1. Clinical case HIGHLIGTHS IN ADVANCED RENAL CELL CARCINOMA MANAGEMENT Roma, 24 febbraio 2012 Cristina Masini Azienda Ospedaliero Universitaria Policlinico di Modena

2. 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

3. What would you do now? 1. Lumbar CT scan 1. Lumbar MRI 2. Bone scan 3. All of the above

4. CT scan Osteolytic lesion of L2 1

5. STIR sequence 2 Non-enhanced T1 Lumbar MRI Osteolysis of L1-L2 Newly formed tissue that compresses the dural sac

6. CT staging with contrast Chest and abdomen CT: Mass in left kidney (9 x 7 cm) Multiple lymph adenopathies Bone scan L2 lesion

7. What would you do now? Goal: quality of life 1.Bone biopsy  Radiotherapy 2.Bone biopsy and vertebroplasty 3.Embolization  spinal decompression and stabilization 4.Kidney biopsy  systemic therapy 5.Best supportive care

8. July 2008 Embolization of spinal pathological vascular bed (L1-L2) Decompressive laminectomy and stabilization Histology of L2 lesion: clear cell carcinoma Radiotherapy D11-L4

9. What would you do now? 1.Systemic therapy 2.Left nephrectomy 3.Left nephrectomy  systemic therapy 4.Best supportive care 5.Other

10. Motzer score: intermediate risk August 2008 Clear cell carcinoma Fuhrman nuclear grading system: G2 pT2a, Nx Left nephrectomy

11. 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

12. 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

13. 1) Hypertension 170/100 mm Hg (G2) Good control of blood pressure: 140/80 mm Hg 2) HFSR G2  Start Ramipril 10 mg daily  Continue Sunitinib 50 mg daily (4/2) January 2009...after 3 months of Sunitinib

14. Ecocardiography: EF 45% (G2) Asymptomatic patient Normal ECG Chest rx: negative  Start Potassium Canrenoate 100 mg daily, bisoprolol 1.25 mg daily  Reduced dose of Sunitinib: 37.5 mg daily (4/2) April 2009...after 6 months of Sunitinib

15. 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

16.  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

17. 1.Sorafenib 2.Continue Sunitinib 3.Everolimus 4.Best supportive care What would you do now?

18. Which is the optimal sequential treatment? No responseIntolerance Short term benefit Long term benefit Porta C, et al. EJMCO 2010 Eisen T, modified TKIs

19. Stenner F, et al. Oncology (submitted). Sequencing TKIs: no cross-resistance

20. 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 angiogenesis 2 The issues of long responders….

21. 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

22. 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

23. 1.Rechallenge Sunitinib 2.Everolimus 3.Best supportive care 4.Pazopanib What would you do now?

24. HR n p EVE PLAC Everolimus was as effective after 2 Tkis as it was after 1 TKi Hazard Ratio Motzer RJ, Cancer 2010 Hutson TE, EJC 2009, abs Median PFS, mos

25. September 2011  Start Everolimus 10 mg daily  Continue Zoledronic acid 4 mg every 3 months January 2012...after 4 months of Everolimus Chest and abdomen CT: Reduction of pleural effusion, unchanged liver and adrenal masses SD  ongoing Everolimus