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Top Sarcoma News in 2016

Top Sarcoma News in 2016

  • Dasatinib Offers Little Benefit in Various Sarcoma Subtypes: A phase II trial of dasatinib found that the drug did not produce strong clinical benefit in most types of advanced sarcoma. The trial involved 7 separate cohorts of advanced sarcoma patients divided based on type of sarcoma. It enrolled a total of 200 patients, with 5 of 7 cohorts stopping enrollment early due to a lack of clinical benefit. The median progression-free survival in the full cohort was 1.9 months; progression-free survival ranged from 0.9 months in the 13 rhabdomyosarcoma patients to 2.2 months in the leiomyosarcoma cohort. Median overall survival was 8.6 months in all patients, and ranged from 3.9 months in the rhabdomyosarcoma cohort to 16.6 months for the 11 liposarcoma patients. Image © molekuul_be / Shutterstock.com. Read more.
  • Novel Assay Identifies Potential Ewing Sarcoma Treatments: A novel high-throughput screening assay was used to identify a number of compounds that could potentially offer therapeutic benefit in the bone and soft-tissue tumor known as Ewing sarcoma. The assay specifically targeted genomic regions where the Ewing sarcoma–specific transcription factor EWSR1-FLI1 mediated regions of aberrant nucleosome depletion. The screen included a total of 640 small molecules. Researchers calculated a “relative chromatin inhibition” score measuring the ability to reduce chromatin accessibility at targeted sites, and those compounds with a score more than two standard deviations from the mean were deemed “hits.” There were 58 hits; a secondary screen method with a more stringent threshold identified 15 promising compounds. Image © Hakat / Shutterstock.com. Read more.
  • Analysis Validates Use of PFS As Surrogate Endpoint in Sarcoma Trials: An analysis of randomized controlled trials in soft-tissue sarcoma over a 40-year span found that progression-free survival and response rate are reasonably well correlated with overall survival, and are thus acceptable surrogates to use. Toxicity reporting in these trials is often less than optimal, however. The study included 52 randomized controlled trials including 9,762 patients; 19 of these were published between 1974 and 1993, while the other 33 were published in the last 20 years of the study period. Most of the trials (45 of 52) investigated cytotoxic agents; some had 3 total patient groups, leaving 63 total comparisons in the analysis. The researchers found a highly significant correlation between overall survival and progression-free survival (R = .61), as well as between response rate and overall survival (R = .51). There was no significant correlation between 3-month and 6-month progression-free survival, suggesting these endpoints should be used with caution. Image © SFIO CRACHO / Shutterstock.com. Read more.
  • Older Soft-Tissue Sarcoma Patients Derive More Benefit From Radiotherapy: Older soft-tissue sarcoma patients undergoing surgery derive greater benefit from radiotherapy than younger patients, according to a surprising analysis of more than 15,000 individuals. Most of the patients (59.9%) were treated with surgery alone, and 40.1% were treated with either neoadjuvant (6.8%) or adjuvant radiotherapy (33.3%). The proportion of patients treated with radiotherapy increased over time, from 35.6% in the 1990–1996 period up to 40.1% in the 2007–2011 period. Patients 65 years or older were more likely to be treated with surgery alone (61.4% vs 59.1%; P < .01). For several histologic subtypes, radiotherapy was associated with improved overall survival only in older patients and not in those below the age of 65. Image © adriaticfoto / Shutterstock.com. Read more.
  • Regorafenib Ups Progression-Free Survival in Several Soft-Tissue Sarcomas: Except for patients with liposarcoma, regorafenib is associated with improved progression-free survival in pretreated patients with advanced refractory soft-tissue sarcomas, according to findings from a phase II trial presented at the 2016 American Society of Clinical Oncology Annual Meeting. Participants had been diagnosed with liposarcomas (n = 50), leiomyosarcomas (n = 50), synovial sarcomas (n = 25), and other sarcomas (n = 50). Patients were well-balanced among the eight study groups except in the leiomyosarcoma cohort, in which 50% of patients in the regorafenib arm had grade 3 tumors, compared with 25% of patients in the placebo group. No patients in the study experienced complete response, but 8% of regorafenib-treated patients with synovial sarcoma and 11% of regorafenib-treated patients with other sarcomas experienced partial responses, vs 0 patients in those cohorts’ placebo groups. Image © molekuul_be / Shutterstock.com. Read more.
