KIDNEY CANCER - Garvan Institute of Medical Research · renal cell carcinoma. Cancer. 2011 Jul 1;117(13):2873-8. 2. Eggener SE, Yossepowitch 0, Kundu SO, Motzer RJ, Russo P. Risk

KIDNEY CANCER

Dr Anthony Joshua BSc (Med) MBBS PhD FRACP

(with thanks to Dr Danny Heng and OncologyEducation.ca)

Von Hippel Lindau

• 75-80% of sporadic clear cell RCCs have

VHL defect:

– Frameshift / truncation mutation

– Deletion

– Promoter methylation

Cohen et al NEJM 2005

Promoter Von Hippel Lindau Gene

Transcription

CH3

VHL

Von Hippel Lindau

Courtesy sppider.cchmc.org & www.bme.jhu.edu

HIF1a

Ub Ub

Ub Ub

Proteosome Degradation

Of HIF1a

VHL

Von Hippel Lindau HIF1a

Transcription of Genes Associated with Angiogenesis and Proliferation

Angiogenesis and Proliferation

Angiogenesis Cell Proliferation Endothelial Stabilization

VEGF

VEGFR

TGFa/B/

EGFR

PDGF

PDGFR

Cohen et al NEJM 2005

Targeted Therapies: The Revolution

Courtesy AZ

Current and future therapeutic strategies for mRCCs.

Pal S K et al. Mol Cancer Ther 2012;11:526-537 ©2012 by American Association for Cancer Research

Gerlinger M et al. N Engl J Med 2012;366:883-892.

CASE 1

Clinical Scenario

Patient

- 59-year-old male

Presentation

- Hematuria

Medical History

-Diabetes (controlled with medication)

- No surgical history

-No family history of cancer

Personal Habits

- Non-smoker

- No alcohol use

Initial Investigation

Urine Microscopy

- Positive for blood

Cytoscopy

- Normal

Bloodwork

- Serum CBC, Electrolytes, Coagulation Profile, Creatinine all normal

CT Urogram

-Renal tumour with mid renal vein thrombus

-No local invasion, no abdominal metastases

-Normal contralateral kidney

Results: CT Urogram

• Renal tumour with mid renal vein thrombus

• No local invasion

• No abdominal metastases

• Normal contralateral kidney

Continued Investigation

What further diagnostic tests are indicated?

Radiologic: CT chest

Laboratory: Ca2+

Liver function tests

Alkaline phosphatase

Results: CT Chest

• Multiple lung metastases

• Metastases deemed not resectable due to number and location

Decision Point: Patient Prognosis

What prognostic criteria apply to this patient?

International Metastatic Renal Cell Carcinoma Database

(IMDC/Heng) criteria: TKI patients

MSKCC (Motzer) criteria: Immunotherapy patients

What are the IMDC (Heng) criteria?

IMDC Prognostic Factors (Heng Criteria)

Database Consortium Risk Factors

Hemoglobin <normal

Corrected Calcium >normal

Neutrophils >normal

Platelets >normal

Karnofsky Performance Status Grade

<80%

Time from diagnosis to

systemic treatment

<1 year

Heng Criteria & Outcomes (1 point for each)

0 Risk Factors = Favourable

1 or 2 Risk Factors = Intermediate 3 or more Risk Factors = Poor

1. Heng DYC, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: Results from a large, multicenter study. J Clin Oncol. 2009 Dec 1; 27(34): 5794-5799. 2. Heng DYC, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: A population- based study. Lancet Oncol. 2013 Feb; 14(2): 141-148.

Overall Survival By Heng Criteria Score

Heng DYC, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: A population-based study. Lancet Oncol. 2013 Feb; 14(2): 141-148.

Decision Point: Patient Management

How would you manage the patient?

