Aditya Bardia, MD, MPH

Aditya Bardia, MD, MPH, Assistant Professor of Medicine at Harvard Medical School and Director of Precision Medicine at the Center for Breast Cancer, Massachusetts General Hospital, Boston, found the PALLET study noteworthy in light of heightened interest in cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. “This important trial demonstrated no differences in response rates with the addition of neoadjuvant palbociclib to an aromatase inhibitor, which initially appears a bit counterintuitive because in the metastatic setting, the combination is clearly better,” he told The ASCO Post.

“Three factors need to be considered,” Dr. Bardia continued. “First, the method of response assessment, ie, by ultrasound, pathologic complete response might not be sensitive enough in estrogen receptor–positive disease. Second, the study did demonstrate an improvement in Ki67, which is a validated surrogate biomarker for long-term outcomes with endocrine therapy, though whether the surrogacy also holds for other therapies such as CDK4/6 inhibitors is not clear. Third, the authors report a decrease in apoptosis with combination therapy, which likely speaks to the mechanism of action of CDK4/6 inhibitors in blocking cell-cycle arrest and proliferation, and results might have implications for use of CDK4/6 inhibitors in the adjuvant setting. Overall, this is a very important study that sheds light on tumor biology, pharmacodynamic biomarkers, and a role for neoadjuvant studies in estrogen receptor–positive breast cancer.” ■

DISCLOSURE: Dr. Bardia has financial ties including consulting or advisory roles with Genentech/Roche, Immunomedics, Novartis, Pfizer, Merck, Radius Health, Spectrum Pharma, and Taiho Pharma; institutional research funding from Novartis, Pfizer, Genentech, Merck, Radius Health, Immunomedics, Mersana Pharma; and a research grant from Biotheranostics.