CDK4/6 inhibitor NLR

The PALOMA-2,3 study are randomized multicenter trials to test the efficacy and safety of Palbociclib in combination with endocrine therapy in advanced estrogen receptor (ER) + breast cancer patients, and showed superior efficacy of palbocicilb combination therapy compared to endocrine monotherapy. The cyclin dependent kinase (CDK) 4/6 selective inhibitor, palbociclib showed robust clinical benefit as both front-line (PALOMA-2) and later-line (PALOMA-3) therapy in ER+ breast cancer patients. However, the resistance to palbociclib develops after 2 years of therapy in average, and reliable clinical predictors are needed to predict palbociclib response. Recent studies showed that CDK4/6 inhibitor exhibit anti-tumor effect not only by inducing cell cycle arrest, but also by modifying tumor microenvironment and promoting anti-tumor immune response. In the preliminary analysis of palbociclib-treated patients in our institution (Yonsei Cancer Center), The high neutrophil-to-lymphocyte (NLR) ratio after 1 cycle of palbociclib treatment was significantly associated with progression-free survival of palbociclib + endocrine therapy, demonstrating immunologic biomarkers from peripheral blood can predict palbociclib response. It would be a significant advance if we can predict favorable and durable response to palbociclib using NLR in peripheral blood analysis. We propose a pooled analysis of palbociclib phase III trials (PALOMA-2 and PALOMA-3) to establish peripheral NLR or lymphocyte count as predictors for palbociclib response. The results of this study will affect treatment of all ER+ advanced breast cancer patients world wide, approxmately 300,000~400,000 patients per year worldwide and 20,000~30,000 patients per year in US. If the result can affect the adjuvant CDK4/6 treatment in the future, the result will affects ~ 1,000,000 cases worldwide ~100,000 cases in US every year.