Download the ESMO 2012 Abstract Book - Oxford Journals

Annals of Oncology
lymph nodes in 15 patients (38%) and visceral disease in 10 patients (26%)] were
included in the analyses. Three patients (8%) attained a PSA response, defined as a
decrease of >50% in PSA, confirmed after ≥ 4 weeks. A further six patients (15%)
had a 30% PSA decline. The median PFS was 2.7 months (95% CI: 2.2 -3.9). Six out
of 26 evaluable patients (23%) had a symptomatic response on pain score and
decrease of analgesic consumption. Treatment was well-tolerated. One patient
required discontinuation of abiraterone due to oedema and hypokalemia.
Conclusions: This study indicates that abiraterone has antitumor activity in patients
with mCRPC pretreated with docetaxel and MDV3100. Further prospective
evaluation of these agents administered in combination is now warranted (Richards J
et al, Cancer Research 2012).
Disclosure: C. Pezaro: All authors are ICR employees. The ICR has a commercial
interest in Abiraterone, G. Attard: All authors are ICR employees. The ICR has a
commercial interest in Abiraterone. K. Fizazi: PI and advisory board for Jansen and
Medivation, J.S. de Bono: All authors are ICR employees. The ICR has a commercial
interest in Abiraterone. JS de Bono has served as a paid consultant for J&J,
Sanofi-Aventis, Medivation, Astellas, AstraZeneca, Dendreon, Genentech, Pfizer,
GSK. All other authors have declared no conflicts of interest.
925P CLINICAL ACTIVITY OF ABIRATERONE ACETATE (AA) AFTER
PROGRESSION ON MDV3100 IN PATIENTS WITH
METASTATIC CASTRATION RESISTANT PROSTATE CANCER
(MCRPC)
K. Noonan 1 , S. Ellard 2 , K. Chi 3
1 Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, CANADA,
2 Medical Oncology, BC Cancer Agency - Centre for the Southern Interior,
Kelowna, BC, CANADA, 3 Oncology, Vancouver Cancer Centre, University of
British Columbia, Vancouver, BC, CANADA
Background: AA improves outcomes in patients with mCRPC through inhibition of
CYP17 and androgen synthesis. Recently MDV3100, an androgen receptor
antagonist has also been shown to improve overall survival from mCRPC in patients
progressing after docetaxel. The optimal sequencing for these agents and whether
induction of cross-resistance occurs is unknown.
Methods: Multi-centre retrospective review of all patients with mCRPC treated with
AA after progressing on MDV3100.
Results: 25 patients were identified from 3 centres in Canada. Baseline characteristics
at time of AA initiation included a median age of 72 years, metastases in bone,
lymph nodes and lung/liver were present in 88, 44 and 28% respectively, 36% of
patients were on opiates, median hemoglobin was 120 g/L, median alkaline
phosphatase was 144 U/L, and LDH was elevated in 28%. 100% had prior docetaxel
chemotherapy and 0% prior ketoconazole. Median duration of prior MDV3100 was
34 weeks (range 8-95), with 64% (16/25) having had a >30% decline in PSA and 32%
(8/25) having a rising PSA as best response. After AA, 21 patients were evaluable for
response. The median duration of treatment with AA was 12 weeks (range 0-80).
14% (3/21) had a >30% PSA decline. Of these 3 patients, 1 continues to respond at
84 weeks of follow-up, while the other 2 had a time to PSA progression (defined as a
25% increase from nadir and a minimum of 2ug/mL) of 18, and 21 weeks.
Interestingly, the 2 patients with PSA responses of 18 and 21 weeks on AA did not
respond to MDV3100. 81% (17/21) had a rising PSA as best response. No objective
responses were observed. Median time to progression (PSA, objective or
symptomatic) on AA was 14.6 weeks [CI 8.8-20.4] and median overall survival was
48.7 weeks.
Conclusions: In this study of patients progressing after MDV3100, treatment with
AA was associated with a modest response rate; however primary resistance to
MDV3100 may not preclude a response to AA. The clinical activity of MDV3100
after progression on AA should also be evaluated to assist in the determination of
the optimal sequencing of these agents.
Disclosure: All authors have declared no conflicts of interest.
926P SAFETY OF ABIRATERONE ACETATE (AA) IN PATIENTS WITH
CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND
CONCOMITANT CARDIAC RISK
G. Procopio 1 , E. Verzoni 1 , I. Testa 1 , S. Stagni 2 , S. Villa 3 , R. Valdagni 3
, F.G.M. De Braud 1
1 Medical Oncology, Istituto Nazionale dei Tumori di Milano, MILAN, ITALY,
2 Urology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY,
3 Radiotherapy, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY
Introduction: Abiraterone acetate (AA) is an inhibitor of extragonadal androgen
biosynthesis that prolongs overall survival in CRPC patients who have received a
chemotherapy including docetaxel. The most common adverse events related to AA
therapy were fluid retention, hypertension, hypokaliemia and cardiac disorders. No
safety data are available in patients with concomitant cardiac disease.
