Management of advanced prostate cancer in senior adults: a booming area

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1 Management of advanced prostate cancer in senior adults: a booming area Matti Aapro Multidisciplinary Oncology Institute Genolier, Switzerland July 2014 version

2 Management of advanced prostate cancer in senior adults: a booming area Matti Aapro Multidisciplinary Oncology Institute Genolier, Switzerland July 2014 version

3 Disclosures Invited speaker / advisory boards Sanofi Amgen GlaxoSmithKline Hoffmann-Laroche Ferring Ipsen Janssen Novartis Pfizer Sandoz 3

4 Treatment options for advanced Prostate Ca in senior adults Castration-sensitive metastatic prostate cancer (mcspc): hot from ASCO and Lancet. NOT AN APPROVED INDICATION. Castration-resistant metastatic prostate cancer (mcrpc) Palliative therapy for bone metastases SIOG guidelines 4

5 E3805 (CHAARTED) - Chemo-Hormonal vs Androgen Ablation Randomized Trial in Extensive Disease Stratify: Extent of mets High vs Low Age 70 vs <70 ECOG PS 0-1 vs 2 CAB >30 days Yes vs No Prior adjuvant hormonal Tt > 12 vs 12 mo SRE prevention Yes vs No R A N D O M I Z E N = 780 ADT + Docetaxel (75mg/m 2 ) for 6 cycles without prednisone ADT alone ADT allowed up to 120 days prior to randomization Intermittent ADT dosing not allowed Follow-up to time to progression and OS Chemotherapy at investigator s discretion at progression Sweeney C et al. ASCO 2014 LBA2 ADT: Androgen Deprivation Therapy; OS: overall survival; CAB: ;complete androgen blockade SRE: skeletal related events; PS: performance status

6 E3805 (CHAARTED) - Chemo-Hormonal vs Androgen Ablation Randomized Trial in Extensive Disease ADT allowed up to 120 days prior to randomization Intermittent ADT dosing not allowed Sweeney C et al. ASCO 2014 LBA2 ADT: Androgen Deprivation Therapy; D: docetaxel (75mg/m2 without prednisone for 6 cycles)

7 E3805 (CHAARTED) - Chemo-Hormonal vs Androgen Ablation Randomized Trial in Extensive Disease Sweeney C et al. ASCO 2014 LBA2 ADT: Androgen Deprivation Therapy; D: docetaxel (75mg/m2 without prednisone for 6 cycles)

8 E3805 (CHAARTED) - Chemo-Hormonal vs Androgen Ablation Randomized Trial in Extensive Disease Sweeney C et al. ASCO 2014 LBA2 ADT: Androgen Deprivation Therapy; D: docetaxel (75mg/m2 without prednisone for 6 cycles)

9 NO PATIENT ABOVE AGE 68.study from 2004 to 2008 GETUG-15 Presented By Michael Morris at 2014 ASCO Annual Meeting

10 Comparison to GETUG15 Presented By Michael Morris at 2014 ASCO Annual Meeting

11 Treatment options for advanced Prostate Ca in senior adults Castration-sensitive metastatic prostate cancer (mcspc) Castration-resistant metastatic prostate cancer (mcrpc) Palliative therapy for bone metastases SIOG guidelines 11

12 Androgen deprivation therapy in advanced PCa: Specific considerations for senior adults First-line ADT in monotherapy is the standard of care Maximum androgen blockade results in a small advantage in OS, which is not clinically relevant Maximum androgen blockade increases side effects and has significant effects on QoL Prostate Cancer Trialists Collaborative Group. Lancet 2000;355: ADT: Androgen Deprivation Therapy; OS: overall survival; QoL: quality of life 12

$Androgen deprivation therapy: adverse events Bone loss with increased risk of Increased risk of diabetes 3 fracture 1,2 Increased risk of fatal cardiac events 4 6 Baseline bone density Cumulative$

