La presentazione è in caricamento. Aspetta per favore

La presentazione è in caricamento. Aspetta per favore

Scuola di uro Oncologia G. Cartenì Direttore U.O.S.C. di Oncologia Medica A.O.R.N. A. Cardarelli Napoli Roma, 12/13 Luglio 2013 CONTROVERSIE ONCOLOGICHE.

Presentazioni simili


Presentazione sul tema: "Scuola di uro Oncologia G. Cartenì Direttore U.O.S.C. di Oncologia Medica A.O.R.N. A. Cardarelli Napoli Roma, 12/13 Luglio 2013 CONTROVERSIE ONCOLOGICHE."— Transcript della presentazione:

1

2 Scuola di uro Oncologia G. Cartenì Direttore U.O.S.C. di Oncologia Medica A.O.R.N. A. Cardarelli Napoli Roma, 12/13 Luglio 2013 CONTROVERSIE ONCOLOGICHE L’oncologo risponde all’urologo: PRIMA LINEA DI TRATTAMENTO

3  Quali criteri vengono utilizzati per scegliere il farmaco da utilizzare in prima linea ?  Come monitorizzare la terapia ? Criteri di successo/insuccesso  La gestione delle complicanze/effetti collaterali  Trattamento delle metastasi ossee  Associazione di farmaci ? terapie sequenziali ?

4 How to choose first line treatment Prognostic profile (Motzer/Heng) Toxicity profile and comorbidities Disease characteristics (site/sympthoms) Sequential strategies Oral/iv administration Physician experience Patient preference Biomarkers in development…!

5

6 Linee Guida EAU 2010

7 Risk statusRecommendationLevel of evidence Favourable or intermediate Sunitinib Bevacizumab + IFN-α Pazopanib I, A II, A Poor riskTemsirolimusII, A First-line treatment guidelines for clear cell mRCC: ESMO 2012 Escudier B, et al. Ann Oncol 2012;23(Suppl 7):vii65–71

8

9

10

11

12

13

14

15

16 How to choose first line treatment Prognostic profile (Motzer/Heng) Toxicity profile and comorbidities Disease characteristics (site/sympthoms) Sequential strategies Oral/iv administration Physician experience Patient preference Biomarkers in development…!

17 Randomized, Open Label, Phase III Trial of Pazopanib versus Sunitinib in First-line Treatment of Patients with Metastatic Renal Cell Carcinoma (mRCC): Results of the COMPARZ Trial Robert Motzer 1, T. E. Hutson 2, James Reeves 3, Robert Hawkins 4, Jun Guo 5, Paul Nathan 6, Michael Staehler 7, Paul de Souza 8, Jaime R. Merchan 9, Kate Fife 10, Jie Jin 11, Robert Jones 12, Hirotsugu Uemura 13, Ugo De Giorgi 14, Ulrika Harmenberg 15, Jinwan Wang 16, David Cella 17, Lauren McCann 18, Keith Deen 18, and Toni K. Choueiri 19 1 Memorial Sloan Kettering Cancer Center, NY, NY, USA; 2 Baylor Sammons Cancer Center/Texas Oncology, Dallas, TX, USA; 3 Florida Cancer Specialists, Fort Myers, FL, USA; 4 University of Manchester and The Christie Hospital, NHS Foundation Trust, Manchester, United Kingdom; 5 Renal Cancer and Melanoma Unit, Peking University Cancer Hospital, Beijing, China; 6 Mount Vernon Hospital, Middlesex, United Kingdom; 7 Department of Urology, Interdisciplinary Centre on Renal Tumors, University of Munich, Munich, Germany; 8 University of Western Sydney School of Medicine, MMRG, CRG, Sydney, Australia; 9 University of Miami, Sylvester Cancer Center, Miami, FL, USA: 10 Oncology Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; 11 Peking University First Hospital, Beijing, China; 12 Institute of Cancer Sciences University of Glasgow, Glasgow, United Kingdom; 13 Department of Urology, Kinki University Faculty of Medicine, Osaka, Japan; 14 IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy; 15 Department of Oncology, Radiumhemmet Karolinska University Hospital, Stockholm, Sweden; 16 Cancer Hospital, CAMS & PUMC, Beijing, China; 17 Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA ; 18 GlaxoSmithKline, Inc., Collegeville, PA, USA; 10 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

