Study suggests immunotherapy may help overcome trastuzumab-resistance in breast cancer

Results from the PANACEA study, recently presented at the San Antonio Breast Cancer Symposium, have suggested that immunotherapy may help to overcome trastuzumab-resistant breast cancer.

“The results of the PANACEA study are very encouraging,” stated Dr Sherene Loi, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, who works with the International Breast Cancer Study Group (IBCSG). “There is a clear need to develop new therapeutic approaches for patients presenting with HER2-positive metastatic breast cancer that has become resistant to trastuzumab. A significant amount of preclinical and correlative clinical data suggest that such cases could be amenable to immunotherapy.”

The PANACEA study is an international Phase Ib/II study that was designed to evaluate the safety and efficacy of using immunotherapy with pembrolizumab in combination with the standard therapy trastuzumab in patients with HER2-positive metastatic breast cancer. The study hypothesis is that pembrolizumab can reverse trastuzumab resistance in patients whose cancer is progressing on trastuzumab.

A total of 58 patients were included in the study, which met its primary objective. All tumours in the study cohort were centrally assessed for HER2 positivity, PD-1 ligand (PD-L1) status, and quantity of tumour-infiltrating lymphocytes (TILs).

“Observations suggest that the PD-1/PD-L1 pathway plays an important role in the trastuzumab resistance that we see in patients with metastatic HER2-positive breast cancer, and the PANACEA study provides proof-of principle evidence that PD-1 inhibition like pembrolizumab can help reverse this,” added Loi. “Moreover, the quantification of TILs seems to be a meaningful way for us to identify those who would benefit most from an immunotherapeutic approach.”