13 Androgen deprivation therapy: adverse events Bone loss with increased risk of Increased risk of diabetes 3 fracture 1,2 Increased risk of fatal cardiac events 4 6 Baseline bone density Cumulative fracture incidence (%) Prevent risk of osteoporosis Orchiectomy No orchiectomy Years 1. Daniell et al. J Urol 1997;157: Shahinian VB et al. N Engl J Med 2005;352: Keating NL et al. J Clin Oncol 2006;27: Caution in patients with: History of stroke Chronic heart failure Myocardial infarction LESS IS BETTER! 4. D Amico et al. J Clin Oncol 2007;25: Hayes et al. BJU Int 2010;106: Nguyen et al. Int J Radiat Oncol Biol Phys 2012;82:1411-

14 Management of advanced PCa: Specific considerations for senior adults (2/4) Castration-sensitive metastatic prostate cancer (mcspc) Castration-resistant metastatic prostate cancer (mcrpc) Docetaxel 3-weekly schedule is the standard of care 1* Weekly or bi-weekly schedule for frail patients? 2-3 Cabazitaxel Abiraterone acetate Enzalutamide Sipuleucel-T Palliative therapy for bone metastases SIOG guidelines 1. Berthold D et al. J Clin Oncol2008;26: Droz JP et al. BJU Int2010;106: Kellokumpu-Lehtinen P et al. Lancet Oncol 2013;14:

15 Docetaxel: age does not affect survival (TAX 327) Hazard ratio in favour of Docetaxel+P Mitoxantrone+P ITT Age < 65 years Age 65 years Age 75 years Pain: no Pain: yes KPS 80 KPS 70 Among men 75 years, 3-weekly Docetaxel+P resulted in more dose reductions than weekly schedule (22% versus 8%, p = 0.007) but tolerability was otherwise comparable. Both Docetaxel schedules were associated with more favorable efficacy than mitoxantrone Tannock IF et al. N Engl J Med 2004;351: ; Horganet al. J. GeriatrOncol2014; 5: P: prednisone 15

16 Phase 2 study of weekly docetaxel +prednisolone vs prednisolone alone in mcrpc Docetaxel weekly + Prednisolone Prednisolone Toxic outcomes N PFS(median) [95% CI] OS(median) [95% CI] Survival rate (%) 1-year 2-year 12-week PSA response rate QoL improvement Physical function Pain Fatigue Nausea/vomiting Global QoL 11 months [ ] 27 months [ ] 82% 61% 4 months [ ] 18 months [ ] 67% 29% 69% 36% 27% 52% 38% 17% 27% 3% 16% 29% 8% 16% Gastrointestinal: grade 2 Nausea Vomiting Diarrhoea Other/Constitutional: grade 2 Nail changes Alopecia Conjunctivitis/tearing Fatigue/Anorexia Peripheral neuropathy Atrial flutter Fluid retention Median age 70 years No cross-over Fossa SD et al. Eur Urol 2007;52: mcrpc: metastatic castrate-resistant prostate cancer; OS: overall survival; PFS: progression-free survival; QoL: quality of life 16

17 Phase 3 study of bi-weekly versus 3-weekly docetaxel plus prednisone in mcrpc Efficacy Grade 3 toxicities Docetaxel bi-weekly + P (n=170) Docetaxel 3-weekly + P (n=169) p Docetaxel bi-weekly + P (n=170) Docetaxel 3-weekly + P (n=169) TTTF(median) [95% CI] OS(median) [95% CI] 5.6 mo [ ] 19.5 mo [ ] 4.9 mo [ ] 17 mo [ ] Hematological - Neutropenia - Leucopenia - Anemia - Thrombocytopenia - Febrile neutropenia 36% 13% 1% 1% 4% 53% 29% 1% 0 14% PSA response 49% 42% 0.49 Non-hematological Best clinical response - CR or PR - Stable - Progression 23% 46% 8% 22% 46% 11% Fatigue - Infection without neutropenia - Neutropenic infection - ALP - Diarrhea - Nausea 15% 11% 6% 9% 1% 1% 15% 12% 24% 6% 2% 1% Kellokumpu-Lehtinen P et al. Lancet Oncol 2013;14: mcrpc: metastatic castrate-resistant prostate cancer; TTTF: Time to Treatment Failure: OS: overall survival ALP: Alkaline phosphatase 17

