medwireNews: Adding the CD73 inhibitor oleclumab to durvalumab plus platinum-doublet chemotherapy does not improve the clinical benefit rate (CBR) among women with treatment-naïve advanced triple-negative breast cancer (TNBC), the SYNERGY investigators have found.
The phase 2 study was terminated early due to the futility boundary being crossed at a prespecified interim analysis, researcher Laurence Buisseret, from Institute Jules Bordet in Brussels, Belgium, told delegates of the ESMO Congress 2022.
She explained to the audience in Paris, France, that “[o]verexpression of the ectoenzyme CD73 is involved in the generation of immunosuppressive adenosine in the tumor microenvironment and is associated with poor prognosis in patients with TNBC.”
The researchers therefore hypothesized that “[b]locking CD73 with oleclumab may enhance the antitumor response” to an anti-PD-L1 agent plus chemotherapy in this setting.
They recruited 127 women with inoperable locally advanced or metastatic TNBC and randomly assigned them to receive durvalumab 1500 mg every 4 weeks alongside weekly carboplatin AUC 1.5 plus paclitaxel 80 mg/m2 either with or without oleclumab 3000 mg given every 2 weeks for five cycles and then every 4 weeks. Chemotherapy was administered for up to 12 cycles, while durvalumab and oleclumab were continued until disease progression or intolerable toxicity.
The primary endpoint of CBR – defined as a complete or partial response or stable disease – at week 24 was a comparable 43% and 44% among patients who did versus did not receive oleclumab, respectively. And there was no significant difference between treatment groups when patients were stratified by PD-L1 or CD73 expression status.
The addition of oleclumab to durvalumab plus chemotherapy also did not significantly improve progression-free survival, at a median of 6.0 months compared with 7.7 months with just durvalumab–chemotherapy.
Buisseret reported that the “safety profile was similar in both arms and adverse events were manageable.”
Looking to the future she said that the “optimal chemotherapy duration with immunotherapy needs to be further investigated and we need to develop new therapeutic combinations” for the treatment of advanced TNBC.
The presenter continued: “We hope that ongoing translational research will shed light on the mechanisms associated with response and resistance to the combination and we hope to identify predictive biomarkers of response.”
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