Download the ESMO 2012 Abstract Book - Oxford Journals

Annals of Oncology
on voluntary reporting, only a qualitative comparison to the safety profile observed
in the clinical trial setting is possible.
Methods: Safety information spontaneously reported to Sanofi US PV from June 17,
2010 - March 31, 2012 was reviewed. The most frequently reported AEs are
presented, using MedDRA preferred terms and compared with the safety profile
observed in clinical trials.
Results: A total of 692 spontaneously reported AEs were received for 373 US men in
the time period indicated, 312 (45%) serious (SAEs) and 380 (55%) non-serious. The
pts were 45 to 88 years old (mean ± SD: 68.6 ± 12) and virtually all with mCRPC.
The most frequently reported hematologic AEs were neutropenia [n = 27; 16 SAEs],
febrile neutropenia [n = 18; 17 SAEs], anemia [n = 9; 4 SAEs] and thrombocytopenia
[n = 7; 3 SAEs]. The most frequently reported non-hematologic AEs included
diarrhea [n = 32; 8 SAEs], fatigue [n = 28; 1 SAEs], hematuria [n = 15; 5 SAEs],
nausea [n = 14; 1 SAEs], vomiting [n = 9; 2 SAEs] and pyrexia [n = 3; 0 SAEs].
Concomitant therapies and co-morbidities were associated with most of the cases.
Disease progression was reported as an event in 68 pts with 38 pts reporting
increased PSA levels. A total of 57 deaths were reported: 9 due to disease
progression; 3 pulmonary embolism; 2 chronic obstructive pulmonary disease; 2
febrile neutropenia; 2 sepsis; 2 septic shock; 12 other causes; and, 25 cause not
specified.
Conclusion: Although subject to the limitations of the post-marketing voluntary
adverse event reporting system, the emerging safety profile of Jevtana is consistent
with that observed in the clinical trial setting.
Disclosure: L. Nicacio: I am an employee of Sanofi and own Sanofi stock. P. Raina:
I am an employee of Sanofi and own Sanofi stock. R. Sands: I am an employee of
Sanofi and own Sanofi stock. S. Neibart: I am an employee of Sanofi and own
Sanofi stock.
949 PARAMETRIC EFFECT SIZE ESTIMATES FROM SIPULEUCEL-T
RANDOMIZED TRIALS
B.A. Blumenstein
Trial Architecture Consulting, Washington, DC, UNITED STATES OF AMERICA
Introduction: Median overall survival (OS) difference is frequently used as a
measure of effect size because it is easily understood. Other effect size estimates can
more fully represent the OS distribution, and are less subject to local variations.
Analysis of the sipuleucel-T D9901 and IMPACT trials using non-parametric
(median) or semi-parametric (hazard ratio [HR]) methods provide 4.5- and
4.1-month estimated median OS differences, respectively, with HRs of 0.586 and
0.752 (not stratified or adjusted). The OS curves from these trials exhibit delayed
separation, suggesting a delayed treatment effect consistent with that shown for
other immunotherapies. In this research, parametric statistical models are used
to account for delayed effect and obtain alternative effect size estimates from D9901
and IMPACT.
Methods: Parametric models based on the Weibull distribution and a modification
of the Weibull distribution that allows for delay of effect were applied. These models
require specification of the general shape of the hazard function.
Results: The table shows the original OS and HR estimates in comparison to those
obtained through parametric modeling. D9901 estimates from the Weibull model
suggested a larger median OS difference vs the original estimates. The OS difference
and the HR estimate using the delayed effect Weibull model were both indicative of
greater sipuleucel-T effect. For IMPACT, the OS difference and HR estimates from
the Weibull model indicated greater effect, but to a lesser degree than in D9901. The
delayed effect modified Weibull model for IMPACT did not support a delayed effect.
Discussion: This statistical modeling illustrates alternative methods of obtaining
effect size estimates that may be particularly applicable to clinical trials of cancer
immunotherapies. For the sipuleucel-T trials, these models suggest a greater
sipuleucel-T effect than obtained from non-parametric or semi-parametric methods.
Study Estimate Type
D9901 Non-parametric/semi-parametric
Weibull Modified Weibull
IMPACT Non-parametric/semi-parametric
Weibull Modified Weibull
NS, delayed effect not supported *Applicable after delayed efffect
Disclosure: All authors have declared no conflicts of interest.
Median
Difference
(mos) Hazard Ratio
4.5 10.3 6.6 0.586 0.585 0.486*
4.1 4.7 NS 0.752 0.749 NS
950 THE EFFECT OF NEUTROPHIL TO LYMPHOCYTE RATIO (NLR)
PRIOR TO TAXOTERE-BASED CHEMOTHERAPY IN PATIENTS
(PT’S) WITH METASTATIC CASTRATION RESISTANT
PROSTATE CANCER (MCRPC)
A. Sella 1 , T. Sella 2 ,S.Kovel 1
1 Oncology, Asaf Harofeh Medical Center, Beer Jacob, ISRAEL, 2 Oncology,
Sheba Medical Center, Ramat Gan, ISRAEL
Introduction: Increasing evidence supports the involvement of systemic
inflammation in cancer development and progression. Neutrophiles/lymphocytes
ration (NLR), a marker of inflammatory response which is associated with poor
outcome in colorectal, gastric, pancreas, hepatocellular, breast, lung and renal cancer
cases. The improved survival with immunotherapy (Provenge) in mCRPC and the
recent report that high NLR in associated with poor outcome in mCRPC treated with
ketoconazole prompted the evaluation of NLR in such pt’s treated with
Taxotere-based chemotherapy.