Tumour biopsy and systemic targeted therapy

Cytoreductive nephrectomy and observation

Cytoreductive nephrectomy followed by systemic targeted therapy

Systemic targeted therapy (neoadjuvant) followed by cytoreductive nephrectomy

Enrollment in clinical trial

Cytoreductive Nephrectomy

How Does It Work? Proposed Mechanisms

• Decreased tumour bulk?

• Azotemia and acidosis?

• Decreased immunosuppression? o Bulky tumours may produce products that inhibit

immune system

• Decreased angiogenesis?

Cytoreductive Nephrectomy and Interferon

Flanigan RC, Mickish G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cell cancer: A combined analysis. J Urol. 2004 Mar; 171: 1071-1076.


Change of Preferred Systemic Therapies

• Molecular targeted therapy

o more effective

o better responses in primary tumour

• Trials have yet to report regarding

effectiveness of cytoreductive nephrectomy

(CNx) with targeted therapy


Rationale for CNx

• 90% of trial patients had a nephrectomy

• Palliative benefits: o May reduce hematuria, intractable pain, paraneoplastic symptoms, local

invasion/compression

• Inferred benefit from interferon randomized trial data

• Rare ‘complete response’ with CNx o Regression of metastatic lesions

Rationale for CNx

Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, Bjarnason GA, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Eur Urol. 2014 Oct;66(4):704-10

Benefit of Cytoreductive Nephrectomy Seems to

Depend on Prognosis

Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, Bjarnason GA, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Eur Urol. 2014 Oct;66(4):704-10

Trinh QD, Bianchi M, Hansen J, Tian Z, Abdollah F, Shariat SF, Montorsi F, Perrotte P, Karakiewicz PI, Sun M. In-hospital mortality and failure to rescue after cytoreductive nephrectomy. Eur Urol. 2013 Jun; 63(6):1107-14.

Complications of Cytoreductive Nephrectomy

Complications of Cytoreductive Nephrectomy

Sun M, Abdollah F, Schmitges J, Bianchi M, Tian Z, Shariat SF, Zorn K, et al. Cytoreductive nephrectomy in the elderly: a population-based cohort from the USA. BJU Int. 2012Jun;109(12):1807-12.

Cytoreductive Nephrectomy Trials Best integration of surgery and drug

Trial Rx arms endpoint Planned

biomarkers

EORTC: immed or delayed surgery in mRCC with TKI

OR ->Sutent

vs.

Sutent x 3 -> OR -> sutent

PFS,

OS, QOL, safety

Tissue at baseline and time of surgery

Potential response criteria based on histology and biomarkers.

Subset blood: serum proteins.

CARMENA: French trial

OR -> Sutent

vs.

Sutent alone

( OR at discretion)

OS,

DFS, peri-op morbidity

?

• Patient Factors o Young (<75 years)

1. Fallick ML, McDermott DF, LaRock D, et al. Nephrectomy before interleukin-2 therapy for patients with metastatic renal cell carcinoma. J Urol. 1997; 158:1691-1695.;2. Sun M, Abdollah F, Schmitges J, Bianchi M, Tian Z, Shariat SF, Zorn K, et al. Cytoreductive nephrectomy in the elderly: a population-based cohort from the USA. BJU Int. 2012Jun;109(12):1807-12. 3. Abdollah F, Sun M, Thuret R, Schmitges J, Shariat SF, Perrotte P, et al. Mortality and morbidity after cytoreductive nephrectomy for metastatic renal cell carcinoma: a population-based study. Ann Surg Oncol. 2011Oct;18(10):2988-96. 4.Margulis V, Shariat SF, Rapoport Y, Rink M, Sjoberg DD, Tannir NM, et al. Development of accurate models for individualized prediction of survival after cytoreductive nephrectomy for metastatic renal cell carcinoma. Eur Urol. 2013 May;63(5):947-52 5. Culp SH, Tannir NM, Abel EJ, et al. Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy? Cancer. 2010 Jul 15;116(14):3378-3388. 6. Heng DY, Wells JC, Rini BI, Beuselinck

B, Lee JL, Knox JJ, Bjarnason GA, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Eur Urol. 2014 Oct;66(4):704-10

