CHICAGO – Patients with high-risk soft-tissue sarcomas identified by patient data and a risk calculator had significantly better overall and disease-free survival when they were treated with adjuvant doxorubicin and ifosfamide, a retrospective analysis from a randomized clinical trial showed.
The findings suggest that future clinical trials for sarcoma therapies may need to focus on specific risk categories, investigators said.
Among 290 patients with soft tissues sarcomas (STS) of the trunk wall or extremities, adjuvant chemotherapy with doxorubicin, ifosfamide, mesna, and lenograstim more than halved the risk of death for patients determined by the nomogram to have a low probability of 10-year overall survival, reported Sandro Pasquali, MD, from the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, and his colleagues.
“These findings interpret conflicting results of randomized controlled trials on perioperative chemotherapy in STS showing that inclusion of low-risk tumors have diluted the effect of chemotherapy leading to negative results and small study effect in meta-analysis,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.
The clinical trial in question, EORTC-STBSG 62931, results of which were published in 2012 in The Lancet Oncology, was technically a failure, because it did not show a significant benefit of adjuvant chemotherapy vs. observation in patients with STS.
To see whether adjuvant chemotherapy may have benefited select patients, the investigators calculated 10-year probabilities of overall survival (P-OS) for 290 patients with STS of the trunk wall or extremities out of the total trial cohort of 351 patients. The P-OS for each of three categories – low (51% or less), intermediate (52%-66%), and high (67% or greater) – was calculated using individual patient data and the freely available smartphone-based nomogram Sarculator (available in the Apple App Store and Google Play).
They calculated disease-free survival at the study median follow-up of 8 years.
The tumor histologies included malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and others.
A total of 52 patients were in the low P-OS group, including 24 treated with observation, and 28 with adjuvant chemotherapy. Respective numbers for the intermediate and high P-OS categories were 34/34, and 90/80.
The investigators found that for patients in the low P-OS group, adjuvant chemotherapy cut the risk of death by slightly more than half, with a hazard ratio of 0.46 (P = .033). In contrast, there were no significant differences in the risk of death for patients at either intermediate or high probability of 10 year OS (HR, 1.00 and 1.08, respectively; P values not significant).
Similarly, adjuvant chemotherapy cut the risk of disease progression by the same amount, with an HR of 0.46 (P = .021), whereas there was no additional benefit among patients at either intermediate or high probability of 10-year OS (HR 0.74 and 0.90; P values were not significant).
The absolute risk reduction for adjuvant chemotherapy was 21% (8-yr disease-free survival of 34% for adjuvant chemotherapy vs. 13% for observation), with a number needed to treated of 4.76.
The study was supported by the European Organization for Research and Treatment of Cancer. Dr. Pasquali reported having no conflicts of interest.