18 PFS (ITT population)Pazopanib (n=557)Sunitinib (n=553) Median PFS, months (95% CI)8.4 (8.3, 10.9)9.5 (8.3, 11.1) HR (95% CI) (0.8982, ) PFS (PP population)Pazopanib (n=501)Sunitinib (n=494) Median PFS, months (95% CI)8.4 (8.3, 10.9)10.2 (8.3, 11.1) HR (95% CI)1.069 (0.910, 1.255) PP, per-protocol 1. GSK. Clinical Study Register. Study Available at: (last accessed February 2013); 2. Motzer RJ, et al. Presented at ESMO 2012; Abstract LBA8; 3. Available at (last accessed April 2013) COMPARZ: PFS (IRC-assessed) Non-inferiority met if upper bound of 95% CI for HR <1.25 (EMA requested ≤ )

19 PFS (ITT population)Pazopanib (n=557)Sunitinib (n=553) Median PFS, months (95% CI)8.4 (8.3, 10.9)9.5 (8.3, 11.1) HR (95% CI) (0.8982, ) PFS (PP population)Pazopanib (n=501)Sunitinib (n=494) Median PFS, months (95% CI)8.4 (8.3, 10.9)10.2 (8.3, 11.1) HR (95% CI)1.069 (0.910, 1.255) PP, per-protocol 1. GSK. Clinical Study Register. Study Available at: (last accessed February 2013); 2. Motzer RJ, et al. Presented at ESMO 2012; Abstract LBA8; 3. Available at (last accessed April 2013) COMPARZ: PFS (IRC-assessed) Non-inferiority met if upper bound of 95% CI for HR <1.25 (EMA requested ≤ )

20 PFS (ITT population)Pazopanib (n=557)Sunitinib (n=553) Median PFS, months (95% CI)8.4 (8.3, 10.9)9.5 (8.3, 11.1) HR (95% CI) (0.8982, ) PFS (PP population)Pazopanib (n=501)Sunitinib (n=494) Median PFS, months (95% CI)8.4 (8.3, 10.9)10.2 (8.3, 11.1) HR (95% CI)1.069 (0.910, 1.255) PP, per-protocol 1. GSK. Clinical Study Register. Study Available at: (last accessed February 2013); 2. Motzer RJ, et al. Presented at ESMO 2012; Abstract LBA8; 3. Available at (last accessed April 2013) COMPARZ: PFS (IRC-assessed) Non-inferiority met if upper bound of 95% CI for HR <1.25 (EMA requested ≤ )

21 COMPARZ study design: Phase III, open-label, non- inferiority trial Pazopanib 800 mg QD Continuous daily dosing Enrolment criteria: Locally advanced or mRCC Clear-cell histology No prior systemic therapy Measurable disease (RECIST 1.0) KPS ≥70 Adequate organ function N=927 Sunitinib 50 mg QD Schedule 4/2 Randomised 1:1 KPS, Karnofsky Performance Scale; RECIST, Response Evaluation Criteria in Solid Tumors; Schedule 4/2, 4 weeks on treatment, 2 weeks off (NCT ; NCT ) Study start: August 2008 VEG Phase III n=927 VEG Phase II (Asia) n=183 COMPARZ: 1,110 patients N=1,110

22 Primary Endpoint: Progression-free Survival (independent review) Pazopanib Sunitinib NMedian PFS (95% CI) Pazopanib mo (8.3, 10.9) Sunitinib mo (8.3, 11.1) HR (95% CI ) = (0.898,1.220)

