Annual Meeting Proceedings Part 1 - American Society of Clinical ...

654s Sarcoma
10096 General Poster Session (Board #54A), Sun, 8:00 AM-12:00 PM
Analysis of the quality of reporting surgical procedures in patients undergoing
resection for primary gastrointestinal stromal tumors: A reporting tool
derived from the EORTC–STBSG 62024 trial. Presenting Author: Peter
Hohenberger, Universitätsklinikum Mannheim, Mannheim, Germany
Background: Features of surgery for the primary tumor (rupture, extent and
completeness of resection) contribute significantly on the indication for
adjuvant treatment in patients with GIST. No reporting tool for surgery for a
primary GIST has been established. EORTC 62024 is a phase III trial
evaluating the use of adjuvant imatinib in GIST and was used for an
analysis of the data of surgical procedures. Methods: 908 pts. from 11
countries were recruited. At study entry, a copy of the surgical record and
pathology report had to be submitted in addition to the case record forms
(CRFs) which included a surgical questionnaire on 19 items on the
circumstances of the resection (elective/emergency, GIST diagnosis established
preop., tumor rupture, R-status, concordance of preop. and intraop.
staging, surgical technique, complications). We then reviewed the original
documents and compared them with the documentation on the CRFs. The
full set of data was available from 793/906 patients (87.3%). Results: The
diagnosis of GIST was known preop. in 58% of the cases, and 12% of the
pts. had been treated as an emergency. The R0 resection rate was 87%.
The incidence of tumor rupture was 9% and 24% of the pts. had undergone
lymphadenectomy. The consistency between pre- and intraoperative findings
was 82%. The concordance between CRFs and original documents
was 77%. Concordance of the original documents with the surgical
questionnaire (CRFs) was critical in 4/19 items. Discrepancies and
misinterpretation rates were highest when data managers from medical
oncologists had completed the CRFs based on letters of patient discharge.
Based on the evaluation, the surgical reporting tool can be refined and
shortened to 13 items for future applications. Conclusions: Findings at
surgery for the primary tumor not properly reported might significantly
influence the decision of whether or not to treat patients with adjuvant
imatinib. The refined surgical reporting tool could be helpful to gather all
relevant information about the intraoperative elements of surgery for the
primary GIST. Surgeons are to be asked to report those data themselves.
10098 General Poster Session (Board #54C), Sun, 8:00 AM-12:00 PM
Doxorubicin, cisplatin, and ifosfamide (API) as first-line therapy for
relapsed or metastatic uterine leiomyosarcoma. Presenting Author: Julien
Hadoux, Institut Gustave Roussy, Villejuif, France
Background: Uterine leiomyosarcomas (ULMS) are rare gynecologic malignancies
characterized by a poor prognosis due to a high rate of local and
metastatic recurrences. Chemotherapy (CT) with doxorubicin or ifosfamide
or both is associated with a 10 to 30% objective response rate (ORR) and a
cisplatin-based multiCT approach achieved a good response rate (DECAV
therapy: API � dacarbazine � vindesine, 54% ORR in uterine sarcomas),
though toxic. We aimed to determine efficacy and toxicity of doxorubicin,
cisplatin and ifosfamide (API) combination as first line treatment of
metastatic or relapsed ULMS (MRULMS). Methods: This monocentric study
included MRULMS pts with a physiological age � 65 y. CT consisted in
doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/d d1d2 � mesna, cisplatin 75
mg/m² d3, � G-CSF; q 3 weeks. Results: Results in 38 pts with MRULMS
were analyzed; median age was 51 (40-64), median cycles of CT was 5; 8
(21%) pts were treated for local relapse, 21 (55.3%) for metastatic disease
and 9 (23.7%) for both. Metastatic sites were: lungs in 16 pts (42.1%),
pelvis in 7 pts (18.4%), liver in 7 pts (18.4%), peritoneum in 6 pts
(15.8%) and bone in 5 pts (13.2%); 14 pts (36.8%) had a multisite
metastatic disease. Main grade 3-4 toxicities in 38 pts were neutropenia
(74%), thrombopenia (60%), anemia (55%), fatigue (18%) and vomiting
(13%). Febrile neutropenia was observed in 35% of pts and 1 patient died
of septic shock after cycle 1. Thirty four pts were evaluable for response (4
pts had complete surgery at relapse) and 16 pts responded (4 CR � 12 PR)
(ORR: 47%); 23.5% and 29.4% of the pts had respectively stable and
progressive disease. For all pts (38) and evaluable pts (34), median PFS
were 9.8 and 9.5 months and OS 27 and 25.3 months respectively.
Conclusions: Despite toxicity observed, API is an effective treatment which
compares favorably with other first line therapies for MRULMS pts.
