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Patients and methods: From August 2005 to June 2009 we enrolled patients (pts)
with histologically proven diagnosis of DSRCT, refractory to conventional treatment.
Inclusion criteria comprised immunohistochemical positivity of imatinib targets
(PDGF-Rα and β). Treatment consisted of imatinib 400 mg p.o. daily. Primary
endpoint of the study was objective response rate. Secondary endpoint was safety and
tolerability assessment.
Results: Of the 13 enrolled patients, 8 pts were evaluable for response (4 screening
failure and 1 never treated). Median age was 20 years (range, 9-32). M/F ratio was 7/
1. ECOG PS was 0 in 6 pts. Median time from diagnosis was 24.5 months (range,
6-148). 75% of pts had metastatic disease. The primary site was abdominal-pelvic for
all pts. PDGFRα and β were expressed with an heterogeneous intensity pattern.
Objective responses at first radiological evaluation at 3 months were: stable disease in
one pt (12.5%) and progressive disease in 7 (87.5%) pts. Treatment-related adverse
events were G1-2 nausea/vomiting, fatigue and periorbital oedema.
Conclusions: In our limited case series, imatinib showed no efficacy in the treatment
of DSRCT pts unresponsive to conventional therapy, despite molecular-based
selection of pts. Probably to identify responder pts, it is necessary a more complex
evaluation comprehensive of both levels of expression and activation of PDGFRα and
β. Furthermore, enrolled pts were affected by advanced refractory disease, probably
less responsive to target therapies. It would be hopeful a global effort to define a new
combined approach based on the association of conventional chemotherapy and
biological drugs.
Disclosure: C. Gnocchi: Novartis Patient Advocacy Manager. All other authors have
declared no conflicts of interest.
1495P SUNITINIB THERAPY IN ADVANCED ALVEOLAR SOFT PART
SARCOMAS
H.M. Kosela, K. Wiater, T. Switaj, A. Klimczak, S. Falkowski, P. Rutkowski
Soft Tissue/bone Sarcoma and Melanoma, MSC Memorial Cancer Centre and
Institute Maria Sklodowska-Curie, Warsaw, POLAND
Background: Alveolar soft part sarcoma (ASPS) is a rare entity making up < 1% of
soft tissue sarcomas (STS). It is characterized by slow, indolent growth but with a
high frequency of metastatic disease especially to lungs. Chemotherapeutic regimens
used for the treatment of other soft tissue sarcomas lack efficacy in ASPS. The
purpose of our analysis was to assess sunitinib activity in ASPS.
Methods: Since July 2009, 7 patients with metastatic ASPS have been treated with
sunitinib continuous daily dosing 37,5mg (1 pts started treatment at 50mg/d on a 4/2
week schedule). All patients’ initial performance status according to ECOG was 0-1.
Median age at time of diagnosis was 23 yrs (range 18-57), gender distribution M/F was 1/
6. Primary localization of the tumor was: lower extremity (3), trunk (2), retroperitoneum
(1), pelvis (1). Primary tumor size ranged from 5 to 12 cm (median 7cm). All patient had
unresectable metastases to the lungs. 57% of thepatientswerepreviouslytreatedwith
standard chemotherapy. Median time from diagnosis to start of sunitinib therapy was 6
months (range: 2-156). Responses were evaluated after 2 months from baseline, then
every 3 months by CT scan and/or MRI, according to RECIST criteria.
Results: At the time of present analysis 3 of the patient continue therapy. After 2
months of treatment 2 patients had RECIST PR, 5 SD. Median PFS was 15 months
with 86% patients free of progression of the disease at 6 months. Median therapy
duration was 18 months (range: 5-31). Median OS was 15 months; 3 patients died due
to disease progression at the time of analysis. One of the patients had SD after 4
months of treatment, interrupted treatment for 3 months and experienced progression
of the disease, after restarting therapy she again gained SD lasting 12 months. Toxicity
was rather moderate. All the patients experienced some side effects, 4 patients (57%)
had toxicity grade 3/4 CTC. The common treatment toxicity was neutropenia,
hypothyroidism, arterial hypertension, hand and foot syndrome. 2 patients required
dose reduction. There was one death related to the treatment (sepsis).
Conclusion: Our analysis shows efficacy of sunitinib in patients with advanced ASPS.
Disclosure: P. Rutkowski: honoraria: Pfizer and Novartis. All other authors have
declared no conflicts of interest.
1496P SUNITINIB MALATE IN CLEAR CELL SARCOMA
S. Stacchiotti 1 , E. Palassini 1 , T. Negri 2 , C. Morosi 3 , A. Messina 3 , R. Patuzzo 4 ,
A. Gronchi 4 , S. Pilotti 2 , P.G. Casali 1
1 Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan,
ITALY, 2 Pathology and Molecular Biology, Fondazione IRCCS Istituto Nazionale
dei Tumori, Milan, ITALY, 3 Radiology, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, ITALY, 4 Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori,
Milan, ITALY
Background: Clear cell sarcoma (CCS) is a rare soft tissue sarcoma, characterized in
most cases by the t(12;22), resulting in the EWS-ATFE1 fusion protein. It has a high
Annals of Oncology
metastatic potential. CCS is poorly sensitive to chemotherapy. We already reported
on the activity of sunitinib (SM) in one case of CCS.