18 MATuRITY: Prospective registry in men aged 70+ with mcrpc Docetaxel Grade 3 toxicity % At 6 months Taxane (N=140) Non-taxane (N=193) OS rate 91% 81% PFS 66% 50% <0.001 Best clinical benefit 60% 36% <0.001 PSA 50% 52.5% 37.4% mg/m 2 q3w in 83.9% of cases Hormonal manipulations or non-taxane chemotherapy P Fatigue 17.1% Nausea/vomiting 14% Neutropenia Febrile neutropenia 9.8% 2.6% Sensory neuropathy 9.3% Diarrhea 8.8% Anemia 7.8% Loss of appetite 7.3% Nail change 6.7% Droz JP et al. ESMO 2012;Poster 934P 18

Cabazitaxel significantly improves survival vs mitoxantrone (TROPIC, post-docetaxel) 100 % surviving 90 80 70 60 50 40 30 Mitoxantrone+P Cabazitaxel+P HR 0.72 (95% CI: 0.

19 Cabazitaxel significantly improves survival vs mitoxantrone (TROPIC, post-docetaxel) 100 % surviving Mitoxantrone+P Cabazitaxel+P HR 0.72 (95% CI: ) P< Time (months) 755 patients with mcrpc who progressed during or after docetaxel BahlA Annalsof Oncol2013; 24: P: prednisone 19

Cabazitaxel (TROPIC): Survival not influenced by age N Favors CABA+P Favors MITO+P HR (95% CI) All randomized patients 755 0.70 (0.59 0.83) ECOG status: 0,1 694 0.68 (0.57 0.82) ECOG status: 2 61 0.

75 (0.55 1.02) Age<65 years 295 0.81 (0.61 1.08) Age 65 years 460 0.62 (0.50 0.78) Pain at baseline: no 314 0.57 (0.43 0.77) Pain at baseline: yes 310 0.76 (0.59 0.

20 Cabazitaxel (TROPIC): Survival not influenced by age N Favors CABA+P Favors MITO+P HR (95% CI) All randomized patients ( ) ECOG status: 0, ( ) ECOG status: ( ) Measurable disease: no ( ) Measurable disease: yes ( ) Number of previous chemotherapies: ( ) Number of previous chemotherapies: ( ) Age<65 years ( ) Age 65 years ( ) Pain at baseline: no ( ) Pain at baseline: yes ( ) Rising PSA at baseline: no ( ) Rising PSA at baseline: yes ( ) Progression during docetaxel treatment ( ) Progression <3 months after docetaxel ( ) Progression 3 months after docetaxel ( ) de Bono et al. Lancet 2010;376: ECOG: Eastern Cooperative Oncology Group; CABA+P: cabazitaxel+prednisone; MITO+P: mitoxantrone+prednisone 20

21 Cabazitaxel(Europeancompassionateuse program) - Safety in senior adults <70 years (n=238) years (n=100) 75+ years (n=88) Treatment exposure - N cycles, median (range) - Dose delay for drug-related AE Dose reduction for any cause - G-CSF primary prophylaxis (C1) 4 (1-16) 4.3% 18.5% 39.2% 4 (1-12) 13.0% 16.0% 46.1% 4 (1-11) 5.7% 15.9% 50.3% Hematological, grade 3 - Neutropenia - Leucopenia - Anemia - Febrile neutropenia - Neutropenic sepsis 15.0% 6.2% 5.0% 5.2% 1.0% 16.7% 8.3% 4.4% 5.6% 1.6% 23.4% 9.7% 4.1% 5.5% 1.4% Non-hematological, grade 3 - Fatigue - Asthenia - Diarrhea - Nausea - Vomiting - Hematuria - Peripheral neuropathy - Nail disorders 4.0% 1.4% 3.3% 0% 1.0% 0.5% % 4.4% 1.7% 0.6% 1.1% 2.8% % 5.5% 2.8% 3.4% 2.1% 1.4% 0.7% 0 HeidenreichAet al. EurJ Cancer 2014; 50;