10097 General Poster Session (Board #54B), Sun, 8:00 AM-12:00 PM
Genome-wide analysis and characterization of an online sarcoma cohort.
Presenting Author: Kimberly E. Barnholt, 23andMe, Inc., Mountain View,
CA
Background: Recruitment of an adequately sized cohort for genome-wide
studies presents a serious challenge for rare diseases such as sarcoma.
Traditional barriers to participation include proximity of clinical centers
and motivation or ability to travel. 23andMe’s web-based platform provides
increased accessibility to research participation, facilitating rapid recruitment
of patients (pts) and enabling a large-scale genome-wide association
study (GWAS) of sarcoma. Methods: Sarcoma pts were recruited through
web and email campaigns, patient advocacy groups, physician offices, and
events. Pts provide IRB-approved consent, complete surveys, and receive
updates about research progress through an online account. In collaboration
with an uncompensated panel of academic experts, an online survey
was developed to collect patient-reported data on diagnosis, family history,
symptoms and treatment. Results: This web-based approach has accrued
the largest genotyped, recontactable sarcoma cohort to date. In 20 months,
772 sarcoma pts have enrolled, 683 have been genotyped and 611 have
provided data online. The cohort is primarily of European ancestry (92%),
disproportionately female (72%), with an average age of 51 (� 15 years).
More than 88% of pts indicated a soft tissue sarcoma diagnosis, with
leiomyosarcoma, liposarcoma and “malignant fibrous histiocytoma” being
the most commonly reported subtypes. Over 36% of pts report undergoing
active treatment of some type. Association scans were conducted across a
set of 8,058,452 imputed SNPs, using 568 unrelated sarcoma cases of
European ancestry and �70,000 unrelated population controls from the
23andMe database. Initial results have identified no significant genomewide
associations for general sarcoma risk, despite having �90% power to
detect risk variants with �5% minor allele frequency and odds ratio �2.5,
suggesting the absence of common variants with strong shared effects
across sarcoma subtypes. Conclusions: This pilot study demonstrates
feasibility of rapid recruitment and longitudinal engagement of pts through
online technology. Such techniques may significantly accelerate, and in
some cases fully enable, large-scale genomic studies of sarcoma and other
rare diseases.
TPS10099 General Poster Session (Board #54D), Sun, 8:00 AM-12:00 PM
A phase Ib/II study evaluating the efficacy of doxorubicin (D) with or
without a human anti-PDGFR� monoclonal antibody olaratumab (IMC-
3G3) in the treatment of advanced soft tissue sarcoma (STS). Presenting
Author: William D. Tap, Memorial Sloan-Kettering Cancer Center, New
York, NY
Background: PDGFR� is a receptor commonly overexpressed in STS.
Olaratumab is a fully human IgG1 MAb which specifically binds to human
PDGFR� and blocks PDGFR-mediated signaling pathways. Olaratumab
demonstrated significant tumor inhibition as a monotherapy and in combination
with standard chemotherapy in preclinical human sarcoma xenograft
models. A Phase 1b/2 clinical trial for patients with advanced or
metastatic STS is currently enrolling patients in 9 sites across the United
States; approximately 45 patients have been randomized. Methods: In
Phase 1b, patients received olaratumab (15 mg/kg) via intravenous
infusion on Days 1 and 8 of each 21-day cycle and D (75 mg/m²) 1 hour
after olaratumab on Day 1. Phase 1b was completed without encountering
dose-limiting toxicities; enrollment into Phase 2 has begun. The primary
endpoint of the Phase 2 portion is to compare progression-free survival in
patients with advanced STS when treated with D plus olaratumab versus D
alone. Planned enrollment goal for Phase 2 is 130 patients. Patients are
required to be � 18 years old with ECOG 0-2, have appropriate organ
function and histologically confirmed, measurable, and advanced STS.
There is no restriction on the number of prior therapies. Patients are
randomized 1:1 to either D plus olaratumab (Arm A) at same dose/schedule
as in Phase 1b or D alone (Arm B). All patients can receive dexrazoxane.
Upon completion of 8 cycles, patients in Arm A continue with olaratumab
monotherapy. Patients in Arm B who develop disease progression during or
after treatment can subsequently receive olaratumab monotherapy. Patients
are stratified to treatment arms according to PDGFR� expression
(positive vs. negative), number of previous lines of treatment, sarcoma
subtype, and ECOG performance status. Response assessment occurs
every 6 weeks. Exploratory analyses include biomarkers of olaratumab
pharmacodynamic activity including PDGF ligands, PDGFR downstream
molecules, VEGF, and changes in vascularity of tumor specimens.
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