Methods: Since September 2009, 9 patients with progressive, metastatic CCS (M/
F 3/6; median age 36 yrs; translocated/ non translocated: 6/3; site of primary:
extremities 6, other 3; pretreated: 9) have been treated with continuous SM 37.5
mg/day, on a named basis. PET response was assessed in 6 cases. Responses
were evaluated after 2 months from baseline, then every 3 months by CT scan
and/or MRI, according to RECIST. Pre-treatment PDGFRB and VEGFR status
analysis by immunohistochemistry, western/blotting and phospho-RTK array is
ongoing in evaluable cases.
Results: At the time of the present analysis, 6/9 pts are evaluable for response (1
early interruption; 2 just started), and 4 patients are still on treatment. After 3
months of SM, 3 patient had a RECIST partial response (PR) (50%), along with
subjective improvement in symptoms, 1 stable disease (SD), 2 progressive disease
(PD). PET was consistent. One patient had a complicated major response
characterized by an ulcer to the site of previous surgery; thus she underwent surgery
with evidence of pathologic partial response, marked by extensive necrosis. The
median PFS is 5 months (range 2-7).
Conclusions: SM is active in a proportion of CCS. Prospective studies are needed.
Disclosure: S. Stacchiotti: Pfizer: reseach grant for studies in which my Institution is
involved; honoraria. E. Palassini: Pfizer: research grant for studies in which my
Institution is involved. P.G. Casali: Pfizer: research funds for studies in which my
Institution is involved; Compensated Advisory; Honoraria. All other authors have
declared no conflicts of interest.
1497P SIMULTANEOUS TARGETING OF THE INSULIN-LIKE
GROWTH FACTOR 1 RECEPTOR (IGF-1R) AND ANAPLASTIC
LYMPHOMA KINASE (ALK) IN EMBRYONAL AND ALVEOLAR
RHABDOMYOSARCOMA
J.C. van Gaal 1 , Y.M.H. Versleijen-Jonkers 1 , M.H.S. Roeffen 1 , U.E. Flucke 1 ,
G. van der Heijden 1 , A.J.H. Suurmeijer 2 , E.S.J.M. De Bont 3 , W.T.A. van der
Graaf 4
1 Department of Medical Oncology, Radboud University Nijmegen Medical
Centre, Nijmegen, NETHERLANDS, 2 Pathology, University Medical Center
Groningen, Groningen, NETHERLANDS, 3 Pediatric Oncology, University Medical
Center Groningen, Groningen, NETHERLANDS, 4 Medical Oncology /452,
Radboud University Medical Centre MijmegenUniversity Medical Center
St. Radboud, Nijmegen, NETHERLANDS
Introduction: Rhabdomyosarcoma (RMS) is an aggressive soft tissue tumour that
occurs predominantly in children and adolescents. Its two most common forms
are embryonal (eRMS) and alveolar RMS (aRMS). Although survival has increased
over the past decades after the introduction of multi-agent chemotherapy, the
survival for the high-risk subpopulation remains poor (not exceeding 50%).
Therefore, there is an urgent need for new systemic treatment options. The aim of
the current study is to investigate the insulin-like growth factor-1 receptor
(IGF-1R) and anaplastic lymphoma kinase (ALK) pathway as potential targets in
RMS.
Methods: A total of 112 paraffin-embedded RMS tumor specimens (eRMS n = 86;
aRMS n = 26) were collected on a tissue microarray. IGF-1R and ALK expression was
evaluated by immunohistochemistry. A binary scoring system was used in which
staining was scored positive when present in at least 10% of the tumour cells. The
effect of the ALK small molecule inhibitor NVP-TAE684 (Novartis), the IGF-1R
monoclonal antibody R1507 (Roche) and combined treatment was investigated by
cytotoxicity assay MTT in four RMS cell lines (aRMS Rh30 and Rh41; eRMS Rh18
and RD).
Results: Expression of IGF-1R was seen in 72% of aRMS and 62% of eRMS,
respectively. ALK expression was observed in 92% of aRMS and 39% of eRMS.
Co-expression of IGF-1R and ALK was observed in 68% of aRMS and 32% of eRMS.
In vitro, inhibition of the IGF-1R by R1507 resulted in diminished cell growth only
in aRMS cell line Rh41 (IC50 11 ng/ml). NVP-TAE-684 resulted in diminished cell
growth in aRMS cell lines Rh41 (IC50 103 nM) and Rh30 (IC50 211 nM), and to a
lesser extent in eRMS cell lines Rh18 (IC50 585 nM) and RD (IC50 734nM).
Simultaneous treatment could be assessed in aRMS cell line Rh41 by using different
concentrations of R1507 and NVP-TAE684, and revealed a synergistic effect
(combination index