22 Abiraterone in post-docetaxel setting significantly improves survival vs placebo (COU-AA-301) Overall survival (%) Median age: 69 years 75 years: 28% Placebo+P 11.2 months Abiraterone acetate+p 15.8 months HR 0.74 (95% CI: ) P< Time to death (months) 1195 patients with mcrpc who were previously treated with docetaxel Fizazi K et al. Lancet Oncol 2012;13(10); P: prednisone; HR: hazard ratio; CI: confidence interval 22

Abiraterone (COU-AA-301) Survival not influenced by age Subgroup AA+P Median (mo) Placebo+P Median (mo) Favors AA+P Favors Placebo+P HR (95% CI) Baseline ECOG PS* 0 1 2 17.0 7.3 12.3 7.0 0.74 (0.63 0.

23 Abiraterone (COU-AA-301) Survival not influenced by age Subgroup AA+P Median (mo) Placebo+P Median (mo) Favors AA+P Favors Placebo+P HR (95% CI) Baseline ECOG PS* ( ) 0.77 ( ) Baseline BPI-SF score* < ( ) 0.78 ( ) Number of CT regimens* ( ) 0.80 ( ) Type of progression* PSA only Radiographic ( ) 0.78 ( ) Age (years) < ( ) 0.76 ( ) 0.64 ( ) Visceral disease at entry Yes No ( ) 0.69 ( ) Baseline PSA >median Yes No ( ) 0.79 ( ) Baseline LDH >median Yes No ( ) 0.75 ( ) Baseline ALK-P >median Yes No ( ) 0.88 ( ) Fizazi K et al. Lancet Oncol 2012;13(10); BPI-SF: Brief Pain Inventory Short Form; CI: confidence interval; ECOG: Eastern Cooperative Oncology Group; LDH: lactate dehydrogenase; OS: overall survival; PSA: prostate-specific antigen 23

24 Abiraterone in chemo-naïve patients significantly improves rpfsbut only trend for OS Radiological PFS Overall survival PFS (%) Prednisone 8.3 mths HR 0.53 (95% CI ) P<0.001 Abiraterone + P 16.5 mths Months OS (%) Prednisone 27.2 mths HR 0.75 (95% CI ) P= Months Abiraterone + P Not reached Prespecified P for significance Asymptomatic or mildly symptomatic chemo-naïve patients without visceral metastases 1088 chemonaive mcrpc patients RyanC et al. N EnglJ Med 2013; 368: PFS: progression-free survival; P: prednisone 24

Enzalutamide in post-docetaxel setting significantly improves survival vs placebo (AFFIRM) Survival (%) 100 90 80 70

25 Enzalutamide in post-docetaxel setting significantly improves survival vs placebo (AFFIRM) Survival (%) Median age: 69 years 75 years: 25% Placebo OS 13.6 months ] Enzalutamide OS 18.4 months HR (95% CI: ) P< Duration of overall survival (months) 1199 patients with mcrpc previously treated with docetaxel Scher HI et al.n EnglJ Med 2012;367: NYR: not yet reached;os: overall survival

26 Enzalutamide in chemo-naïve patients significantly improves rpfs and OS PFS (%) Radiological PFS HR (95% CI ) P<0.001 Enzalutamide NYR Placebo 3.9 mths 100 Survival (%) Overall survival Placebo 30.2 mths HR (95% CI ) P< Enzalutamide 32.4 mths Asymptomatic or mildly symptomatic chemo-naïve mcrpc 1717 chemonaive mcrpc patients; visceral metastases 11% RyanC et al. N EnglJ Med 2013; 368: PFS: progression-free survival; P: prednisone 26