Patient Selection for Cytoreductive Nephrectomy

• Balance of Benefit and Risk • Prognostic Factors

o Relatively good prognosis

o Patient with ≤ 3 IMDC criteria appear to derive most benefit

• Tumour Factors o Feasible resection (acceptable morbidity)

o Tumour causing morbidity (eg thrombus, pain)

o Clear cell histology (no sarcomatoid)

o Consider biopsy if no histology available

o Tumour bulk (>75% of tumour can be resected with CN)

o No central nervous system or liver metastases

o Consider CT brain

o No unresected symptomatic metastases

Case Resolution

• Patient received cytoreductive nephrectomy followed by systemic therapy (tyrosine kinase inhibitor).

• No major surgery related complications.

Now…...

• Lets imagine he only had 3 lung metastases

Metastasectomy

Expert Opinion • Many cohorts but no RCTs

• n = 3600*

• Location of metastases in studies:

o Lung 60%

o Bone 30%

o Other 25%

• Synchronous metastases: 40%

• Solitary metastases: 36–87%

• Complete metastasectomy: 30%

• Incomplete metastasectomy: 25%

*Leibovich 2005, Naito 2009 1. Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML. Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer. 2011 Jul 1;117(13):2873-8. 2. Eggener SE, Yossepowitch 0, Kundu SO, Motzer RJ, Russo P. Risk score and metastasectomy independently impact prognosis for recurrent renal cell carcinoma. Journal of Urology, 2008 Sep. 180(3): 873.

Metastasectomy

Expert Opinion

• Cohort studies: overall 5-year survival of 15%

• All groups had durable survivors

• Several prognostic factors identified

o Motzer criteria (anemia, hyperCa, PS, >LDH)

o Timing of metastases

o Number of metastases

o Location of metastases

o Completeness of metastasectomy

Breau RH, Blute ML, Surgery for renal cell carcinoma metastasis. Curr Opin Urol, 2010; 20: 375-3781.

Considerations for Metastasectomy

1) Location of Metastases

2) Morbidity of Resection

3) Completeness of Resection

4) Timing


Location of Metastases

• Adrenal

• Pancreas

• Lung

• Bone

• Lymph nodes

• Brain

• Liver

• Multiple locations have worse outcomes – but not necessarily futile

All groups have long-term survivors


Location of Metastases: Lung

• 6 cohorts o Largest cumulate reported experience

• 5-year survival: o Complete resection 40%

o Incomplete or no resection 15%


Resection of Multiple Metastasis

Lung-only metastasis Non-lung-only metastasis

Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML. Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer. 2011 Jul 1;117(13):2873-8.

Morbidity of Resection

• Morbidity of resection must be considered given unknown benefit

• Multidisciplinary surgical team recommended

Completeness of Resection

• Best responses in patients with complete resection

• Incomplete metastasectomy only for palliation

*Leibovich 2005, Naito 2009 1. Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML. Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer. 2011 Jul 1;117(13):2873-8. 2. Eggener SE, Yossepowitch 0, Kundu SO, Motzer RJ, Russo P. Risk score and metastasectomy independently impact prognosis for recurrent renal cell carcinoma. Journal of Urology, 2008 Sep. 180(3): 873.

Timing

• Prognosis: o Best: Late metachronous (>2 years)

o Intermediate: Synchronous (at time of diagnosis)

o Worst: Early metachronous


Metastasectomy Summary

1) Location of Metastases o Lung and glandular organs favourable

2) Consider Morbidity of Resection

3) Complete Resection Important

4) Timing

Patient Follow-up

• Patient offered metastasectomy due to: o Favorable location (lung)

o Acceptable surgical risk

o Complete resection of all METs was feasible

o >2 years between nephrectomy and metastases

Case Conclusion

• Patient underwent complete metastasectomy of all 3 lung nodules

• No major peri-operative complications

• Currently no evidence of disease 2 years post-

metastasectomy

Systemic Therapy Selection Table 1. Treatment recommendations

Setting Patients Therapy (Level 1 evidence) Other options (Less than Level 1 evidence)

