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may have led to reduced dose and shortened duration of treatment and how costs of
care and patient outcomes might be affected.
Disclosure: Y. Su: Employment and Leadership Role: Bristol-Myers Squibb
(employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb
(myself). P. Landsman-Blumberg: Stock Ownership: Merck & Co., Inc. (myself).
C. Poehlein: Employment and Leadership Role: Bristol-Myers Squibb (employment,
myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself). I. Waxman:
Employment and Leadership Role: Bristol-Myers Squibb (employment, myself,
compensated). Stock Ownership: Bristol-Myers Squibb (myself). All other authors
have declared no conflicts of interest.
811P CLINIC AND HOME BLOOD PRESSURE MEASUREMENTS
ARE RELIABLE FOR GUIDING THERAPY IN PATIENTS WITH
METASTATIC RENAL CELL CARCINOMA RECEIVING
AXITINIB AS FIRST-LINE THERAPY
V. Grünwald 1 , M.N. Fishman 2 , M. Carducci 3 , A. Bair 4 , Y. Chen 4 , S. Kim 4 ,
B.I. Rini 5
1 Clinic for Hematology, Hemostasis, Oncology, Hannover Medical School,
Hannover, GERMANY, 2 Genitourinary Program, H. Lee Moffitt Cancer
CenterUniversity of South Florida, Tampa, FL, UNITED STATES OF AMERICA,
3 Kimmel Cancer Center, Kimmel Cancer Center, Baltimore, MD, UNITED
STATES OF AMERICA, 4 Pfizer Oncology, Pfizer Oncology, San Diego, CA,
UNITED STATES OF AMERICA, 5 Cleveland Clinic Taussig Cancer Institute,
Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, UNITED STATES OF
AMERICA
Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth
factor receptors 1, 2, and 3, is approved in the US in patients (pts) with metastatic renal
cell carcinoma (mRCC) who failed 1 prior systemic therapy. Blood pressure (BP)
increases are commonly observed with axitinib. BP measurements are subject to error and
can vary by method employed, eg, home measurements by pts, ambulatory monitoring,
and in-clinic assessments. As part of a phase II study evaluating safety and efficacy of
axitinib for treatment-naïve mRCC, we prospectively characterised and compared BP
measurements from clinic, home, and 24-hr ambulatory BP monitoring (ABPM).
Methods: Clinic BP was obtained at baseline, Days 1 and 15 of the first 2 treatment
cycles, and Day 1 of subsequent 28-day cycles. Home BP was obtained by pts twice
daily during the treatment period. In a subset of pts, 24-hr ABPM was performed at
baseline and Days 4 and 15.
Results: 213 pts enrolled. Mean age was 61 years; 67% were men. Pooled median
progression-free survival was 14.5 months. No pts had uncontrolled hypertension
(HTN) at study entry. All-grade HTN occurred in 63% and grade 3 in 29%, with no
grade 4 HTN. By 24-hr ABPM, median increases from baseline in systolic BP/
diastolic BP (sBP/dBP) were 10/8 mmHg by Day 4, with modest incremental
increases by Day 15 and stabilisation thereafter; changes in BP were generally
consistent at all clock times of day. dBP outcomes were highly consistent between
clinic and home measurements (mean 83 ± 9 vs 83 ± 9 mmHg on Cycle 1 Day 15,
n = 200; 84 ± 11 vs 84 ± 10 mmHg on Cycle 3 Day 1, n = 171). Similarly, dBP
measurements were consistent between clinic and 24-hr ABPM (mean 84 ± 10 vs 84
± 9 mmHg on Cycle 1 Day 15, n = 63). Consistent sBP outcomes were also observed
across various time points and measurement modalities.
Conclusions: BP increased early with axitinib and was generally well-managed. 24-hr
ABPM suggests there is no best time of day to measure BP; rather, measuring at a
consistent time of day in individual pts would provide the most useful data. Results
from clinic and home monitoring appear consistent and both could be reliable in
measuring BP and guiding axitinib therapy.
Disclosure: V. Grünwald: Advisory and honoraria: GSK, Pfizer, Roche, Novartis,
Bayer. Research grant: Pfizer. M.N. Fishman: Dr Fishman has received research
funding, participated in compensated advisory board and promotional presentations
from the manufacturer of the study drug. M. Carducci: Pfizer DSMB for unrelated
product (compensated). JHU received research funding for conduct of the trial. A.
Bair: Employee of and own stock in Pfizer. Y. Chen: Employee of and own stock in
Pfizer. S. Kim: Employee of and own stock in Pfizer. B.I. Rini: Consulting and
research funding from Pfizer.
812P ROLE OF GENETIC VARIANTS IN THE PI3K/AKT/MTOR
PATHWAY IN RENAL CELL CARCINOMA PATIENTS TREATED
WITH EVEROLIMUS- A PILOT STUDY
L. Bodnar 1 , R. Stec 1 , M. Cichowicz 2 , S. Cierniak 3 , M. Smoter 4 ,W.Kozłowski 2 ,
C. Szczylik 1
1 Department of Oncology, Military Institute of Medicine, Warsaw, POLAND,
2 Department of Pathology, Military Institute of Medicine, Warsaw, POLAND,
3 Pathology, Military Institute of Medicine, Warsaw, POLAND, 4 Oncology, Military
Institute of Medicine, Warsaw, POLAND
Background: The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway is
involved in growth regulation, proliferation control and metabolism in renal cell
Annals of Oncology
carcinoma (RCC). In our prospective pilot study, we determined whether common
genetic variations in the AKT/ PI3K, FRAP1 (encoding mTOR) are associated with
clinical outcomes in RCC patients who underwent palliative therapy with everolimus.