27 Enzalutamide (AFFIRM) Survival not influenced by age Subgroup Favors Enzalutamide Favors Placebo HR for death (95% CI) Median OS (months) Enzalutamide/Placebo All subjects 0.63 ( ) 18.4/13.6 Age (years) <65 >65 Baseline ECOG PS score Baseline mean pain score on BPI-SF Geographic region Number of prior chemotherapy regimens Type of progression at study entry Baseline value >median value <4 4 North America Other 1 2 PSA only PSA ±Radiographic PSA LDH 0.63 ( ) 0.63 ( ) 0.62 ( ) 0.65 ( ) 0.59 ( ) 0.71 ( ) 0.63 ( ) 0.64 ( ) 0.59 ( ) 0.74 ( ) 0.62 ( ) 0.64 ( ) 0.62 ( ) 0.61 ( ) / /13.9 / /7.2 / / /12/3 /14.4 / /12.3 / / / /8.5 Scher HI et al. N EnglJ Med 2012; 367: BPI-SF: Brief Pain Inventory Short Form; CI: confidence interval; ECOG: Eastern Cooperative Oncology Group; LDH: lactate dehydrogenase; OS: overall survival; PSA: prostate-specific antigen

28 Specific considerations for senior adults with VERY advanced disease Cabazitaxel *1 Higher risk of febrile neutropenia(7.5 vs 1.3%) Consider primary prophylaxis with G-CSF in high risk patients 4 Higher risk of diarrhea (6.5 vs0.3% grade 3) Rehydration with antiemeticsand antidiarrheals as needed Abiraterone *2 Hypokalemia, hypertension & fluid retention due to mineralocorticoid excess Use withcaution in patients with CV diseases Risk of adrenocortical insufficiency Caution if interruption of dailysteroidsand/or infection or stress Risk of hepatotoxicity Monitor liver function Enzalutamide 3 Higher risk of fatigue (34% vs29%) Evaluate functional status & program exercise support Risk of seizures(0.9%) Caution if history of seizure, brain injury, cerebral vascular accident, brain metastases Higher risk of hot flushes (20 vs10%) Higher risk of falls (4.6 vs 1.3%) Product information: 1. cabazitaxel, 2. abiraterone, 3. enzalutamide; Guidelines: 4. EORTC guidelines Aapro M et al. EJC 2011; 47: 8-32 and ASCO CV: cardiovascular; G-CSF: granulocyte colony-stimulating factor; * administered with prednisone 28

29 Sipuleucel-T significantly improves survival vs placebo (IMPACT trial, pre-docetaxel) Overall survival (%) n=512 Overall survival Placebo Sipuleucel-T Time (months) Main AEs: chills, fever, headache Median age: 72 years Hazard Ratio 0.78 (95% CI, ) P=0.03 Asymptomatic or mildly symptomatic chemo-naïve mcrpc Without visceral metastases KantoffPW et al. N Engl J Med 2010;363: mcrpc: metastatic castration-resistant prostate cancer; mths: months 29

30 Which drug for which patient? July 2014 version

31 Short response to first ADT may predict poor response to AR-targeted therapies AR targetedagents 1 Retrospective analysis in 108 patients with metastatic PCa Poor response to subsequent hormone therapies (including abiraterone, enzalutamide) if duration of response to first ADT < 16 months Durationof response < 16 mths 16 mths PSA 50% 18% 58% MedianOS - - Docetaxel 2 Post-hoc analysis of TAX327 randomized phase III trial 335 mcrpc patients treated with docetaxel+p (D) and 336 with mitoxantrone+p(m) Good response to docetaxel irrespective of duration of 1st ADT Durationof response < 15 mths 15 mths PSA 50% 62% 60% MedianOS benefit(d vs M) 3.5 mths 2.5 mths 1 LoriotY & FizaziK. EurUrol2013; 63: ; 2 van Soest R et al. ASCO 2014 (abstract5043) TTP: time to progression; mths: months; D: docetaxel plus prednisone; M: mitoxantrone plus prednisone