  • Quality of Life Could Help Select Treatment for Soft-Tissue Sarcoma: Understanding quality of life and the detrimental impact of disease progression is critical for long-term care and survival of patients with soft-tissue sarcoma, according to a study presented at the 2016 American Society of Clinical Oncology Annual Meeting. A total of 452 patients were randomized into this phase III clinical trial. The evaluation included 400 patients with progressive disease: 209 patients in the eribulin arm and 191 patients in the gemcitabine plus dacarbazine (DTIC) arm. Compared with baseline quality-of-life scores, patients on DTIC had significantly lower global health status scores (56.1) compared with those on eribulin (62.1). Physical function, nausea, vomiting, and appetite loss were also significantly worse in the DTIC arm of the trial. Authors noted that the results suggest that health-related quality of life is a relevant consideration when selecting therapies for patients with advanced soft-tissue sarcoma. Image © CHAjAMP / Shutterstock.com. Read more.
  • Genomic Analysis Finds Large Burden of Genetic Risk in Sarcoma Patients: A comprehensive genomic analysis of more than 1,000 sarcoma patients found that about half had putatively pathogenic variations in either known or novel cancer genes. The study aimed to elucidate the specific genetic underpinnings of bone and soft-tissue sarcoma, using samples from 1,162 sarcoma patients in 4 different cohorts. These were compared with 6,545 control subjects from 3 different cohorts. A total of 638 patients (55%) had a total of 956 rare genetic variants; 122 individuals had 127 variants known to be disease causing. Those carrying a variant had a younger age at diagnosis than those without any variant (43 years vs 50 years; P = .0010). Those carrying more dangerous variants had even younger age at diagnosis. A total of 240 patients carried multiple variants, “suggesting a polygenic contribution to sarcoma risk,” according to the authors. Image © gopixa / Shutterstock.com. Read more.
  • Better Imaging Method for Ewing Sarcoma Response Assessment: Functional imaging using FDG-positron emission tomography (FDG-PET) was able to predict response to treatment in Ewing sarcoma patients, and was superior to other anatomic imaging criteria. The retrospective analysis looked at 115 Ewing sarcoma patients in the SARC 011 trial treated with a novel IGF1 receptor antibody, comparing five different imaging criteria using both functional and anatomic imaging. The use of functional imaging criteria, known as PERCIST, identified more patients who responded to the treatment than did any of the four anatomic imaging criteria (volume, WHO local, WHO central, RECIST). Among the 66 patients with interpretable functional imaging and anatomic imaging, 43.9% were responders according to PERCIST, and an average of 21.7% of patients were responders using the anatomic criteria. Those anatomic criteria produced a wide range of those deemed responders, from 21% to 35%, and those deemed progressors, from 12% to 50%. “Use of PERCIST would lead to fewer patients discontinuing therapy,” the authors wrote, also noting that FDG-PET was performed much earlier in treatment and still identified more responders. Image © ballemans / Shutterstock.com. Read more.
  • Olaratumab Is First New Frontline Soft-Tissue Sarcoma Approval in More Than 40 Years: The US Food and Drug Administration granted accelerated approval to olaratumab (Lartruvo) in combination with doxorubicin for the treatment of soft-tissue sarcomas with a histologic subtype that is treatable with anthracycline-containing regimens and that is not amenable to curative treatment with radiotherapy or surgery. The approval was based on results of the JGDG open-label randomized trial, which included 133 patients with a variety of different soft-tissue sarcoma subtypes. Median overall survival was 26.5 months with olaratumab, compared with only 14.7 months without it, for a hazard ratio of 0.52. Median progression-free survival was also numerically better, at 8.2 months with olaratumab compared with 4.4 months with doxorubicin alone. Image courtesy of Eli Lilly and Company. Read more.
  • Maintenance Chemo Fails to Improve Localized Osteosarcoma Outcomes: The use of a metronomic chemotherapy (MC) approach did not improve over standard chemotherapy in patients with high-grade, non-metastatic, operable osteosarcoma of the extremities. In the randomized study, 296 patients with non-metastatic osteosarcomas were randomized to methotrexate, doxorubicin, and cisplatin (MAP) alone for 31 weeks or to MAP followed by 73 weeks of MC with oral cyclophosphamide and methotrexate. The mean event-free survival time was 51.58 months for the MC group, and 58.81 months for the MAP-alone group. The mean overall survival was 65.82 months with MC, and 66.16 months without it, and the hazard ratio for overall survival was 0.985 (P = .957). At 5 years, 76% of MC patients and 73% of MAP-alone patients remained alive (P = .539). The authors noted that although these results do not support the use of metronomic approaches to maintenance therapy in osteosarcoma patients, maintenance therapy in general still deserves further attention based on other research. Image © Chaikom / Shutterstock.com. Read more.

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