Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience

Jana Käthe Striefler,Anne Dörr,Lars Bullinger,Anne Flörcken,Alexander Baur,Daniel Rau,Sven Märdian,Berit Maria Pfitzner,Franziska Brandes,David Kaul,Maren Schmiester,Georgios Koulaxouzidis

doi:10.1186/s12885-020-6551-y

Abstract

BackgroundThe antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). However, recently the phase III ANNOUNCE trial could not confirm the additional value of olaratumab in this context.MethodsHere, in a retrospective analysis we share our single-centre experience with olaratumab/doxorubicin in STS by including n = 32 patients treated with olaratumab/doxorubicin between 2016 and 2019.ResultsMedian progression-free survival (PFS) in the overall cohort was 3.1 months (range 0.6–16.2). A response [complete remission (CR), partial remission (PR) or stable disease (SD)] was seen in n = 11 (34%) cases, whereas n = 21 (66%) patients showed progressive disease (PD). In n = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out of n = 5 patients receiving additional regional hyperthermia, n = 3 achieved PR or SD.ConclusionsThis single-centre experience does also not support the promising phase Ib/II results for olaratumab/doxorubicin in STS. However, our findings do not preclude that olaratumab combination therapy could be valuable in a neoadjuvant setting. This warrants further exploration also taking into account the heterogeneous nature of STS.

Highlights

The antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA)
As PDGFR signalling is known to be relevant in mesenchymal biology [3], a lot of hope was inspired within the STS community based on the promising results of a phase Ib/II trial showing a median
Olaratumab was approved in combination with doxorubicin by the FDA in 2016, especially as there was an improved overall survival (OS) and overall response rate (ORR), which so far had not been documented for any other novel STS treatment

Summary

Introduction

The antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). Olaratumab was approved in combination with doxorubicin by the FDA in 2016, especially as there was an improved overall survival (OS) and overall response rate (ORR), which so far had not been documented for any other novel STS treatment. Hoping that this new approach would be paradigm changing, it seems that many patients have benefitted from the combination treatment since the approval of the drug. The additional value of olaratumab in combination with doxorubicin treatment could recently not be confirmed in the large randomized, double-blind phase III ANNOUNCE trial [5]

Methods

Results

Discussion

Conclusion