32 Percentage with PSA decrease 50% Extended metastatic spread and high NLR may predict poor response to abiraterone PSA response Median overall survival (months) 0 Restricted* Other Extended** 0 Restricted* mets & NLR 5 cases mets & NLR >5 mets & NLR 5 NLR: neutrophil/lymphocyte ratio; *Bone mets only or lymph node mets only; **visceral mets alone or combined with bone or lymph nodes Overall survival 30 Princess Margaret (test cohort, n=116) Royal Marsden (validation cohort, n=250) Other cases Extended** mets & NLR >5 Leibowitz-Amit et al., Annals Oncol 2014 (epub ahead of print)

33 Poor responseto abiraterone in patients progressing on enzalutamide (post-docetaxel) Loriot 1 Noonan 2 COU-AA Prior Enzalutamide Yes No Yes No Median PFS (months) Median OS (months) PSA 50%* 8% 29% 3% 29% *Confirmed by a second value; Loriot [1] and Noonan [2] are retrospective studies conducted in 38 and 30 patients,respectively OS: overall survival; PFS: progression-free survival LoriotY et al. Ann Oncol2013; 24: ; Noonan Kl et al. Ann Oncol2013; 24: ; FizaziK et al. Lancet Oncol2012; 13:

34 Poor responseto enzalutamide in patients progressing on abiraterone (post-docetaxel) *Confirmed by a second value; Schrader 1 Bianchini 2 Thomsen 3 Badrising 4 AFFIRM 5 Prior ABI Yes Yes Yes Yes No Partial response 2.9% 4.3% - 29% Median PFS, months Median OS, months ** PSA 50% 29% 13%* 17% 21% 54%* *Confirmed by a second value; **mean value 1. SchraderA et al. EurUrol2014;65:e22-3; 2. BianchiniD et al. EurJ Cancer2013 (epubaheadof print) 3. Thomsen FB ScandJ UrolNephro2013 (epubahead) ; 4. BadrisingS. et al. Cancer2014;120:968-75); 5. ScherHI et al. Lancet Oncol2012; 13:

35 Management of advanced PCa: specific considerations for senior adults (3/4) Castration-sensitive metastatic prostate cancer (mcspc) Castration-resistant metastatic prostate cancer (mcrpc) Palliative therapy for bone metastases Zoledronic acid Denosumab Interventionnal radiology ( vertebroplasty, kyphoplasty) Radiation therapy Radium-223 SIOG guidelines 35

36 Radium-223 improves survival vs placebo (ALSYMPCA, post-docetaxel) Mean age: 70 years Hazard Ratio (95% CI, ) P= % Placebo (N=307) Median OS: 11.3 months Radium-223 (N=614) Median OS: 14.9 months Time to death(months) 921 patients with symptomatic mcrpc post-docetaxel (or unfit for chemotherapy), 2 bone mets, no visceral mets Parker C et al. N EnglJ Med 2013;369:213-23

38 SIOG 2014 prostate guidelines Matti Aapro Multidisciplinary Oncology Institute Genolier, Switzerland

39 SIOG recommendations for senior adults 1. DrozJP et al. CritRev OncolHematol2010;73: DrozJP et al. BJU Int2010;106:

40 SIOG recommendations for senior adults Treatment recommendations for older men with prostate cancer should be based on: Health status (mainly driven by co-morbidities) AND Patient preferences NOT Chronological age 1. DrozJP et al. CritRev OncolHematol2010;73: DrozJP et al. BJU Int2010;106:

