“We believe that immune evasion is a part of the biological resistance to trastuzumab in patients with this disease,” commented Dr. Loi and colleagues hypothesized that immunotherapy may help to overcome trastuzumab resistance in this subset of breast cancers. It is estimated that approximately 20% of invasive breast cancers are HER2-positive, and some of these patients develop resistance to trastuzumab. “We wanted to investigate if immunotherapy approaches can work in patients with advanced HER2-positive breast cancer that is resistant to trastuzumab,” said Sherene Loi, MD, PhD, Associate Professor at Peter MacCallum Cancer Centre in Melbourne, Australia, working with the International Breast Cancer Study Group (IBCSG).
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No responses were observed in the PD-L1–negative cohort.Ī combination of pembrolizumab (Keytruda) and trastuzumab (Herceptin) tested in patients with trastuzumab-resistant advanced HER2-positive breast cancer was well tolerated and had clinical benefit in patients whose tumors were positive for a biomarker for pembrolizumab, according to data presented from the phase Ib/II PANACEA trial by Loi et al at the 2017 San Antonio Breast Cancer Symposium ( Abstract GS2-06).
In a subgroup of PD-L1–positive patients with 5% or more TILs present in the metastatic lesion, the objective response rate was 39% and the disease control rate was 47%, suggesting that quantification of TILs may help identify patients who will most benefit from this treatment.In the PD-L1–positive intent-to-treat population, the trial met its primary endpoint with an objective response rate of 15% and disease control rate of 25%.