Untreated

Good or intermediate risk

Sunitinib Bevacizumab+IFN*

Pazopanib Tivozanib**

HD IL-2 Sorafenib

Observation

Poor risk

Temsirolimus

Sunitinib

Second-line

Cytokine refractory

Prior VEGF targeted

therapy

Prior mTOR

Sorafenib Pazopanib

Tivozanib** Axitinib

Everolimus

Axitinib Nivolumab Cabozatini

b

Sunitinib, bevacizumab+IFN

Targeted therapy not previously used

VEGFr TKI

Third-line*** Any Targeted therapy not previously used

North S, Basappa N, Bjarnason G, Blais N, Canil C, Heng D, et al. Management of advanced kidney cancer: Canadian Kidney Cancer Forum 2013 Consensus Update: Canadian Kidney Cancer Forum 2013. Can Urol Assoc J. 2013 Jul-Aug;7(7-8):238-43.

Pazopanib

• Baseline assessment o Similar to all VEGF targeted therapies

• Toxicities differ compared to Sunitinib o Less fatigue, hand-foot syndrome, diarrhea

o Less concern with mild cytopenias

o More potential issues with hepatotoxicity

• Monitoring on therapy o Similar schedule but need more hepatic monitoring

o ALT, AST, bilirubin that can be life-threatening

o 92.5% of occurred in first 18 weeks of therapy

Neutropenia Grade ≥ 2 (n = 366)

Grade < 2 (n = 404)

P HR

PFS 13.6 7.1 <0.001 0.52

OS 35.6 15.8 <0.001 0.41

Thrombo cytopenia

Grade > 1 (n = 101)

Grade < 1 (n = 669)

PFS 13.7 8.8 0.001 0.65

OS 31.1 21.4 0.014 0.72

HFS Any gr HFS (n = 179)

No HFS (n = 591)

PFS 14.3 8.3 <0.001 0.739

OS 38.2 18.9 <0.001 0.553

Asthenia Fatigue

Any gr A/F (n = 583)

No A/F (n = 187)

PFS 10.9 6.4 <0.001 0.534

OS 26.2 15.0 <0.001 0.634

Improved PFS and OS in pts with Sunitinib related toxicity

Pooled data Data from 770 RCC pts on 5 studies: ESMO/ECCO/ESTRO 2011

This observation was confirmed in 416 patients receiving Sunitinib for GIST.

Median PFS 20.3 weeks

Median PFS 49.4 weeks

Pazopanib: Importance of AUC Median PFS Was More Than Doubled in Subjects with Week 4 C24 > 20.6 µg/mL

Exposure-response of Sunitinib in mRCCC: A PK/PD Approach

PR = partial response; CD = complete response

Houk et al, ASCO 2007, Abstract #5027

Pro

babili

ty o

f a r

espon

se

AUCss sunitinib (μg•hr/mL)

P = 0.023 for AUC

95% CI

Mean

0.0

0.2

0.4

0.6

0.8

1.0

0.5 1.0 1.5 2.0

Longer TTP and OS in mRCC Patients with the Highest Sunitinib Exposure

Houk et al, ASCO 2007, Abstract #5027

Time to tumor progression Overall survival

P=0.014

Relative risk 0.49

P=0.001

Relative risk 0.52

*

Historical

placebo median

*

Historical

placebo median

Days

Fra

cti

on

of

pati

en

ts

no

t p

rog

ress

ed

0 100 200 300 400 500

0.0

0.2

0.4

0.6

0.8

1.0

Days

Fra

cti

on

of

pati

en

ts

su

rviv

ing

0 100 200 300 400 500

0.0

0.2

0.4

0.6

0.8

1.0

600

AUC>Median (N=120)

AUC<Median (N=117)

AUC>Median (N=120)

AUC<Median (N=117)

