Highlights of Day I – Bone tumors and soft tissue sarcomas
Shreyaskumar Patel, M.D.
Sarcoma Center Medical Director
Professor of Medicine
Deputy Chairman – Dept of Sarcoma Medical Oncology
MD Anderson Cancer Center, Houston, TX
Dr. Patel serves on the board of directors for SARC.
On the morning of the second day of the ASCO meeting, Dr. Patel presented a summary of the sarcoma presentations that took place the previous day. Below are the highlights covered.
Bone Tumors
“Denosumab treatment of giant cell tumor of bone: Interim analysis of an open-label phase 2 study”
Presented by Dr. David Thomas and colleagues
GCTs, or Giant cell tumors, are osteolytic lesions. These tumors are composed of osteoclast-like giant cells over-expressing RANK ligand. Denosumab, an IgG2 isotype, is a fully human monoclonal antibody with a high affinity and specificity for RANK ligand. Doses given intravenously were well tolerated, with mostly grade I toxicities. The treatment also exhibited an impressive level of activity. Many patients showed clear clinical benefit and some experienced disappearance of giant cells. There was also radiographic evidence of response with reconstitution of bone and healing.
“Randomized comparison of every 2 week vs. every 3-wk chemotherapy in Localized Ewing Sarcoma Family Tumors (ESFT)”
Presented by: Dr. Womer and colleagues for COG
This trial is a comparison of two chemotherapy regimens involving alternating doxorubicin & cyclophosphimide and etoposide & ifosfamide. Response differences were evaluated between two different schedules: the standard or conventional cycle – given at 3 week intervals – and a compressed cycle – given at 2 week intervals. There does seem to be an improvement in event free survival at 3 years in favor of the compressed dosing schedule. This difference is more noticeable for the non-adult population despite no difference in tolerance among the age groups.
IGF-1 Pathway
There are currently 6 different antibodies targeting this receptor in phase testing. Dosage and specific targets varies for each.
“Safety, pharmacokinetics and preliminary activity of the anti IGF-IR antibody CP-751871 in patients with sarcoma”
This is a phase 1 Pfizer study. This antibody was given intravenously at 3 (or for younger patients at 4 week) intervals. This trial yields clear biologic and clinical activity in EFST. This pathway will remain an active area of research over the next few years.
Soft Tissue Sarcoma
“Prognostic and predictive factors for outcome to first-line Ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas treated in EORTC-STBSG studies”
The EORTC evaluated activity of ifosfamide (or doxorubicin and ifosfamide) across multiple studies. They focused on the relationship between prognostic factors and response rate. Covariables included performance status, histological subtype, locally advanced or metastatic disease, gender, histopathological grade, and primary tumor site. The conclusions drawn suggest coupling ifosfamide with doxorubicin is clearly preferred in many subtypes. Findings also supported the idea that leiomyosarcoma and liposarcoma benefit less from IFM-containing therapy when compared to doxorubicin.
“A FNCLCC French Sarcoma Group – GETO multicenter randomized phase II study of Gemcitabine (G) versus Gemcitabine and Docetaxel (G+D) in patients with metastatic or relapsed leiomyosarcoma (LMS)”
A TAXOGEM study
Presented by: F. Duffaud and colleagues
Results suggest the combination of gemcitabine and docetaxel is superior in response rate, progression free survival, and overall survival as a second line therapy in patients with LMS.
When compared to a SARC study presented at ASCO 2 years ago, there were a few differences in median progression free survival. These differences could be due to administration schedule. When comparing PFS for 3 and 6 months, the 2 studies are comparable. This study suggests a movement towards treating leiomyosarcomas with a regimen of gemcitabine and docetaxel, instead of a more toxic one with Ifosfamide and doxorubicin. It provides more information to support movement towards histology specific therapy.
“Synovial sarcoma: A retrospective analysis of 250 patients treated at the Rizolli institute”
Majority of patients with synovial sarcomas exhibit an exon 18 translocation – either syt-ssx1 or syt-ssx2. The specific mutation makes a difference in terms of response to therapies.
“Combination therapy with temozolomide and bevacizumad in the treatment of hemangiopericytoma/malignant solitary fibrous tumor (HPC/SFT)”
This is a clinical trial at MD Anderson Cancer Center. This study deals with a rare variant of tumor that currently has no active systemic therapy. It also evaluates response rates after alternating cyclic administration of temozolomide and bevacizumab. Level of activity was measured by CHOI criteria. Results suggests there is evidence of biologic activity.
Gastro-Intestinal Stromal Tumor
“Insulin-like growth factor 1 receptor (IGF-1R): A potential therapeutic target for gastrointestinal Stromal tumors (GIST)”
This trial was open at Fox Chase Cancer Center. This is another study dealing with the IGF-1 pathway. This treatment shows a decreased cell survival in GIST patients. More trials in development to study this further.
“Results from phase 1 trial of IPI-504, a Novel HSP90 Inhibitor, in Tyrosine Kinase Inhibitor-Resistant GIST and other sarcomas”
This is a trial of IPI-504 in GIST patients that have not responded to the 2 standard kinase inhibitors (imatinib (Gleevec) and sunitinib (Sutent)). Only modest response activity was seen but enough stabilization of disease was observed such that the clinical benefit rate is of interest. A limitation may be the durability of this treatment – it is short with a median progression free survival of only 12 weeks.
“Sorefenib is active in pts with imatinib and sunitinib-resistant GIST: A phase II trial of the U of Chicago Phase II consortium”
This is a trial of 3rd line therapies for GIST patients. Some signal of activity was seen in imatinib resistant and sunitinib resistant patients treated with sorefenib. The clinical benefit seen is fairly impressive but again, the durability of this treatment is short.