Methods: Metastatic CRPC patients were enrolled in this prospective study if they
were also suffering from a concomitant controlled cardiovascular disease. AA 1000
mg per day and prednisone 5 mg bid were administered orally until grade 3-4
adverse events (AE) or disease progression. The primary endpoint was the safety
profile while the secondary endpoints were progression-free survival and PSA
response.
Results: From April to September 2011, 46 CRPC patients with concomitant
cardiovascular disorders have been treated with AA. Main patients characteristics
were: median age 71 years (range 57-81); baseline mean PSA value 40 ng/ml
(6.32-995); the most common sites of disease were bone (33 pts, 81 %), lung (13 pts,
33%) and liver (6 pts, 15 %). All patients were previously challenged with at least 2
lines of hormone therapy and 1 chemotherapy regimen including docetaxel. The
most common pre-existing cardiac disorders were hypertension 24 (66%),
arrhythmias 4 (12 %), cardiac ischemia 4 (9 %) and conduction irregularity 2 (4 %).
Additionally 10 patients (27 %) had metabolic disorders including dyslipidemia and
hyperglycemia. AA was feasible without inducing grade 3-4 AE nor treatment
modification. The most common grade 1-2 AE were asthenia (27%), hypertension
(18%) and fluid retention (28%). After a median time of treatment of 10 months
(range 4-12 months) no dose modifications due to toxicity were required. No efficacy
data are still available.
Conclusions: Treatment with AA was feasible and well tolerated also in patients
suffering from cardiac comorbidities and risk factors for cardiovascular disease.
Disclosure: All authors have declared no conflicts of interest.
927P TIME TO PROGRESSION AND SAFETY RESULTS OF A
NONSPECIFIC CYTOCHROME-P 17 INHIBITOR AFTER
RESPONSE/STABILIZATION TO DOCETAXEL AS A
MAINTENANCE STRATEGY IN METASTATIC
CASTRATATION-RESISTANT PROSTATE CANCER
I. Gil-Bazo1 , E. Arevalo1 , A. Castillo1 , M.E. Zudaire1 , O.E. Carranza1 , J.P. Fusco1 ,
E. Castanon Alvarez1 , L. Zubiri1 , P. Martín1 , I. Gil-Aldea2 1
Department of Oncology, Clínica Universidad de Navarra, Pamplona, SPAIN,
2
Centro de Investigación Biomédica, Complejo Hospitalario de Navarra,
Pamplona, SPAIN
Background: The first-line treatment of metastatic castration-resistant prostate
cancer (mCRPC) consists of docetaxel-based chemotherapy. The median time to
progression (TTP) from chemotherapy initiation is 6-8 months (mo). Ketoconazole
is a nonspecific cytochrome-P 17 inhibitor (CYP17i) that blocks adrenal androgen
synthesis. Low-dose ketoconazole (LDK), (200 mg, t.d.s) has shown interesting
activity in mCRPC after progression to androgen deprivation. The role of a CYP17i
in the maintenance setting after response/stabilization to docetaxel has never been
studied.
Methods: Thirty-eight mCRPC patients showing progression to luteinizing-hormone
releasing hormone agonists (LHRHa), maintained LHRHa and received a median of
7 cycles of front-line three-weekly docetaxel (75 mg/m2) plus daily prednisone (10
mg). Twenty out of the thirty-eight patients showing no progression to docetaxel
were enrolled. After docetaxel, ten patients were assigned to LDK maintenance
treatment plus prednisone (10 mg/day) and LHRHa, and ten patients received
LHRHa alone. TTP was the primary endpoint.
Results: After 33 months follow-up, a median TTP from docetaxel initiation was
11.5 months (IC95%: 6.3-16.6) for maintenance therapy and 9.2 months (IC95%:
8.5-9.9) for the control arm p = 0.047). Maintenance treatment was well tolerated
with only one patient experiencing a grade 4 adverse event (non-symptomatic
pulmonary embolism). Grade 1 and 2 asthenia and hot flashes worsening were the
most common toxicities (table).
Conclusions: This is the first study testing a CYP17i for maintenance therapy after
response/stabilization to docetaxel. A more than 2 months significant benefit in TTP
with a favorable toxicity profile is observed. A further prospective analysis in a larger
series using a CYP17i is warranted.
Toxicity profile of maintenance therapy with a CYP17 inhibitor.
Grade Toxicity 1 2 3 4 5
Asthenia 3 2 - - -
Diarrhea 1 1 - - -
Hepatotoxicity 1 1 - - -
Hyporexia - 1 - - -
Cephalea 1 - - - -
Hot flashes 1 4 - - -
Fluid Retention 1 2 - - -
Pulmonary embolism - - - 1 -
Disclosure: All authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds400 | ix305