Prof. Laurence Buisseret: SYNERGY Study - Exploration of double immunity combined with chemotherapy in patients with mTNBC

Editor's note: The advent of immunotherapy has seen increased benefits in patients with metastatic triple-negative breast cancer (mTNBC). The SYNERGY study is a randomized, multicenter, open, phase II clinical trial exploring the efficacy and safety of combined immunotherapy with durvalumab + paclitaxel + carboplatin ± anti-CD73 monoclonal antibody oleclumab in the first-line chemotherapy of mTNBC. Oncology Frontier invited Prof. Laurence Buisseret, the principal investigator of the study, from the Jules Bold Institute of the Free University of Brussels, to brief the study results.

 

Oncology Frontier:Could you please tell us about the SYNERGY data and whether oleclumab provides more benefit to patients? What implications does this study bring to us?

 

Prof. Laurence Buisseret: The SYNERGY clinical trials aim to investigate a new combination of chemo-immunotherapy. Currently, in the first-line setting for patients with advanced triple-negative breast cancer (TNBC), treatment is chemotherapy with PD-1/PD-L1 immune checkpoint blockade in patients whose tumors are PD-L1-positive.

 

In the SYNERGY trial, we combined this chemo-immunotherapy with an adenosine targeting agent, oleclumab. This is a monoclonal antibody directed against CD73. CD73 is responsible for the generation of immunosuppressive adenosine in the tumor microenvironment. So the combination of a PD-1/PD-L1 immune checkpoint blocker and this adenosine targeting agent is aimed at enhancing the immune response. Patients were randomized to chemotherapy with paclitaxel and carboplatin received over 12 weeks, and oleclumab, the anti-CD73, with durvalumab, an anti-PD-L1. And in the other arm, patients received the same chemotherapy, but with durvalumab alone. After the 12 weeks of immunotherapy, patients continued with immunotherapy maintenance. The primary endpoint was the clinical benefit at week 24. The trial didn’t show a difference in clinical benefit between the two arms, showing 43% CBR in Arm A with the double immunotherapy, and 44% in Arm B with durvalumab alone.

 

In this study, we show that in unselected TNBC, oleclumab didn't add benefit to the combination of chemo-immunotherapy. But in my opinion, we have to do better research for biomarker and to select TNBC as it is an heterogeneous disease. And it might that we will be able to identify a subset of TNBC patient that might benefit of adenosine targeting agents.

 

Oncology Frontier:Are you optimistic about the treatment prospects of immunotherapy + targeted therapy + chemotherapy in patients with advanced triple-negative breast cancer?

 

Prof. Laurence Buisseret: Recently, targeted therapies with antibody-drug conjugates (ADCs) have shown promising results. I am looking forward to the results of combining ADCs with immunotherapy that might improve the benefits of treatment for TNBC.

 

Oncology Frontier: How should we choose the treatment regimen for patients who progress after immune combined targeted therapy?

 

Prof. Laurence Buisseret: This is a good question. Currently, the treatment option would be ADC, and in the future, ADC plus immunotherapy. We will have to investigate the treatment options for patients who were treated with chemotherapy and immune checkpoint blockers in the neoadjuvant and adjuvant setting. As you may know, the standard-of-care for unselected TNBC who are PD-L1-positive and -negative, is to give immunotherapy in the early setting. We now need to define the treatment options for those patients who relapse and were previously treated with immune checkpoint blockers.