23 Interim Analysis of Overall Survival Pazopanib Sunitinib NMedian OS (95% CI) Pazopanib mos (26.2, 35.6) Sunitinib mos (25.3, 32.5) HR (95% CI ) = (0.762,1.082) P-value = 0.275

24 COMPARZ: Timing of assessments Mean change from baseline Time Sunitinib Pazopanib Disease assessments QoL assessments QoL, quality of life Motzer RJ, et al. Presented at ESMO 2012; Abstract LBA8 Cella D, et al. Presented at ASCO-GU 2012; Abstract 346 Week 4 Week 6 Week 4

25 Most Common Adverse Events (treatment-emergent) Adverse Event a Pazopanib (n = 554) %Sunitinib (n = 548) % All GrsGr 3/4All GrsGr 3/4 Any event b >9959/15>9957/17 Diarrhea 63 9/0 57 7/<1 Fatigue 55 10/< /<1 Hypertension 46 15/< /<1 Nausea 45 2/0 46 2/0 Decreased appetite 37 1/0 37 3/0 ALT increased 31 10/2 18 2/<1 Hair color changes 30 0/0 10 <1/0 Hand-foot syndrome 29 6/ /<1 Taste Alteration 26 <1/0 36 0/0 Thrombocytopenia 10 2/< /4 a AE ≥30% in either arm b 2% of patients in pazopanib arm and 3% of patients in sunitinib arm had grade 5 adverse events.

26 COMPARZ: Common AEs (treatment-emergent) AE* Pazopanib (n=554), %Sunitinib (n=548), %Risk ratio95% CI All grades Grade 3/4 All grades Grade 3/4All grades Any event † >9959/15>9957/17NA Diarrhoea639/0577/< , 1.20 Fatigue5510/<16317/< , 0.96 Hypertension46 15/<14115/< , 1.31 Nausea452/0462/ , 1.11 Decreased appetite371/0373/0NA ALT increased3110/2182/< , 2.17 Hair colour changes300/010<1/0NA HFS296/05011/< , 0.68 Taste alteration26<1/0360/0NA Thrombocytopenia102/<13412/ , 0.40 *AE ≥30% in either arm; † 2% of patients in pazopanib arm and 3% of patients in sunitinib arm had grade 5 AEs ALT, alanine transaminase; AST, aspartate transaminase; HFS, hand–foot syndrome; NA, not applicable

27 Treatment Duration and Dose Adjustments Pazopanib (n = 554) Sunitinib (n = 548) Median duration of treatment (months, range) 8.0 (0−40)7.6 (0−38) Dose reductions, %4451 Discontinuations due to AEs 1, % Most common reason: pazopanib arm (liver event, 6%); sunitinib arm (cytopenia, 3%)

28 InstrumentDomain Description Treatment difference : mean change from baseline 2 P -value FACIT-F Fatigue/Total score 2.32<0.001 FKSI-19 Kidney Symptom Index/Total score Physical Emotional Treatment Side Effects Functional Well Being Cancer Treatment Satisfaction Questionnaire (CTSQ) Expectations of Therapy Feelings about Side Effects 8.50<0.001 Satisfaction with Therapy 3.21<0.001 Supplementary Quality of Life Questionnaire (SQLQ) Worst mouth/throat soreness 0.505< Worst foot soreness Worst hand soreness Limitations due to mouth/throat soreness 0.94<0.001 Limitations due to foot soreness Quality of Life Results (first 6 months 1 ) 1 Pre-specified analysis. HRQoL changes in mean scores over time were analyzed with a repeated measures analysis of covariance (ANCOVA). 2 Yellow Font: favors pazopanib. Blue Font: favors sunitinib. P-value <0.05 is statistically significant