Methods: During the last decade we treated 62 mCRPC pt’s with Taxotere-based
chemotherapy. Blood counts up to 2 month prior to therapy without infection or
steroid treatment are available in 31 pt’s. Statistical analysis was performed with
SPSS17, survival curve was measured with Kaplan-Meyer curve.
Results: Patient’s characteristics: median age-70 (55-82) years, median PSA-95.2
(1.6-2316), median alkaline phosphatase- 123(10.8-1795)U/ml was elevated (> 115
U/ml) in 18 pt’s (58%) and median hemoglobin-12.1(8.4-15.4) with anemia (< 12 gr/
%) in 15 pt’s (48%). Median survival was 15.8 + 2.2 months (mo.) while PSA
response (> 50% decline) occurred in 14 pt’s (45.1%). Eighteen pts (58%) had NLR >
3.0. The two groups were similar in PSA, alkaline phosphatase elevated levels and
PSA response. We observed no difference in survival nor PFS between the pt’s with
NLR> 3.0 and NLR < 3.0; 17.1 v.s 13.7 mo. and 5.4 v.s 4.5 mo. respectively. Analysis
according to alkaline phosphatase, hemoglobin levels, elevated PSA and alkaline
phosphatase or PSA response was non-significant.
Conclusions: Unlike other cancers, elevated NLR in mCRPC treated with
Taxotere-based chemotherapy does not predict worse outcome.
Disclosure: All authors have declared no conflicts of interest.
951 REPONSE TO CABAZITAXEL IN THE POSTCHEMOTHERAPY
SETTING IN CRPC PATIENTS PREVIOUSLY TREATED WITH
DOCETAXEL AND ABIRATERONE ACETATE
L. Albiges 1 , S. Le Moulec 2 , Y. Loriot 1 , M. Gross Goupil 3 , T. De La Motte Rouge 4 ,
A. Guillot 5 , K. Fizazi 6 , C. Massard 7
1 Medical Oncology, Institut de cancérologie Gustave Roussy, Villejuif, FRANCE,
2 Oncologie Medicale, Hopital du Val de Grace Val de Grace, Paris Cedex,
FRANCE, 3 Medical Oncology, Hôpital Saint-André, CHU bordeaux, Bordeaux,
FRANCE, 4 Medical Oncology, Salpétrière Hospital, Paris, FRANCE, 5 Medical
Oncology, Institut de Cancérologie de la Loire, Saint Priest en Jarez Cedex,
FRANCE, 6 Department of Medical Oncology, Institute Gustave Roussy, Villejuif,
FRANCE, 7 SITEP, Institut de Cancérologie Gustave Roussy, Villejuif Cedex,
FRANCE
Background: Cabazitaxel (a tubulin-binding taxane chemotherapy) and Abiraterone
acetate (AA) have recently been approved for patients with metastatic castration
resistant prostate cancer (CRPC) following docetaxel chemotherapy. Recent studies
suggest that taxane also impact AR signalling such as AA, and could explain
cross-resistance between new hormonal manipulations and taxane chemotherapy.
The aim of this study is to evaluate the antitumor activity of cabazitaxel in patients
whose disease progresses on AA.
Patients and methods: Eligible pts had metastatic CRPC and progression disease
after docetaxel and AA. All the patients received cabazitaxel 20 mg/m2 every 3
weeks + prednisone 5 mg BID. Radiological response by RECIST, PSA response by
PSAWG2 criteria and symptomatic benefit were evaluated.
Results: In the 38 pts treated with cabazitaxel, baseline median age was 69 years
(48-81), ECOG PS 0 or 1 in 90% of pts, and median PSA 350 ng/ml (3,75-9150).
Bone, lymph nodes and visceral metastases were present in 30 pts (90%), 5 pts
(15%), and 5 pts (15%) respectively. An average of 4 cycles of cabazitaxel (range 1-9)
were given, 85% patients received granulocyte-colony stimulating factor prophylaxis
from cycle 1, and 15 pts (39%) continue on cabazitaxel at the time of safety analysis.
Out of 38 patients, 16 patients stopped before completing the full course, 15 of these
patients were due to disease progression. No major toxicities were noticed. Of 32
patients with PSA data available, 18 (56%) pts have had a 50% or greater PSA
decline, 5 pts (15%) have had a partial response.
Conclusion: Cabazitaxel appears active and well tolerated in pts with metastatic
CRPC who are resistant to AA. Our data do not provide any evidence for
cross-resistance between these two agents. Final results will be reported.
Disclosure: All authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds400 | ix313