P=0.014

Relative risk 0.49

P=0.001

Relative risk 0.52

*

Historical

placebo median

*

Historical

placebo median

Days

Fra

cti

on

of

pati

en

ts

no

t p

rog

ress

ed

0 100 200 300 400 500

0.0

0.2

0.4

0.6

0.8

1.0

Days

Fra

cti

on

of

pati

en

ts

su

rviv

ing

0 100 200 300 400 500

0.0

0.2

0.4

0.6

0.8

1.0

600

AUC>Median (N=120)

AUC<Median (N=117)

AUC>Median (N=120)

AUC<Median (N=117)

Axitinib: OS in patients with or without dBP

≥ 90 mmHg – pooled mRCC studies

1.0

0.8

0.6

0.4

0.2

0.0

Su

rviv

al d

istr

ibu

tio

n f

un

ctio

n

Months

0 5 10 15 20 25 30 35 40

dBP < 90 mmHg (n=49) median OS 9.7 months

dBP ≥ 90 mmHg (n=63) median OS 30.1 months

Rini et al. ASCO 2008 See also: Rixe O. et al. Ann Oncol 18:1117-1125, 2007 (Sunitinib)

Patient Follow-up

• Repeat CT after 2 cycles (12 weeks) o Marked radiologic improvement (RECIST)

• Continues on this dose and schedule for 20

months

• Over the last 2 scans, lung nodules slightly larger but asymptomatic

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47.

Patient Follow-up

• Despite slight growth in lung metastases, patient stays on therapy

• Repeat imaging studies after 2 further cycles

o New liver metastases and lung lesions larger

Decision Point: Management

What is your preferred management?

Switch therapy

Stay on current agent

Increase dose of current drug if not on maximal dose

Clinical trial

Outcome of Second-Line Therapy Trials Phase III Data

Treatment PFS (months)

Control PFS (months)

Everolimus vs Placebo 4.0 1.9 (SS)

Axitinib vs Sorafenib 6.7 4.7 (SS)

Temsirolimus vs Sorafenib

4.28 3.91 (NS)

1. Motzer RJ, Escudier B, Oudard S, et al. on behalf of the record-1 Study Group Efficacy of everolimus in advanced renal cell carcinoma: a

double-blind, randomised, placebo-controlled phase iii trial. Lancet. 2008;372:449–56. 2. Rini BI, Escudier B, Tomczak P, et al. Comparative

effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931–

1939. 3. Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, et al. Randomized phase III trial oftemsirolimus versus sorafenib

as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):760-7.

Outcome of Second-Line Therapy Trials IMDC Data

• Response to first line therapy does not predict response to second line therapy

Al-Marrawi MY, Rini BI, Harshman LC, Bjarnason G, Wood L, Vaishampayan U, et al. The association of clinical outcome to first-line VEGF- targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients. Target Oncol. 2013;8:203–209

Patient Follow-up

• Patient changed to Everolimus 10 mg per day

• Baseline assessment prior

o CBC and differential, LFT’s, electrolytes, creatinine, glucose, lipids and triglycerides

o Glucose monitoring, even in non-diabetics

o Lipid monitoring: long term effects of high lipids likely unimportant but acutely elevated triglycerides can cause pancreatitis

o Clinical assessments

Option: mTOR Inhibitors Assessment Schedule

Cycle 1 Cycle 2

CT Scan CT Scan

4 weeks

D1

Full

Assessment

4 weeks

D14

B/W

D14

CBC Optional

Full assessment labs include: CBC and differential, LFT’s, lytes, creatinine, glucose, lipids and triglycerides