Patients and methods: Our pilot study was designed to assess everolimus efficacy in
RCC patients relapsed after TKI inhibitors (sunitinib and/or sorafenib). Patients were
treated with everolimus 10 mg daily orally until disease progression. The genomic
DNA was extracted from formalin-fixed, paraffin-embedded primary tumor RCC
tissues. 12 potentially functional SNPs in 4 key genes (AKT1, AKT2, FRAP1,
PIK3CA) were determined using a real-time PCR genotyping assay and analyzed for
association with response to therapy, progression free survival (PFS) and overall
survival (OS).
Results: Median age of 45 enrolled patients was 62 years (range, 41–78). At a median
follow-up duration of 8,6 months, the 6-month PFS rate was 53.3%. Partial response
was observed in 4,4% (2/45) of the patients. Median PFS was significantly prolonged
in the PIK3CA rs6443624 for the CC genotype in comparison to the AA/AC
genotype (8.9 months versus 5.5 months, log rank, p= 0.0157). In the multivariate
analysis elevated corrected serum calcium and PIK3CA rs6443624 for the AA/AC
genotype were unfavorable predictors of PFS (HR 5.25; 95% CI, 1.75–15.75 and HR
3.48; 95%CI, 1.47–8.25, respectively, p < 0.05). 1-year OS rate for patients with
PIK3CA rs6443624 CC and AA/AC genotype was 86% and 51%, respectively (p =
0.0018). In multivariate analysis PIK3CA rs6443624 for the AA/AC genotype and
elevated LDH serum level remained significant for OS (HR 18.7; 95% CI,2.70–129.38
and HR 9.7; 95% CI,2.18 – 43.07, respectively; p < 0.05).
Conclusion: These results suggest that PIK3CA rs6443624 genetic variation in PI3K/
AKT/mTOR pathway may modulate clinical outcomes in patients with RCC who
undergo chemotherapy with everolimus. Further clinical studies are needed to
confirm these findings.
Disclosure: All authors have declared no conflicts of interest.
813P THE NOVEL CANCER VACCINE, CONSISTING OF
GENETICALLY MODIFIED ALLOGENEIC TUMOR CELLS AND
IMMUNOMODULATOR MGN1601: UPDATED RESULTS OF A
PHASE 1-2 STUDY IN PATIENTS WITH ADVANCED RENAL
CELL CARCINOMA
I.G. Schmidt-Wolf 1 , S. Hauser 2 , S. Weikert 3 , V. Grünwald 4 , M. Schroff 5 ,
M. Schmidt 6 , E. Weith 6 , M. Tschaika 6 , B. Wittig 7
1 Department of Medicine III, Center for Integrated Oncology, University of Bonn,
Bonn, GERMANY, 2 Department of Urology, University of Bonn, Bonn,
GERMANY, 3 Clinic for Urology, Charite, Berlin, GERMANY, 4 Clinic for
Hematology, Hemostaseology, Oncology, Hannover Medical School, Hannover,
GERMANY, 5 Board, Mologen AG, Berlin, GERMANY, 6 Clinical Development,
Mologen AG, Berlin, GERMANY, 7 6Foundation Institute Molecular Biology and
Bioinformatics, Freie Universität Berlin, Berlin, GERMANY
Background: MGN1601 consists of two active pharmaceutical ingredients: genetically
modified allogeneic tumor cells expressing IL-7, GM-CSF, CD80 and CD154 and a
TLR9 agonist, synthetic DNA-based immunomodulator dSLIM®. The first-in-man
phase 1–2 clinical trial (ASET trial) has been conducted in patients with advanced
renal cell carcinoma failed previous therapy lines and without further available
standard therapy.
Methods: The ASET study is a multicentric, open, single-arm phase 1-2 clinical
study and consists of the treatment, extension and follow up phases. The safety,
efficacy and immunogenicity parameters were evaluated based on clinical and
laboratory assessments, monitoring of patients’ quality of life (QoL) with QLQ-C30,
immunological tests, and central radiological investigations according to RECIST 1.1
as well as immune related Response Criteria.
Results: Ten of nineteen study patients completed the treatment per protocol (TPP).
Two patients with disease control after 12-weeks continued treatment in the
extension phase. One of them is still under therapy showing tumor remission since
48 weeks. The second patient developed radiological PD after 60 weeks of treatment.
Seven patients from the TPP population are still alive with stable disease for up to 65
weeks. Evaluation of the QoL showed that patients of the TPP group have improved
median symptom score from 45.8 to 58.3 in course of treatment. Drug-related AE
included mild fever, edema, exanthema, pruritus, intermittent arthralgia, fatigue, and
moderate soft tissue infection. Local reactions on injection site consisted mostly of
redness up to 50 mm, which were available up to 7 days. The local reactions have no
negative impact on the quality of life and daily activities of the patients. Six of ten
TPP patients showed significant improvement in the immune status in lymphocyte
transformation test.
Conclusions: The allogeneic tumor cell-based cancer vaccine MGN1601 shows
promising efficacy and a favourable safety profile in the late stage mRCC patients. A
phase 2 clinical study in mRCC patients with MGN1601 as third-line therapy is
under development.
Disclosure: M. Schroff: Board member of Mologen. M. Schmidt: Mologen employee.
E. Weith: Mologen empoyee. M. Tschaika: Mologen employee. B. Wittig: Member of
Scientific Advisory Board of Mologen. All other authors have declared no conflicts of
interest.
ix268 | Abstracts Volume 23 | Supplement 9 | September 2012