Other concerns are raised by possible differences in disease biology between treatment groups, which may impact on the findings of relatively small studies. Some differences between cohorts in the study arms were noticed; for example, the proportion of patients with undifferentiated pleomorphic sarcoma, an aggressive STS subtype, was higher in the doxorubicin monotherapy arm vs the combination arm (21% vs 15%, respectively). Another imbalance also occurred in the “other” disease category (26% in the combination arm vs 9% in the monotherapy arm), and finally, more women were included in the combination arm (61% vs 51%, respectively). These differences between groups might account for the differences observed in terms of OS.

The effect of olaratumab on the PDGFR pathway also seems to be interesting, even if in the Phase Ib/II study, PDGFRα expression in tumor samples did not show any predictive value on efficacy and, indeed, the authors reported that negative expression of this marker was associated with a favorable outcome, which does not support PDGFRα inhibition in the tumor as the main mechanism of action. However, as confirmed by the authors, the immunohistochemistry assay used to assess PDGFRα expression was not specific; therefore, this issue would require further investigation.

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Olaratumab represents a promising and well-tolerated new anticancer therapy that has demonstrated an unexpected survival benefit in combination with doxorubicin in patients with advanced or metastatic STSs who have poor prognosis. Although in the future this combination seems to have the potential to become the new standard of care for first-line treatment of STS patients, the results of the ANNOUNCE confirmatory Phase III trial are warranted in order to confirm these optimistic perspectives and solve the unanswered questions.


The authors report no conflicts of interest in this work.



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