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TPS1103 aims to extend PFS in HER2-positive breast cancer
Adam Brufsky, MD, PhD, FACP, is a professor of medicine at the University of Pittsburgh School of Medicine. He also serves as associate division chief for the division of hematology/oncology in the University of Pittsburgh School of Medicine's Department of Medicine, medical director of the Magee-Women's Cancer Program, associate director for clinical investigations at UPMC Hillman Cancer Center and codirector of the Comprehensive Breast Cancer Center. Brufsky spoke with Healio about the TPS1103 trial, which will examine the addition of palbociclib to pertuzumab plus trastuzumab and an aromatase inhibitor in patients with HER2-positive, HR-positive breast cancer.
Can you describe what the TPS1103 trial will examine?
The idea behind this trial is a simple one. The question focuses on improving PFS in patients with hormone receptor-positive, HER2-positive disease.
This hypothesis builds on the PERTAIN trial, which examined pertuzumab (Perjeta, Genentech) plus trastuzumab (Herceptin, Genentech and an aromatase inhibitor [anastrozole (Arimidex, AstraZeneca) or letrozole (Femara, Novartis)] in patients with HER2-positive, HR-positive, metastatic/locally advanced breast cancer versus trastuzumab and an aromatase inhibitor alone. The results demonstrated that anastrozole in combination with pertuzumab plus trastuzumab was better than trastuzumab and anastrozole alone.
The question became: Can we make this therapy even better? The next step was to add palbociclib (Ibrance, Pfizer) to the regimen. That’s the idea behind the TPS1103 trial, which is currently enrolling patients. Results are expected in 2020.
How would the addition of palbociclib to the regimen change outcomes in HER2-positive breast cancer?
There is some evidence that CDK4/6 inhibitors like palbociclib can actually enhance the activity of antibody agents like trastuzumab. We’ve already seen a substantial impact when therapy is tripled to include pertuzumab, trastuzumab and an aromatase inhibitor. We hope to make the duration of response even longer, hopefully substantially so. That would make a clinical difference. The idea is to eventually turn HER2-positive breast cancer into more of a chronic disease that people can survive with for a long time.
How would this approach fit into the treatment landscape for HER2-positive breast cancer?
We know that trastuzumab and pertuzumab work well in combination as first-line therapy. CDK4/6 inhibitors add to PFS in triple-positive breast cancer.
We are really working to turn HER2-positive metastatic breast cancer into a chronic disease. Anything we can do to extend OS beyond 5 or 6 years is great. I think the approach in this trial – the addition of palbociclib – is the kind of study that will hopefully achieve that.