D1

Full

Assessment

Monitoring During Second-Line Therapy

• Patients beyond 1st line therapy will need closer follow up:

o More symptoms due to cancer, so may be less

tolerant of side effects

o Increased risk of rapid progression

Patient Follow-up

• Patient tolerates 1st cycle well

• By end of 2nd cycle

o Increasing weight loss, anorexia, right upper quadrant pain, shortness of breath, ECOG 2

o Based on clinical decline, patient and family referred to palliative care

o Repeat imaging: new disease in liver and lungs and left adrenal gland

Case Resolution

• Patient deteriorates quickly over the next two weeks o ECOG = 3

• No further systemic therapy

• Patient dies peacefully at home

Original Article Nivolumab versus Everolimus in Advanced Renal-

Cell Carcinoma

Robert J. Motzer, M.D., Bernard Escudier, M.D., David F. McDermott, M.D., Saby George, M.D., Hans J. Hammers, M.D., Ph.D., Sandhya Srinivas, M.D., Scott S.

Tykodi, M.D., Ph.D., Jeffrey A. Sosman, M.D., Giuseppe Procopio, M.D., Elizabeth R.

Plimack, M.D., Daniel Castellano, M.D., Toni K. Choueiri, M.D., Howard Gurney, M.D., Frede Donskov, M.D., Ph.D., Petri Bono, M.D., Ph.D., John Wagstaff, M.D., Thomas

C. Gauler, M.D., Takeshi Ueda, M.D., Ph.D., Yoshihiko Tomita, M.D., Fabio A. Schutz, M.D., Christian Kollmannsberger, M.D., James Larkin, M.D., Ph.D., Alain

Ravaud, M.D., Ph.D., Jason S. Simon, Ph.D., Li-An Xu, Ph.D., Ian M. Waxman, M.D.,

Padmanee Sharma, M.D., Ph.D., for the CheckMate 025 Investigators

N Engl J Med Volume 373(19):1803-1813

November 5, 2015

Kaplan–Meier Curve for Overall Survival.

Motzer RJ et al. N Engl J Med 2015;373:1803-1813

Overall Survival in Subgroup Analyses and Kaplan–Meier Curve for Progression-free Survival.


Kaplan–Meier Curve for Overall Survival, According to Programmed Death 1 Ligand (PD-L1) Expression Level.


Baseline Demographic and Clinical Characteristics of the Patients Who Underwent Randomization.


Treatment-Related Adverse Events Reported in 10% or More of Treated Patients in Either Group.


Conclusions

• Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus.

Original Article Cabozantinib versus Everolimus in Advanced

Renal-Cell Carcinoma

Toni K. Choueiri, M.D., Bernard Escudier, M.D., Thomas Powles, M.D., Paul N. Mainwaring, M.D., Brian I. Rini, M.D., Frede Donskov, M.D., Ph.D., Hans

Hammers, M.D., Ph.D., Thomas E. Hutson, D.O., Pharm.D., Jae-Lyun Lee, M.D.,

Ph.D., Katriina Peltola, M.D., Ph.D., Bruce J. Roth, M.D., Georg A. Bjarnason, M.D., Lajos Géczi, M.D., Ph.D., Bhumsuk Keam, M.D., Ph.D., Pablo Maroto, M.D., Daniel Y.C. Heng, M.D., M.P.H, Manuela Schmidinger, M.D., Philip W. Kantoff, M.D., Anne

Borgman-Hagey, M.D., Colin Hessel, M.S., Christian Scheffold, M.D., Ph.D., Gisela M. Schwab, M.D., Nizar M. Tannir, M.D., Robert J. Motzer, M.D., for the METEOR

Investigators

N Engl J Med Volume 373(19):1814-1823

November 5, 2015

Kaplan–Meier Estimates of Progression-free Survival.

Choueiri TK et al. N Engl J Med 2015;373:1814-1823

Kaplan–Meier Estimates of Overall Survival.


Baseline Demographic and Clinical Characteristics.


Adverse Events.


Conclusions

• Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.

Documents

KIDNEY CANCER - Garvan Institute of Medical Research · renal cell carcinoma. Cancer. 2011 Jul 1;117(13):2873-8. 2. Eggener SE, Yossepowitch 0, Kundu SO, Motzer RJ, Russo P. Risk