Download the ESMO 2012 Abstract Book - Oxford Journals

Annals of Oncology
664TiP A PHASE I TRIAL OF IRINOTECAN (IRI) AND BKM120 IN
PREVIOUSLY TREATED PATIENTS (PTS) WITH METASTIC
COLORECTAL CANCER (MCRC)
J.C. Baranda 1 , G. Reed 2 , S. Williamson 1 , E. Dickman 1 , M. Stoltz 1 , R. Madan 3 ,
L. Wright 1 , K. Bhalla 1 , A. Godwin 3
1 Hematology and Medical Oncology, University of Kansas Cancer Center,
Westwood, KS, UNITED STATES OF AMERICA, 2 Pharmacology. Toxicology and
Therapeutics, University of Kansas Medical Center, Kansas City, KS, UNITED
STATES OF AMERICA, 3 Pathology and Laboratory Medicine, University of
Kansas Medical Center, Kansas City, KS, UNITED STATES OF AMERICA
Background: Reversal of Iri resistance may result with use of Iri plus anti-EGFR
antibody in pts with kras wild-type mCRC. BKM120 is an oral pan-class PI3K
inhibitor. The published results of a phase I trial of single agent BKM120 showed
that BKM120 was well-tolerated and safe with favorable PK profile and promising
anti-tumor effect.
Methods: The primary objective of this phase I trial is to identify the maximum
tolerated dose (MTD) for Iri and BKM120 combination in previously treated
mCRC. The secondary objectives are to characterize the PK of Iri with or
without BKM120 as well as PK of BKM120 when administered with Iri, to
determine clinical response to the combination, and to correlate the expression
of biomarkers associated with PI3K signaling pathway with clinical response to
the combination of Iri plus BKM120. A traditional 3 + 3 dosing scheme is used
for dose escalation. Iri is given intravenously every 14 days and BKM daily. Iri
starts on cycle 1 day 1 while BKM120 starts after 24 hours after the first dose
of Iri to allow us to monitor the PK of Iri both in the absence and presence of
BKM120. The patients are assessed for safety and toxicities every cycle (q14
days).
Results: Eleven pts have been enrolled: six were evaluable for toxicity: 3 in
cohort 0 (Iri 120 mg/m 2 + BKM120 50 mg/d) and 3 in cohort 1 (Iri 150 mg/m 2
+ BKM 120 50 mg/d). The most common drug related adverse events were
nausea and vomiting, diarrhea, fatigue, hyperglycemia, and elevation of
transaminases. One dose limiting toxicity (DLT), genital mucositis, was observed
in a male pt in Cohort 1. This resolved in less than 7 days but pt missed more
than 7 days of BKM120. The MTD has not been reached. Of the 4 pts who
have completed 4 cycles of therapy 3 had stable disease and one had progressive
disease. The cycle 1 vs cycle 2 PK for cohort 0 showed SN-38 mean Cmax2/
Cmax1 was 0.89 + 0.16 and mean AUC2/AUC1 1.07 + 0.16. The Iri PKs for
subsequent cohorts and BKM120 PKs as well as the molecular correlates will be
presented.
Conclusion: This is the first human trial of the combination of Iri and BKM120. No
significant toxicities have been observed and the PK of Iri does not seem to be
affected by BKM120. These preliminary data support continuing the effort to find
the MTD for the combination of Iri and BKM120 for use in phase II trials and to
identify potential biomarkers of response and toxicities.
Disclosure: J.C. Baranda: Research Funds: Novartis, Roche. K. Bhalla: Novartis,
Research Funding Novartis, honorarium, advisor. All other authors have declared no
conflicts of interest.
665TiP USE OF PANITUMUMAB IN PATIENTS WITH RECURRENT
OR PROGRESSIVE COLORECTAL CANCER - AN INTERIM
ANALYSIS OF THE VECTIS STUDY
R. Lakomy 1 , W. Rogowski 2 , B. Pikó 3 , C. András 4 , E. Molnar 5
1 Department of Clinical Oncology, Masaryk Memorial Cancer Institute, Brno,
CZECH REPUBLIC, 2 Department of Oncology, ZOZ MSWiA z Warminsko
Mazurskim Centrum Onkologii, Olsztyn, POLAND, 3 Dep. of Clinical Oncology,
3Pándy Kálmán County Hospital, Center of Oncology, Gyula, Gyula, HUNGARY,
4 Dpt. of Clinical Oncology, 4Medical University, Dpt. of Oncology, Debrecen,
Debrecen, HUNGARY, 5 Medical, Amgen, Budapest, HUNGARY
Registry Number: 20080618
Background: Panitumumab (Pmab; Vectibix®) is a fully human monoclonal antibody,
which binds specifically to the human epidermal growth factor receptor (EGFr). Skin
toxicity (ST), a pharmacological effect observed with EGFr inhibitors, appears in
almost all patients (pts) treated with Pmab and is usually mild to moderate in severity.
The VECTIS study was designed to determine the safety and efficacy of Pmab as
monotherapy in daily practice with special reference to ST and its management.
Methods: This is an open-label, prospective, non-interventional study collecting data
from pts from CEE countries, aged ≥18 years, who have EGFr expressing mCRC
with wild type KRAS gene tumour status receiving Pmab monotherapy (6 mg/kg
Q2W) after failure of chemotherapy regimens containing 5-FU, oxaliplatin and
irinotecan. This interim analysis includes the data collected between 12/2008 and 06/
2011 from pts in Hungary, Poland, and the CzechRepublic. The observation period
was limited to 18 cycles.
Results: At the time of reporting, 177/205 (86.3%) enrolled pts have experienced a
total of 266 ST events with an incidence rate (IR) (events per pt per year) of 3.47
(95% confidence interval [CI] = 3.07, 3.91); 15 pts experienced Grade 3 ST with an
IR of 0.20 (95% CI = 0.11, 0.32) and no pts had ST Grade ≥4. Of the recorded ST
events, 25.9% have resolved; 3.4% have resolved with consequences; 19.9% continue
but are improving; and 50.8% have not resolved. Overall, 69.8% of pts required
therapeutic measures for ST. Four serious Adverse Drug Reactions (ADRs) were
reported. Of 6 deaths that occurred, none was related to Pmab. Four pts have
stopped Pmab therapy due to ADRs including ST or other toxicity.
Overall
(N = 205) % (95% CI)
ST Grade ≥ 2
(N = 112) % (95% CI)
Tumor response 26.8 (20.9, 33.4) 30.4 (22.0, 39.8)
Disease control rate 67.8 (60.9, 74.1) 70.5 (61.2, 78.8)
Free from progression (18 cycles) 12.7 (8.5, 18.0) 13.4 (7.7, 21.1)
A statistically significant positive correlation was observed between severity of ST and
the best response (r = 0.13) as well as tumor response (r = 0.15).
Conclusion: In clinical practice, Pmab monotherapy appears to be well tolerated and
effective in pts who have heavily pre-treated mCRC with wild-type KRAS status. This
study is sponsored by Amgen GmbH CEE Headquarters.
Disclosure: R. Lakomy: Vectis study. W. Rogowski: Vectis study, Pegfilgrastim study.
B. Pikó: Vectis study, Pegfilgrastim study. C. András: Vectis study, Pegfilgrastim
study, Amgen sponsored scientific event speaker. E. Molnar: employment possition
Amgen, stock
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds397 | ix223