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1481PD A PHASE II STUDY OF DOVITINIB IN PATIENTS WITH
METASTATIC OR UNRESECTABLE GASTROINTESTINAL
STROMAL TUMORS AFTER FAILURE OF TWO OR MORE
TYROSINE KINASE INHIBITORS
Y. Kang 1 , M.H. Ryu 1 , J.J. Lee 2 , I. Park 1 , J.H. Park 3 , B. Ryoo 1
1 Department of Oncology, Asan Medical Center, University of Ulsan College of
Medicine, Seoul, KOREA, 2 Department of Nuclear Medicine, Asan Medical
Center, University of Ulsan College of Medicine, Seoul, KOREA, 3 Department of
Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine,
Seoul, KOREA
Objectives: This prospective, phase 2 study evaluated the efficacy and safety of
dovitinib in patients (pts) with advanced gastrointestinal stromal tumors (GISTs)
who failed previous standard tyrosine kinase inhibitors (TKI).
Methods: Thirty pts with pathologically proven metastatic or unresectable GIST who
failed a minimum of both imatinib and sunitinib were accrued between Sep 2011
and Apr 2012. Dovitinib was administered orally at 500 mg qd for 5 consecutive days
followed by a 2 day rest period.
Results: The median age was 57.5 years (range, 35-76). All had metastatic disease in
the peritoneum (n = 22), liver (n = 20), lung (n = 4), or bone (n = 4). Thirteen pts
(43%) also failed nilotinib (n = 8), regorafenib (n = 2) or both nilotinib and
regorafenib (n = 3) after failure of imatinib and sunitinib. By RECIST criteria, there
were no objective responses, 19 (63.3%) had stable disease (SD), 5 (16.7%)
progressive disease (PD), and 6 (20.0%) were not evaluable. By EORTC PET criteria
(at 4 weeks), 3 pts (10.0%) achieved a partial response, 15 (50.0%) had SD, 10 (33.3)
showed PD, and 2 were not evaluable. With a median follow-up of 4.8 months
(range, 0.8-7.5), the medi an progression-free survival (PFS) and overall survival were
3.6 months (95% CI, 2.7-4.4) and 6.2 months (95% CI, 4.9-7.5), respectively. PFS
could be predicted by PET response (PD vs no PD) at 4 weeks (p = 0.003). Grade 3
or 4 adverse events of dovitinib with frequency > 5% pts included asthenia (16.7%),
leucopenia (6.7%), thrombocytopenia (6.7%), and hypertension (6.7%). Those
toxicities were manageable with dose modification, and there were no
treatment-related deaths.
Conclusions: Dovitinib showed antitumor activity with manageable toxicities in this
heavily pretreated cohort of GIST patients.
Disclosure: Y. Kang: Honoraria, consultant, and research fund from Novartis. All
other authors have declared no conflicts of interest.
1482PD DASATINIB FIRST-LINE TREATMENT IN
GASTROINTESTINAL STROMAL TUMORS. A MULTICENTER
PHASE II TRIAL OF THE SAKK (SAKK 56/07)
M. Montemurro 1 , J. Domont 2 , P. Rutkowski 3 , A.D. Roth 4 , R. von Moos 5 ,
R. Inauen 6 , D. Dietrich 7 , C. Biaggi 8 , J. Prior 9 , S. Leyvraz 1
1 Centre Pluridisciplinaire d’Oncologie, Centre Hospitalier Universitaire Vaudois -
CHUV, Lausanne, SWITZERLAND, 2 Dept. Medical Oncology, Institut Gustave
Roussy, VILLEJUIF, FRANCE, 3 Department of Soft Tissue/bone Sarcoma and
Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of
Oncology, Warsaw, POLAND, 4 Oncology, University Hospitals of Geneva,
Geneva, SWITZERLAND, 5 Medical Oncology, Kantonal Hospital Graubünden,
Chur, SWITZERLAND, 6 Dept. of Oncology, Kantonsspital St. Gallen, St. Gallen,
SWITZERLAND, 7 Statistics, Swiss Group for Clinical Cancer Research SAKK,
Bern, SWITZERLAND, 8 Trial Coordination, Swiss Group for Clinical Cancer
Research SAKK, Bern, SWITZERLAND, 9 Nuclear Medicine, University Hospital
Lausanne CHUV, Lausanne, SWITZERLAND
Introduction: First line imatinib has improved the outcome of patients (pts) with
gastrointestinal stromal tumor (GIST), but primary and secondary resistance remain
a problem. Dasatinib is a second generation tyrosine kinase inhibitor (TKI) of
bcr-abl, src-family kinases and a number of other oncogenic kinases including kit.
Dasatinib has shown activity against imatinib-resistant cell lines in vitro.
18F-fluorodeoxyglucose positron-emission-tomography (FDG-PET) measures tumor
metabolic activity for early response assessment, which might be of particular use in
the clinical trial setting.
Methods: This two-stage phase II trial investigated dasatinib in patients with
histologically proven, FDG-PET positive, TKI-naïve GIST. Dasatinib starting dose
was 2x70mg/day. Response evaluation was done by serial CT and FDG-PET using
EORTC PET response criteria (Young et al. 1999). PET was reviewed centrally.
Elective surgery was allowed after 6 months of trial treatment. Primary endpoint was
response (CR + PR) by FDG-PET after one month of dasatinib.
Results: 47 of planned 52 pts have been enrolled from December 2007 to November
2011, when the trial was terminated due to slow accrual. 43 pts were eligible. Median
age was 61 years, 24 pts were male, 19 female. 30 pts had a performance status of 0
and thirteen of 1. Mutational data are available for 28 pts so far. 20 had a KIT exon
11, one a KIT exon 9 mutation, and 7 were wild-type. At a median follow-up of 12.4
Annals of Oncology
months, 15 pts were still on treatment. Pts went off trial for elective surgery (n = 6),
progression (n = 13), toxicity (n = 4), other reasons (n = 2) and three patients died.