29 InstrumentDomain Description Treatment difference : mean change from baseline 2 P -value FACIT-F Fatigue/Total score 2.32<0.001 FKSI-19 Kidney Symptom Index/Total score Physical Emotional Treatment Side Effects Functional Well Being Cancer Treatment Satisfaction Questionnaire (CTSQ) Expectations of Therapy Feelings about Side Effects 8.50<0.001 Satisfaction with Therapy 3.21<0.001 Supplementary Quality of Life Questionnaire (SQLQ) Worst mouth/throat soreness 0.505< Worst foot soreness Worst hand soreness Limitations due to mouth/throat soreness 0.94<0.001 Limitations due to foot soreness Quality of Life Results (first 6 months 1 ) 1 Pre-specified analysis. HRQoL changes in mean scores over time were analyzed with a repeated measures analysis of covariance (ANCOVA). 2 Yellow Font: favors pazopanib. Blue Font: favors sunitinib. P-value <0.05 is statistically significant

30 Quality of Life Results: PISCES 1 Randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma InstrumentTimingDomain Description Treatment difference 2,3 P value FACIT- F Every 2 weeks Fatigue/Total score Supplementary Quality of Life Questionnaire Every 2 weeks Worst mouth/throat soreness0.38<0.001 Worst foot soreness Worst hand soreness Limitations due to mouth/throat soreness0.60<0.001 Limitations due to foot soreness Escudier BJ, et al.. J Clin Oncol 30, 2012 (suppl; abstr CRA4502) 2.Cella D, et al. ESMO Congress 2012 poster 792PD 3.Yellow Font: favors pazopanib P-value <0.05 is statistically significant

31

32 How to choose first line treatment Prognostic profile (Motzer/Heng) Toxicity profile and comorbidities Disease characteristics (site/sympthoms) Sequential strategies Oral/iv administration Physician experience Patient preference Biomarkers in development…!

33 How to choose first line treatment Prognostic profile (Motzer/Heng) Toxicity profile and comorbidities Disease characteristics (site/sympthoms) Sequential strategies Oral/iv administration Physician experience Patient preference Biomarkers in development…!

34 How to choose first line treatment Prognostic profile (Motzer/Heng) Toxicity profile and comorbidities Disease characteristics (site/sympthoms) Sequential strategies Oral/iv administration Physician experience Patient preference Biomarkers in development…!

35 How to choose first line treatment Prognostic profile (Motzer/Heng) Toxicity profile and comorbidities Disease characteristics (site/sympthoms) Sequential strategies Oral/iv administration Physician experience Patient preference Biomarkers in development…!

36 How to choose first line treatment Prognostic profile (Motzer/Heng) Toxicity profile and comorbidities Disease characteristics (site/sympthoms) Sequential strategies Oral/iv administration Physician experience Patient preference Biomarkers in development…!

37

38 Significantly more patients preferred pazopanib over sunitinib (primary endpoint) 1 Patients (%) p< % (n=80) 22% (n=25) 8% (n=9) 1.Escudier B, et al. J Clin Oncol 2012;30 suppl: abstr CRA4502.

39

40  Quali criteri vengono utilizzati per scegliere il farmaco da utilizzare in prima linea ?  Come monitorizzare la terapia ? Criteri di successo/insuccesso  La gestione delle complicanze/effetti collaterali  Trattamento delle metastasi ossee  Associazione di farmaci ? terapie sequenziali ?

41  Necessario fare riferimento a criteri: –Diagnostica strumentale –Clinici –Laboratorio Valutazione dello stato di malattia in corso di trattamento con targeted therapies

42 Criteri di risposta (RECIST) - Criticità La risposta parziale è definita come tumor shrinkage pari al 30%  Un tumor shrinkage del < 30% è un risultato positivo per il paziente. Il controllo del tumore potrebbe essere un endpoint clinicamente più rilevante 2  Potrebbe non essere appropriato per valutare la risposta alle targeted therapies (differente meccanismo d’azione)  Le targeted therapies possono determinare necrosi tumorale piuttosto che tumor shrinkage 3 1. Therasse P, et al. J Natl Cancer Inst 2000; 92:205–16 2. Nygren P, et al Acta Oncologia 2008; 47:316–29 3. Abou-Alfa G, et al. J Clin Oncol 2006;24:4293–300 I criteri RECIST rappresentano lo standard di valutazione di risposta al trattamento in studi clinici su farmaci antitumorali 1 Si basa sulle risposte agli agenti antitumorali citotossici Non si misurano le necrosi tumorali

43 Revisione criteri di risposta (RECIST v. 1.1) Principali modifiche proposte: -Numero delle lesioni valutabili; -Dimensioni dei linfonodi patologici; -Conferma della risposta; -Supporto FDG-PET per valutare le progressioni.

