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Working Group (PCWG)-2 guidelines recommend time to clinical or radiographic
event endpoints, and discouraged use of endpoints using PSA changes. We
investigated the association of progression defined by PCWG-2 guidelines and overall
survival (OS).
Methods: Two trials were analyzed: CS-205, a randomized phase II trial (n = 221)
comparing first-line docetaxel-prednisone (DP) plus AT-101 or placebo, and
SUN-1120 (n = 873), a phase III trial comparing prednisone plus sunitinib (SP) or
placebo (PP) following docetaxel-based chemotherapy. Both trials continued
therapy until progression defined by PCWG-2 criteria and OS was the primary
endpoint. OS was derived by the Kaplan-Meier method. Cox proportional hazards
regression models were used to estimate the effect of progression on OS. Landmark
analyses at 2-month intervals compared patients with prior progression with those
without progression. Sub-analyses compared patients removed from trial for
progression vs. other reasons and examined the association of type of progression
with OS.
Results: Patients who had previously progressed had an increased risk of death.
In CS-205, the hazards ratio (HR) ranged from 2.31 to 3.43 between landmark
times of 6 to 12 months and in SUN-1120 HR was 2.75 to 5.21 between
landmark times from 2 to 8 months. Median OS was 5.5 versus 14.4 months in
CS-205 beyond month 6 and 7.1 versus 16.1 months in SUN-1120 beyond
month 2 for those with/without prior progression. The types of progression
associated with OS varied between the trials. Patients removed from study due to
progression (excluding death) had a significantly worse OS than those coming off
for other reasons (HR: 1.90, 95% CI: 1.26-2.87 in CS-205 and HR: 1.23, 95% CI:
1.02-1.48 in SUN-1120).
Conclusions: Progression by PCWG-2 criteria was significantly associated with
decreased OS in patients receiving first-line docetaxel-based chemotherapy or
post-docetaxel therapy. Further validation will facilitate the employment of PCWG-2
defined progression as an intermediate endpoint.
Disclosure: G. Sonpavde: Research support to institution from Ascenta Therapeutics
and Pfizer, Inc, B.A. Wood: Employee of Ascenta Therapeutics, S. Wang: Employee
of Pfizer, Inc, J. Paolini: Employee of Pfizer, Inc, M. Lechuga: Employee of Pfizer,
Inc, M.R. Smith: Research support to institution from Pfizer, Inc, M.D. Michaelson:
Research support to institution from Pfizer, Inc, All other authors have declared no
conflicts of interest.
902P PREVALENCE OF NON-METASTATIC
CASTRATION-RESISTANT PROSTATE CANCER IN EUROPE
A. Liede 1 , O. Günther 2 , B. Bennett 3 , S. Wong 3
1 24-2-A, Amgen Inc., Thousand Oaks, CA, UNITED STATES OF AMERICA,
2 Center for Observational Research, Amgen Ltd, Uxbridge, UNITED KINGDOM,
3 Oncosight, Plan A, Inc., Mountain View, CA, UNITED STATES OF AMERICA
Background: Non-metastatic (M0) castration-resistant prostate cancer (CRPC) is a
growing public health burden that has not been adequately quantified. The increased
incidence of prostate cancer (PC) in Europe in the last two decades is a result of
widespread prostate-specific antigen (PSA) screening, and associated with declines in
mortality and improved survival as more men are diagnosed with M0 disease. A
proportion of men with M0 PC will receive medical or surgical androgen deprivation
therapy (ADT). Many ADT-treated men eventually relapse to develop M0 CRPC,
characterized by rising PSA without evidence of metastases while on ADT. We report
results of a model to estimate the prevalence of M0 CRPC in key populations in
Europe.
Methods: The model uses age-specific incidence and survival data from
population-based national cancer registries to estimate 5-, 10-, and 20-year limited
duration prevalence of PC and M0 PC in each country, each year from 2008 to 2026.
ADT rates for M0 PC by country reported by the literature and IMS Oncology
Analyser and disease relapse and progression rates from the literature are applied
to estimate prevalence of ADT-treated and M0 CRPC subgroups.
Results: For EU-5 countries (France, Germany, Italy, Spain, and UK), the model
projects that 5-year prevalence of PC will increase from approximately 1.0 million in
2012 to 1.3 million in 2026 as a result of wider adoption of PSA testing and aging of
the populations. M0 PC, which comprises about 85% of total PC 5-year prevalence,
will increase from approximately 0.8 million in 2012 to 1.0 million by 2026. In 2012,
prevalence of M0 CRPC (4-7% of total PC, depending on ADT use in the M0
setting) in EU-5 is estimated to reach up to 70,000 with a projected increase to
110,000 patients by 2026.
Conclusion: This model provides the first understanding of how many men in
Europe are living with M0 CRPC. Although M0 CRPC represents a small subset of
the PC population, the model predicts an increase in the prevalence of M0 CRPC
over the next 14 years. As men with M0 CRPC have an increased risk of developing
metastases (particularly to bone) resulting in a shortened lifespan, these findings
highlight the need for clinical trials to establish standards of care for these patients,
and for new therapeutic options.
Disclosure: A. Liede: Employed by and own stock in Amgen Inc. The study was
funded by Amgen Inc.O. Günther: Employed by Amgen Ltd and own stock in
Amgen. The study was funded by Amgen Inc. B. Bennett: Consultant at Plan A, Inc.
