Marcello Tucci SCDU Oncologia Medica Azienda Ospedaliero Universitaria San Luigi di Orbassano Università degli studi di Torino mCRPC 2014 TRA EVOLUZIONE E RIVOLUZIONE: COME ORIENTARSI NEL LABIRINTO DELLE TERAPIE IL CARCINOMA PROSTATICO, UNA MALATTIA ETEROGENEA? RAZIONALE E RISULTATI DEL TRATTAMENTO CHEMIOTERAPICO ASSOCIATO ALL’ANDROGENO-DEPRIVAZIONE
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mCRPC2014 TRA EVOLUZIONE E RIVOLUZIONE: COME …€¦ · Stomatitis 1 ‐‐ Neuropathy‐motor 1 ‐‐ Neuropathy‐sensory 1 ‐‐ Thrombo‐embolism
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Marcello Tucci
SCDU Oncologia MedicaAzienda Ospedaliero Universitaria San Luigi di Orbassano
Università degli studi di Torino
mCRPC 2014 TRA EVOLUZIONE E RIVOLUZIONE:COME ORIENTARSI NEL LABIRINTO DELLE TERAPIE
IL CARCINOMA PROSTATICO,UNA MALATTIA ETEROGENEA?
RAZIONALE E RISULTATI DEL TRATTAMENTO CHEMIOTERAPICO ASSOCIATO ALL’ANDROGENO-DEPRIVAZIONE
Tombal. B. Eur J Cancer 2011;47:S179‐188ADT: Androgen Deprivation Therapy; AR: androgen receptor; mets: metastases
The CHAARTED hypothesis
Sweeney C et al. J Clin Oncol 2014;32(June 20 suppl):abstract LBA2ADT: Androgen Deprivation Therapy; AR: androgen receptor
AR independent clones
ADT + Docetaxel
ADT
AR independent clones AR dependent clones
<br /><br />E3805<br />CHAARTED: ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
E3805 – CHAARTED study
Sweeney C et al. J Clin Oncol 2014;32(June 20 suppl):abstract LBA2. ADT: androgen deprivation therapy; Mets: Metastases; PS: Performance Status; SRE: Skeletal Related Events; CAB: Complete Androgen Blockade; docétaxel (75mg/m2 every 21 days)
• Open‐label, multicenter, phase III trial conducted in US• Standard dexamethasone premedication but no daily prednisone
ARM A (n=397)ADT + Docetaxelfor 6 cycles
ARM B (n=393) ADT
Follow for time to progression and overall survival
Chemotherapy at investigator’s discretion at progression
Newly diagnosed M1 PCa
Key stratification
• Extent of mets(High vs low)
• Age(≥70 vs < 70 y)
RANDOMIZE
1. Eisenberg M et al. N Engl J Med 1988;339:1036‐42; 2. Crawford E et al. N Engl J Med 1989;321:419‐24;3. Hussain M et al. N Engl J Med 2013;368:1314‐25; 4. Millikan E et al. J Clin Oncol 2008;26:5936‐42
High volume disease is prognostic in metastatic hormone sensitive prostate cancer
Study endpoints• Primary endpoint:
– Overall survival
• Secondary endpoints:– Rate of PSA < 0.2 ng/mL at 6 months and 12 months– Time to biochemical, radiographic or symptomatic progressive disease (PD)
– Time to radiographic or symptomatic PD– Define adverse event profile and tolerability– Quality of life (FACT‐P) until 12 months after randomization
Sweeney C et al. J Clin Oncol 2014;32(June 20 suppl):abstract LBA2PSA: Prostate Specific Antigen; PD: Progressive Disease
CHAARTED Key eligibility criteria
• High volume metastatic disease:– visceral metastases and/or – 4 or more bone metastases (with at least 1 beyond pelvis and
vertebral column)
• At study initiation, only patients with high volume disease were to be accrued– Study amendment to allow patients with low volume
to be enrolled, with stratification on disease volume
Sweeney C et al. J Clin Oncol 2014;32(June 20 suppl):abstract LBA2. ADT: androgen deprivation therapy;
Is high volume disease definitionbased on robust data?
Patient characteristics (1)
Sweeney C et al. J Clin Oncol 2014;32(June 20 suppl):abstract LBA2Mets: Metastases; ADT: androgen deprivation therapy; Docetaxel 75mg/m²