44 Come valutare la risposta al trattamento nell’era delle targeted therapies? I criteri RECIST e la loro più recente revisione non tengono conto di: Tecniche di imaging funzionale come la PET o la RMN Valutazione anatomica volumetrica del tumore Necessità di nuove metodiche di immagine atte a studiare la vascolarizzazione e la necrosi tumorale FDG-PET DCE-US DCE-MRI

45 Imaging funzionale con DCE-US Valutazione della risposta a sorafenib Abdominal lymph node from an RCC in a 37 year-old woman (good responder) treated with sorafenib Lamuraglia et al.EJC 2006 DCE-US before treatment shows contrast uptake throughout the tumour estimated at 81% DCE-US after 3 weeks of treatment shows contrast uptake throughout the tumour estimated at 48% DCE-US after 6 weeks of treatment shows contrast uptake throughout the tumour estimated at 31%

46

47 sensitivityspecificity MASS criteria 86%100% SACT criteria 75%100% Smith AD, Shah SN, Rini BI, Lieber ML, Remer EM. Morphology, Attenuation, Size, and Structure (MASS) criteria: assessing response and predicting clinical outcome in metastatic renal cell carcinoma on antiangiogenic targeted therapy. AJR Am J Roentgenol Jun;194(6): CONCLUSION: Assessment of metastatic RCC target lesions on CECT for changes in morphology, attenuation, size, and structure by MASS Criteria is more accurate than response assessment by SACT Criteria, RECIST, or modified Choi Criteria. Furthermore, the use of MASS Criteria for imaging response assessment showed high interobserver agreement and may predict disease outcome in patients with metastatic RCC on targeted therapy identifying patients with progression-free survival of >250 days

48  Necessario fare riferimento a criteri: –Diagnostica strumentale –Clinici –Laboratorio Valutazione dello stato di malattia in corso di trattamento con targeted therapies

49 Criteri clinici  Esame obiettivo  Performance status  Sintomi tumore-correlati  Perdita di peso  Consumo di analgesici  Qualità di vita del paziente

50 Criteri di laboratorio  Emocromo completo  Funzionalità epatica  Funzionalità renale  LDH  Calcemia Tossicità o progressione di malattia?

51 Quando finisce una prima linea di trattamento ?

52 In assenza di una sicura progressione obiettiva, i criteri clinici che depongono per un beneficio per il paziente, devono sempre orientare verso la prosecuzione del trattamento con l’agente target in corso E viceversa ….

53 Sintomi all’esordio – Ematuria – Anemia – Dolori addominali – Calo ponderale – Astenia – Dispnea – Il paziente viene trasportato a braccia alla visita

54 Emoglobina: 9.0 gr/dl LDH 920 PS: sec Karnofsky 70% Pluri-metastatico

55

56 Maggio 2010 – Praticati due cicli di Sutent – Netto miglioramento delle condizioni cliniche – Molto ridotto il dolore addominale – Astenia quasi assente – Hgb 11 g/dl – Calcemia 8.6 mg/dl – LDH 650 – Karnofsky 80%

57

58

59

60

61

62  Quali criteri vengono utilizzati per scegliere il farmaco da utilizzare in prima linea ?  Come monitorizzare la terapia ? Criteri di successo/insuccesso  La gestione delle complicanze/effetti collaterali  Trattamento delle metastasi ossee  Associazione di farmaci ? terapie sequenziali ?

