A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2-Positive Metastatic Breast Cancer (CCTG IND.229).
Stephen K L ChiaPhillipe L BedardJohn HiltonEitan AmirKaren GelmonRachel GoodwinDiego VillaMichael CabaneroDongsheng TuMing TsaoLesley SeymourPublished in: The oncologist (2019)
This phase Ib trial with associated correlative endpoints provides insights into the lack of activity of the combination of durvalumab and trastuzumab in heavily pretreated HER2-positive metastatic breast cancer (MBC). No significant clinical activity was observed in patients with heavily pretreated HER2-positive programmed death ligand 1 (PD-L1)-negative MBC with evidence of cytotoxic T-cell exhaustion. Furthermore, all patients had no expression of PD-L1 in the tumor cells. These data support the importance of PD-L1 as an important selection biomarker and the need to assess the tumor microenvironment for immune regulatory cells. Further work is needed to understand how to activate the "cold" tumors to be able to combine current immune-oncology agents.
Keyphrases
- metastatic breast cancer
- end stage renal disease
- phase iii
- study protocol
- clinical trial
- ejection fraction
- chronic kidney disease
- induced apoptosis
- newly diagnosed
- phase ii
- poor prognosis
- palliative care
- peritoneal dialysis
- prognostic factors
- transcription factor
- cell cycle arrest
- electronic health record
- oxidative stress
- epidermal growth factor receptor
- tyrosine kinase
- cell proliferation
- binding protein
- cell death
- data analysis
- artificial intelligence