S. Wong: Consultants at Plan A, Inc.
Annals of Oncology
903P IMPROVED SURVIVAL IN PATIENTS WITH METASTATIC
CASTRATION RESISTANT PROSTATE CANCER (MCRPC)
TREATED ON CLINICAL TRIALS
C. Pezaro, A.G. Omlin, D. Mukherji, S. Sandhu, D. Bianchini, A. Mulick Cassidy,
G. Maier, D. Olmos, G. Attard, J.S. de Bono
Prostate Targeted Therapy Group, The Royal Marsden NHS Foundation Trust
and Institute of Cancer Research ICR, Sutton, UNITED KINGDOM
Background: Median overall survival (mOS) in patients (pts) with mCRPC was
13-16 months (m) in the pre-docetaxel era. These data, obtained from clinical trials,
were used to construct currently available prognostic nomograms. We hypothesise
that these models no longer reflect survival. Pts and physicians urgently require
updated prognostic data on which to base management decisions.
Methods: Pts with mCRPC treated on Phase I-III and expanded access trials at our
institution were identified and data retrospectively collected. Predicted survival by
Halabi and Smaletz nomograms were compared to calculated survival using
Kaplan-Maier analysis. Cox model multivariate (MV) analysis used variables at
referral, including performance status (PS), Gleason (GS), prostate specific antigen
(PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), hemoglobin (Hb),
visceral disease and albumin.
Results: Between 2003 and 2011, 442 CRPC pts were treated on clinical trials. At
diagnosis median age was 62 years (y; 41.8 – 82.7) and 243 (55.0%) had metastatic
disease. Median interval from diagnosis to CRPC was 2.8y (0.2 – 21.7). At referral
259 pts (58.6%) were chemotherapy-naïve. Halabi and Smaletz models predicted
mOS from referral in chemo-naïve pts of 21m and 17m respectively, however the
observed mOS was 32m (95%CI 29– 38). Survival from CRPC was 43m (CI 37 – 46)
and 39m (CI 35 - 44) in pre- and post-chemo pts, respectively. In our MV model
using data from 225 evaluable pre-chemo patients, ALP (HR 2.65, p = 0.001), LDH
(HR 2.66, p = 0.018), albumin (HR 0.92, p = 0.002) and PSA (HR 1.31, p = 0.046)
were each prognostic after controlling for other variables, whereas Hb, PS, GS and
visceral disease did not show a statistically significant effect.
Conclusion: Our pts lived significantly longer than predicted by current nomograms.
This is likely due to development of effective new treatments. MV analysis confirmed
the importance of several previously identified prognostic factors. Survival data from
this large cohort of CRPC pts should encourage men considering clinical trial
participation. Previously developed nomograms no longer accurately predict survival.
Disclosure: C. Pezaro: Author is an ICR employee. The ICR has a commercial
interest in Abiraterone and PI3K and AKT inhibitors. D. Mukherji: Author is an ICR
employee. The ICR has a commercial interest in Abiraterone and PI3K and AKT
inhibitors. S. Sandhu: Author is an ICR employee. The ICR has a commercial
interest in Abiraterone and PI3K and AKT inhibitors. A. Mulick Cassidy: Author is
an ICR employee. The ICR has a commercial interest in Abiraterone and PI3K and
AKT inhibitors. G. Maier: Author is an ICR employee. The ICR has a commercial
interest in Abiraterone and PI3K and AKT inhibitors. D. Olmos: Author is an ICR
employee. The ICR has a commercial interest in Abiraterone and PI3K and AKT
inhibitors. G. Attard: Author is an ICR employee. The ICR has a commercial interest
in Abiraterone and PI3K and AKT inhibitors. J.S. de Bono: Author is an ICR
employee. The ICR has a commercial interest in Abiraterone and PI3K and AKT
inhibitors. All other authors have declared no conflicts of interest.
904P THE CHARACTERISTICS OF DIFFERENT PATTERN OF
METASTASES IN PATIENTS WITH CASTRATE RESISTANT
PROSTATE CANCER TREATED WITH TAXOTERE
CHEMOTHERAPY
S. Dixit1 , J. Tito1 , P. Afzal2 1
Oncology, Hull & East Yorkshire NHS Trust, Hull, UNITED KINGDOM,
2
Oncology, Diana Princess of Wales Hospital, Grimsby, Grimsby, UNITED
KINGDOM
Introduction: Many new agents are being tested in patients with castrate resistant
metastatic prostate cancer. Understanding the characteristics of different pattern of
metastases and their responses to taxotere chemotherapy may help in stratifying the
patients in different prognostic and predictive groups.
Methods: Based on the metastases observed on bone scan and CT- scan, before
starting chemotherapy, three metastatic patterns were identified. Metastases
predominantly limited to the bones with small volume lymph node metastases (bone
predominant), metastases limited to the bones (bones only), and metastases with
bulky lymphadenopathy without bone metastases (lymph nodes only). Median
survival and the distribution of known prognostic factors were analysed in these
three groups.
Results: Seventy eight patients with a median age of 70 (Range, 47-86) and a median
PSA of 174 (11-3000) had a median survival of 17 months (95% C.I. 13-20). Factors
associated with statistically significant shorter survival were symptomatic state,
haemoglobin, PSA level, the duration of hormone response, and three metastases
pattern. Gleason score and age were not significant. The median survival for three
metastatic pattern, bone predominant (32), bone only (35), and lymph node only
(11) metastases, were 12, 19 and 23 months respectively. The distributions of age,
Gleason score, PSA level before starting chemotherapy, and PSA response were not
ix298 | Abstracts Volume 23 | Supplement 9 | September 2012