63 ccRCC Predictive markers of target therapy Bio-Clinical – Hypertension (>90 mm/hg DBP) – LDH – Hypothiroidism (increased TSH)

64 Hypertension Biomarker of Efficacy with Sunitinib B Rini, J Natl Cancer Inst 2011; 103:

65 OS with landmark at 8 weeks. B Rini, Clin Cancer Res; 17(11); 3841– Diastolic blood pressure Biomarker of efficacy with axitinib in solid tumors

66 Serum LDH Biomarker with Temsirolimus Andrew J Armstrong et al, J Clin Oncol 30:

67 Objective Remission According to Response Evaluation Criteria in Solid Tumors Based on Increased Thyroid-Stimulating Hormone Levels Hypothyroidism (increased TSH) Biomarker of activity with TKI in solid tumors Schmidinger M, Cancer 2011

68 Implicazioni cliniche Trattiamo FINO alla tossicità ? Trattiamo LA tossicità ? Ruolo dei farmaci per la tossicità ?

69 Take home messages Metodi di valutazione e misure profilattiche verso gli effetti collaterali possono confondere questi risultati Gran parte dei risultati derivano da studi retrospettivi (validazione in studi prospettici) I ‘potenziali benefici’ derivanti dalla somministrazione contemporanea di medicinali devono essere considerati Nessuno di questi marcatori  ideale: il marcatore ideale predittivo  valutabile prima del trattamento, piuttosto che durante il trattamento

70  Quali criteri vengono utilizzati per scegliere il farmaco da utilizzare in prima linea ?  Come monitorizzare la terapia ? Criteri di successo/insuccesso  La gestione delle complicanze/effetti collaterali  Trattamento delle metastasi ossee  Associazione di farmaci ? terapie sequenziali ?

71 Key Factors for Successful Therapy Management in mRCC Dosing Treatment Duration Optimum Efficacy Side-effect Management Schedule

72  Quali criteri vengono utilizzati per scegliere il farmaco da utilizzare in prima linea ?  Come monitorizzare la terapia ? Criteri di successo/insuccesso  La gestione delle complicanze/effetti collaterali  Trattamento delle metastasi ossee  Associazione di farmaci ? terapie sequenziali ?

73 Rosen et al. Cancer 2004; 100: Zoledronic acid significantly extended (A) the time to first skeletal complication compared with placebo and (B) the time to first pathologic fracture compared with placebo

74 Rosen et al. Cancer 2004; 100: mRCC patients: 74 total reduction of skeletal complications: 74% (ZA) vs 37% (placebo) (p=0.015) absolute reduction: 37% time to First On-Study SRE: 424 days vs 72 days (p=0.007)

75 Three Identical International, Randomized, Double-Blind, Active-Controlled Trials Lipton A, Fizazi K, Stopeck A, et al. Eur J Cancer 2012 Key Inclusion Criteria Adults with breast, prostate, other solid tumors, or multiple myeloma and ≥1 bone metastasis Key Exclusion Criteria current or prior IV bisphosphonate administration creatinine clearance <30 mL/min Recommended: Daily supplementation with calcium (≥500 mg) and vitamin D (≥400 U) RANDOMIZATIONRANDOMIZATION ENDOFSTUDYENDOFSTUDY Primary Endpoint: Time to first on-study skeletal-related event (SRE) (Non-inferiority) Denosumab 120 mg SC and Placebo IV* every 4 weeks (n=2862) Zoledronic acid 4 mg IV* and Placebo SC every 4 weeks (n=2861)

76 Baseline Characteristics Characteristics, n (%) or Median (Q1, Q3) Denosumab (n=2862) Zoledronic Acid (n=2861) Tumor type † Breast1026 (36)1020 (36) Prostate 950 (33) 951 (33) Non-small cell lung 350 (12) 352 (12) Multiple myeloma 87 (3) 93 (3) Renal70 (2)85 (3) Small cell lung61 (2)48 (2) Bladder28 (1)35 (1) Rectal25 (1)35 (1) Colon30 (1)29 (1) Other § 449 (16) 445 (16) Lipton A, Fizazi K, Stopeck A, et al. Eur J Cancer 2012

