGF-targeted therapy and 1 mTOR inhibitor (disease progression on or within 6 months of stopping the prior treatment). Patients will remain on study until disease progression, unacceptable toxicity, death, or discontinuation for any other reason. No treatment crossover is planned. The primary endpoint is PFS as determined by central radiology assessment according to RECIST v1.1, with evaluations performed every 8 weeks. Secondary endpoints include overall survival, overall response rate, safety, patient-reported outcomes, and pharmacokinetics. The pharmacodynamic effects of dovitinib on plasma/serum biomarkers will also be explored. The data monitoring committee last reviewed the trial on 20 December 2011 and recommended that the trial continue as planned. This is the first third-line randomized clinical trial in mRCC to evaluate a multitargeted inhibitor of FGFR.

Sign in / Sign up

Export Citation Format

Share Document