41 G-8 geriatric screening tool A. Has food intake declined over the past 3 months due to loss of appetite, digestive problems, chewing or swallowing difficulties? B. Weight loss during the last 3 months? C. Mobility? D. Neuropsychological problems? 0 = severe decrease 1 = moderate decrease 2 = no decrease 0 = >3kg 1 = does not know 2 = between 1 &3 kg 3 = none 0 = bed or chair bound 1 = able to get out of bed/chair but does not go out 2 = goes out 0 = severe dementia or depression 1 = mild dementia 2 = no psychological problems Cut-off value = 14 14: favourable 14: impairment which requires comprehensive geriatric evaluation E. BMI (weight in kg/height in m²) F. Takes more than three prescription drugs per day? G. In comparison with other people of the same age, how does the patients consider his/her health status? H. Age Total score 0 = BMI<19 1=BMI 19to <21 2= BMI 21 to <23 3 = BMI 23 0 = yes 1 = no 0.0 = not as good 0.5 = does not know 1.0 = as good 2.0 = better 0 = >85 yr 1= yr 2 = <80 yr 0-17 A fast test Median 4 4 (± 2.8) minutes for completion 98 7% completion rate in less than 10 min BellaraCA etal. AnnalsOncol2012; 23:

42 G8 screening >14 No geriatric assessment requested 14 Geriatric assessment requested Reversible: Abnormal ADL: 1 or 2 Malnutrition Depression Comorbidities CISR-G grades 1-2 Not reversible: Abnormal IADL Abnormal ADL 3 Severe malnutrition Cognitive impairment Comorbidities CISR-G grades 3-4 GERIATRIC INTERVENTIONS FIT VULNERABLE FRAIL 42

43 Principles of the guideline for PCa Health status evaluation Group 1 (Healthy) Group 2 (Vulnerable, i.e. reversible problem Group 3 (Frail, i.e. non reversible problem) Group 4 (Terminal illness) Geriatric Screening with G-8 tool Standard treatment as for younger patients Standard treatment as for younger patients Symptomatic management including adapted specific treatments Only palliative treatment Readaptation 1. Droz JP et al. CritRevOncolHematol2010;73: Droz JP et al. BJU Int 2010;106:

EAU and NCCN recommend therapy of early asymptomatic disease in all patients with life expectancy > 10 years Median life expectancy (years) 20 18 16 14 12 10 8 6 4 2 0 18 12.4 6.7 14.2 9.3 4.9 10.8 6.7 3.

44 EAU and NCCN recommend therapy of early asymptomatic disease in all patients with life expectancy > 10 years Median life expectancy (years) Should be considered for therapy: Fit and vulnerable aged years Only fit aged years years 75 years 80 years 85 years 90 years 95 years Top 25th percentile 50th percentile Lowest 25th percentile Walter LC et al. JAMA 2001;285:

45 EAU / SIOG 2014 guidelines Individualized treatment and life expectancy evaluation is mandatory Mottet N et al. EAU guidelines 2014 ( Droz JP, et al. Lancet Oncol 2014 (In press)

46 Overall conclusions Docetaxel (without prednisone) provides benefit versus ADT alone in metastatic hormone-naive PCa (unapproved indication ) Many new drugs to manage metastatic CRPC in senior adults, representing a significant increase in health care expenditure Optimal timing, sequencing and potential combinations of these new agents remain to be determined Need to rely on currently available predictors of response to each drug to optimize patient management

48 DECEMBER 5: A JOINT MASCC SIOG SESSION Chairs: D. Keefe (AUS) ; G. Zulian (CH) Bone health: a key factor in elderly and not so elderly patients with cancer M. Aapro (CH) Mucositis and new drugs: to prevent or to treat?d. Keefe (AUS) Depression: an issue in survivorship for elderly cancer patients. L. Balducci (USA) Ovarian cancer: issues in the long term for elderly patients C. Steer (AUS)

49 Matti Aapro IMO Genolier (Switzerland) THANK YOU MERCI 49

50 Any questions? 50

2014 Treatment Paradigms in mcrpc Docetaxel in hormone sensitive PC

Ronald de Wit Erasmus MC Cancer Institute The Netherlands 2014 Treatment Paradigms in mcrpc Docetaxel in hormone sensitive PC Disclosures Sanofi ; research grant support, consultancy and speaker fees Astellas;