77 Primary Endpoint: Time to First On-Study SRE Patients at Risk: Denosumab Zoledronic Acid Month Proportion without SRE HR 0.83 (95% CI: 0.76, 0.90) P<0.001 (Superiority) KM Estimate of Median Months Denosumab27.66 Zoledronic Acid19.45 Risk Reduction 17% Lipton A, Fizazi K, Stopeck A, et al. Eur J Cancer 2012

78 Time to First and Subsequent On-Study SRE Month HR 0.82 (95% CI: 0.75, 0.89) P<0.001 (Superiority) Risk Reduction 18% Cumulative Mean Number of SRE Total Number of Events Denosumab1360 Zoledronic Acid1628 Lipton A, Fizazi K, Stopeck A, et al. Eur J Cancer 2012

79  Quali criteri vengono utilizzati per scegliere il farmaco da utilizzare in prima linea ?  Come monitorizzare la terapia ? Criteri di successo/insuccesso  La gestione delle complicanze/effetti collaterali  Trattamento delle metastasi ossee  Associazione di farmaci ? terapie sequenziali ?

80 Why Combine? Mechanistically “Vertically” block a pathway “Horizontally” block multiple pathways Goals increase response rates and prolong PFS Why Sequence? Mechanistically target resistant pathways upregulated by prior therapy Goals maintain prolonged disease stability decrease toxicity by diminishing drug interactions Combination or Sequential Therapy

81

82 What are we looking for ? 1Maior increases in response rate over monotherapy 2Ability to achieve a CR from therapy or in conjunction with metastasectomy 3Relative tolerability

83 Combination Therapy Antiangiogenic therapy combinations -Sorafenib plus bevacizumab (Sosman et al. JCO 2006) -Sorafenib and AMG 386 (Rini et al. JCO 2011) -Sunitinib plus Bevacizumab (Feldman et al. JCO 2009) Antiangiogenic therapy-mTOR inhibitor combinations - Sunitinib plus Temsirolimus (Patel et al. Clin Genitourinary Cancer 2009) -Bevacizumab plus Temsirolimus ( Merchan et al JCO 2007 abstract 5034; Escudier et al. JCO 2011 abstract 4516 ) Immunotherapy-Antiangiogenic therapy combinations -Sunitinib+IFN (Motzer et al. Clin Genitourinary Cancer 2009) -Sorafenib+ IFN (Jonasch et al. Cancer 2010) -Bevacizumab+ IFN (Rini et al, JCO 2008)

84 Combinations of Targeted Agents in mRCC: Sunitinib Combinations

85 Combinations of Targeted Agents in mRCC: Sorafenib Combinations

86 Combinations of Targeted Agents in mRCC: Bevacizumab Combinations

87 Sequenzial therapy: goals 1Maximize efficacy and duration of first-line agent 2Minimize toxicity 3Choose both initial and subsequent therapy on the basis of robust predictive biomarkers

88 Attenzione ai confronti indiretti! RECORD-1 (everolimus) AXIS (axitinib) Accrual disease12/ /20079/2008-7/2010 ComparatorPlaceboSorafenib 2 or more prior therapies (TKI)26%0% MSKCC poor-risk14%33% Allowed TKI-intolerant patientsYesNo Allowed crossoverYesNo Allowed dose esclationNoYes Only prior sunitinibN=43, 13% of ptsN=194, 26% of pts RECORD-1 vs AXIS: trial design discrepancies

89 [TITLE] Presented By Thomas Powles, MD at 2013 ASCO Annual Meeting

90 [TITLE]

91

92

93

94 TKI mTOR Ongoing clinical trials will solve all our doubts …

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109


Scaricare ppt "Scuola di uro Oncologia G. Cartenì Direttore U.O.S.C. di Oncologia Medica A.O.R.N. A. Cardarelli Napoli Roma, 12/13 Luglio 2013 CONTROVERSIE ONCOLOGICHE."

Presentazioni simili


Annunci Google