Clinical case

HIGHLIGTHS IN ADVANCED RENAL CELL CARCINOMA MANAGEMENTRoma, 24 febbraio 2012

Cristina MasiniAzienda Ospedaliero Universitaria Policlinico di Modena

E.M., ♂, 73 years old

June 2008

• Lumbar pain, not responsive to common anti -inflammatory drugs

• Absence of other symptoms

• Spinal RX: fracture of L2, invisible right pedicle

What would you do now?

1. Lumbar CT scan 1. Lumbar MRI2. Bone scan3. All of the above

CT scanOsteolytic lesion of L2

1

STIR sequence

2

Non-enhanced T1

Lumbar MRI

Osteolysis of L1-L2Newly formed tissue that compresses the dural sac

CT staging with contrast

Chest and abdomen CT:

• Mass in left kidney (9 x 7 cm)

• Multiple lymph adenopathies

Bone scan

L2 lesion

What would you do now?Goal: quality of life

1. Bone biopsy Radiotherapy2. Bone biopsy and vertebroplasty3. Embolization spinal decompression and

stabilization4. Kidney biopsy systemic therapy5. Best supportive care

July 2008Embolization of spinal

pathological vascular bed (L1-L2)

Decompressive laminectomy and stabilization

Histology of L2 lesion: clear cell carcinoma

Radiotherapy D11-L4

What would you do now?

1. Systemic therapy2. Left nephrectomy3. Left nephrectomy systemic therapy4. Best supportive care5. Other

Motzer score: intermediate risk

August 2008

Clear cell carcinoma

Fuhrman nuclear grading system: G2

pT2a, Nx

Left nephrectomy

Retrospective analysis 60 pts with solitary bone metastasis:33 pts had surgical treatment (13 wide resection, 20 local stabilization)27 pts had no surgical treatment

33 pts with bone lesion of axial skeleton 27 pts with bone lesion of appendicular skeleton

Fuchs B., Clin Orthop & related Res 2005

Solitary Bone Metastasis from Renal Cell Carcinoma

October 2008

Start Sunitinib 50 mg daily for 4/2 weeks Zoledronic acid 4 mg every 4 weeks

Lumbar CT:

Spinal stabilization

L1-L2 extensive osteolysis

Chest and abdomen CT:

appearance of bilateral lung lesions

1) Hypertension 170/100 mm Hg (G2)

Good control of blood pressure: 140/80 mm Hg

2) HFSR G2

Start Ramipril 10 mg dailyStart Ramipril 10 mg daily Continue Sunitinib 50 mg daily (4/2)Continue Sunitinib 50 mg daily (4/2)

January 2009...after 3 months of Sunitinib

Ecocardiography: EF 45% (G2)

Asymptomatic patient

Normal ECG

Chest rx: negative

Start Potassium Canrenoate 100 mg daily, bisoprolol 1.25 mg dailyStart Potassium Canrenoate 100 mg daily, bisoprolol 1.25 mg dailyReduced dose of Sunitinib: 37.5 mg daily (4/2)Reduced dose of Sunitinib: 37.5 mg daily (4/2)

April 2009...after 6 months of Sunitinib

May 2009……..after 1 month

Asymptomatic patient

Ecocardiography: EF 55%

Sunitinib 37.5 mg daily (4/2)Bisoprolol 2.5 mg daily and potassium canrenoate 100 mg daily

Chest and abdomen CT:Right pleural effusion and appearance of adrenal mass (3 cm)

Pleural fluid citology: neoplastic cells

Ecocardiography: EF 55%

October 2010...after 24 months of Sunitinib

Progression disease

1. Sorafenib2. Continue Sunitinib3. Everolimus4. Best supportive care

What would you do now?

Which is the optimal sequential treatment?

No response Intolerance Short term benefit

Long term benefit

Porta C, et al. EJMCO 2010Eisen T, modified

TKIs

Stenner F, et al. Oncology (submitted).

Sequencing TKIs: no cross-resistance

1. Eladi R, et al. (manuscript in preparation); 2. Porta C, et al. BJU Int 2011 (Editorial in press)

This is probably due by the fact that in RCC is so heavily dependant on angiogenesis, inhibiting mTOR ultimately results in a continuous, even though indirect, inhibition of angiogenesis2

The issues of long responders….

November 2010

Start Sorafenib 800 mg daily Continue Zoledronic acid 4 mg every 3 months

January 2011...after 2 months of Sorafenib

HFSR (G2)

Stop Sorafenib for 7 days HFSR G1 Restart Sorafenib 800 mg daily

Chest and abdomen CT:Increase of pleural effusion, adrenal mass (4 cm), appearance of liver lesion

August 2011...after 9 months of Sorafenib

Progression disease: STOP SORAFENIB

1. Rechallenge Sunitinib2. Everolimus3. Best supportive care4. Pazopanib

What would you do now?

HR n p EVE PLAC

Everolimus was as effective after 2 Tkis as it was after 1 TKi

Hazard Ratio

Motzer RJ, Cancer 2010Hutson TE, EJC 2009, abs

Median PFS, mos

September 2011

Start Everolimus 10 mg daily Continue Zoledronic acid 4 mg every 3 months

January 2012...after 4 months of Everolimus

Page: 23 of 177Page: 23 of 177 I M: 23 SE: 2I M: 23 SE: 2Compressed 8: 1Compressed 8: 1

cm cm

Chest and abdomen CT:Reduction of pleural effusion, unchanged liver and adrenal masses

SD ongoing Everolimus