Improvements over the past 3 decades in 5-year survival rates for patients with osteosarcoma and Ewing’s sarcoma owe a lot to chemotherapy clinical trials conducted by the Children’s Oncology Group (COG), Mark Agulnik, MD, acknowledged at the Best of ASCO meeting in Chicago. Dr. Agulnik is Associate Professor at Northwestern University, Feinberg School of Medicine, in Chicago.

Treatment for patients with osteosarcomas is currently a “multidisciplinary team effort,” Dr. Agulnik said, including preoperative chemotherapy, limb salvage surgery, and postoperative chemotherapy. “We now have long-term follow-up,” he noted. “In the 70s, you didn’t have that,” he added. Likewise, COG studies have shown continued improvement in survival for patients with localized Ewing sarcoma, so that now more than 75% of patients have event-free survival of 10 or more years.

In general, the use of adjuvant chemotherapy has resulted in “great advances” in the treatment of osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and gastrointestinal stromal tumors, Dr. Agulnik said.

Revised Staging for Soft-Tissue Sarcomas

A major advance in soft-tissue sarcomas has come about through a revised American Joint Committee on Cancer staging system reflecting the importance of grade. “What has become very important is our pathology colleagues providing that information for us,” Dr. Agulnik said. “Without a grade, we can’t stage a patient with sarcoma. We look at grade along with size, location, and extent of disease, whether they have nodal disease or metastatic disease,” he added.

“When we look at our 5-year survival, we see that a low-grade patient with completely surgically excisable disease has a 5-year survival that almost reaches 100%,” Dr. Agulnik reported. “As we go to stage II and stage III, we see that drop off by about 20% in stage II, and then we drop down to about 50% in stage III. We still don’t do well for our stage IV patients,” he noted. For those patients, the 5-year survival is < 20%.

Over the years, the chemotherapy agents for soft-tissue sarcomas have changed, and treatment has been tailored according to the type of sarcoma, Dr. Agulnik stated. Currently indicated agents include dacarbazine for leiomyosarcomas, taxanes for angiosarcomas, vinca alkaloids/topotecan/irinotecan for rhabdomyosarcomas/Ewing sarcomas, temozolomide plus bevacizumab (Avastin) for hemangiopericytomas/solitary fibrous tumors, and methotrexate plus vinblastine/vinorelbine for desmoid tumors.

“The [U.S.] incidence of soft-tissue sarcomas in 2014 is about 12,000, but what is impressive is that there are more than 50 different subtypes. So histology becomes very important, and essentially we need to change our paradigm. We can’t lump all sarcomas together. We need to start splitting them up, and we need to develop treatments specific to the histology,” Dr. Agulnik said.

Proliferation of Targeted Therapies

Summarizing targeted therapy for bone and soft-tissue sarcomas, Dr. Agulnik said that there were “few successes, several failed attempts, some promises, and more work needed.”

Among the agents that have shown some success in specific types of sarcomas are:

• imatinib (Gleevec) for dermatofibrosarcoma protuberans, desmoid tumors, and pigmented villonodular synovitis
• denosumab (Xgeva) for giant cell tumors of bone
• bevacizumab, sunitinib (Sutent), sorafenib (Nexavar), and pazopanib (Votrient) for hemangioendotheliomas/angiosarcomas
• sunitinib and cediranib (investigational) for alveolar soft-part ­sarcoma.

“There are possibilities for each of the separate subtypes,” Dr. Agulnik noted, but “we need more data.” ■