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Anti-PD-1 therapy to overcome trastuzumab-resistant breast cancer - Results of the PANACEA study

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- 7 December 2017 -

 

San Antonio, Texas - The primary results of PANACEA (BIG 4-13 / IBCSG 45-13), an international phase Ib/II trial, suggest that immunotherapy may help overcome trastuzumab-resistant breast cancer.

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As announced yesterday, the first results of PANACEA indicate that the anti-PD-1 antibody pembrolizumab when combined with the existing standard of care, could be a well-tolerated and effective therapeutic approach to overcome trastuzumab resistance in postmenopausal women with advanced HER2-positive breast cancer progressing while on therapy.

The study results were presented by Dr Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, working with the International Breast Cancer Study Group (IBCSG) and study primary investigator, during an oral session at the 2017 San Antonio Breast Cancer Symposium (Texas, USA).

PD-1 pathway and resistance to trastuzumab

Most patients with locally advanced or metastatic HER2+ breast cancer ultimately become resistant to the standard treatment with trastuzumab and their disease progresses. It is therefore essential to develop new treatment strategies.

Both pre-clinical and clinical data suggest that the PD-1/PD-L1 pathway plays an important role in deregulating the immune response to cancer, and that this pathway is probably involved in the resistance to trastuzumab. Evidence supporting this hypothesis is that tumours with high expression of the PD-L1 are often associated with poor patient outcome.

PANACEA was designed to determine if using the anti-PD-1 antibody pembrolizumab (i.e. immunotherapy that inhibits the PD-1 pathway), in combination with the anti-HER2 trastuzumab, can reverse resistance to the standard therapy and improve patient outcome.

Scientists leading this research want to better understand not only the safety and efficacy of this treatment combination, but also the role of the PD-1 pathway in HER2+ breast cancer.

The trial enrolled 58 patients in 11 hospitals from Austria, Australia, France, Belgium and Italy. It is conducted by the International Breast Cancer Study Group (IBCSG), under the Breast International Group (BIG) umbrella. Merck provides drug and funding for this study, which is run according to BIG’s Principles of Research Conduct.

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Read more about PANACEA