5% of pts experienced G4, and 38% of pts G3 toxicity, which were most often
gastrointestinal or pulmonary. 28 pts had their dose reduced or interrupted. The
primary endpoint, FDG-PET response rate (CR + PR) at 4 weeks was 72% (14 CR, 17
PR, 7 SD, 3 PD, 2 not evaluable). The response rate in patients with a KIT Exon 11
mutation was 80%, in wild-type patients 57%. Median progression-free survival is
11.1 months and median overall survival not yet reached.
Conclusions: Dasatinib shows promising efficacy in TKI-naïve pts with FDG-PET
positive GIST.
Disclosure: M. Montemurro: Speakers fees and travel grants - Bayer, Pfizer, Novartis.
P. Rutkowski: Consultant - BMS, Novartis, MSD Speakers fees and travel grants -
Novartis, Pfizer, MSD, BMS, Roche. R. von Moos: Consultant/Advisor - AMGEN,
Novartis, Roche, BMS, Pfizer, Merck Speakers fees - Roche, Amgen institutional
Research Funds - AMGEN Expert Testimony - AMGEN. All other authors have
declared no conflicts of interest.
1483PD INNO-206 IS AN ACTIVE DRUG FOR RELAPSED ADVANCED
SOFT TISSUE SARCOMA
S. Chawla 1 , V.S. Chua 1 , A. Hendifar 1 , D. Quon 1 , S. Negre 1 , K.N. Ganjoo 2 ,
K. Sankhala 3 , Y. Lavinski 4 , S. Wieland 5 , D. Levitt 5
1 Clinical Research, Sarcoma Oncology Center, Los Angeles, CA, UNITED
STATES OF AMERICA, 2 Medical Oncology, Stanford University Medical School,
Palo Alto, CA, UNITED STATES OF AMERICA, 3 Medical Oncology, University of
Texas Health Science Center, San Antonio, TX, UNITED STATES OF AMERICA,
4 Research, MutualHealth LLC, Newport Beach, CA, UNITED STATES OF
AMERICA, 5 Clinical Development, CytRx Corporation, Los Angeles, CA, UNITED
STATES OF AMERICA
Background: We have studied the safety and tumor response of a doxorubicin
conjugate, INNO-206, in patients with metastatic STS who progressed on prior
chemotherapy. INNO-206 is a conjugate of doxorubicin attached to an acid-sensitive
linker that binds covalently to cysteine-34 in circulating albumin.
Methods: INNO-206 was administered IV at 350 mg/m 2 (260 mg/m 2 dox. eq.) every
21 days for up to 8 consecutive cycles. Tumor response was monitored every other
month and treatment continued until tumor progression or unacceptable toxicity.
Standard safety monitoring was performed and cardiac function was followed
periodically using MUGA or cardiac ultrasound.
Results: As of May 1, 2012, 19 patients were entered in the study. 13/19 patients had
STS of various types. Of the initial 19 patients treated at the 350 mg/m 2 dose, no
individuals experienced a grade 3 or 4 non-hematological toxicity during Cycle
1. The majority of patients demonstrated transient grade 3 or 4 neutropenias that
resolved prior to the next cycle with and without G-CSF treatment. No patient
exhibited relevant cardiotoxicity as determined by MUGA or cardiac ultrasound. Of
19 patients, serious adverse events included febrile neutropenia (3) sepsis (1) and
mucositis (1). Of the 13 patients with STS, 5 objective partial responses (3 of whom
received prior doxorubicin) are ongoing as well as 7 patients with stable disease
(median 6.43 months, range 1-10.7+ months). 1/13 patients had progressive disease
at the first evaluation. 2/19 patients died with the first cycle (1 PD, 1 sepsis).
Conclusion: INNO-206 is an active drug for the treatment of patients with advanced
STS who have failed prior chemotherapy. Cumulative doses of 2000 mg/m 2 of
doxorubicin equivalents have been achieved, which is over 3½ x the peak cumulative
dose of standard doxorubicin. Adverse events are primarily hematological and no
cardiotoxicity has been observed.
Disclosure: S. Chawla: Corporate sponsored research from CytRx Corporation.
S. Wieland: Salary and stock ownership from CytRx Corporation. D. Levitt:
Salaryand stockownership from CytRx Corporation. All other authors have declared
no conflicts of interest.
1484PD SELECTIVE INTERNAL RADIATION THERAPY (SIRT) FOR
GIST LIVER METASTASES RESISTANT TO TYROSINE
KINASE INHIBITORS
P. Hohenberger 1 , N. Rathmann 2 , A. Peschel 2 , J. Schuette 3 , S.O. Schoenberg 2 ,
D. Dinter 2 , S. Diehl 2
1 Dept. of Surgery, UniversitaetsMedizin Mannheim, Mannheim, GERMANY,
2 Dept. of Radiology and Nuclear Medicine, UniversitätsMedizin Mannheim,
Mannheim, GERMANY, 3 Department of Oncology and Hematology,
Schwerpunktpraxis Haematoonkologie Duesseldorf, Duesseldorf, GERMANY
Background and aim: The liver is the typical location of metastases from
gastrointestinal stromal tumors (GIST). Usually, metastases of GIST are treated by
tyrosine kinase inhibitors (imatinib, sunitinib or others). In patients with multiple
metastases resistant to drugs and not amenable to surgical resection interventional
ix480 | Abstracts Volume 23 | Supplement 9 | September 2012