Combination therapy of CDK4/6 inhibitors and endocrine therapies have shown clinical activity in advanced hormone receptor-positive, HER2-negative breast cancer patients whose tumor had previously progressed on endocrine treatment. However, the patients with long-term benefits should be further identified by appropriated biomarkers. Circulating tumor DNA (ctDNA) is a powerful tool for disease monitoring. In this study, the authors used plasma samples from breast cancer patients in the phase III PALOMA-3 trial, which treated patients with palbociclib plus fulvestrant, to analyze the association between the relative change of ctDNA level after treatment and clinical outcome. The ratio of ctDNA level in day 15 to baseline was defined as “circulating DNA ratio” (CDR15). The data showed that patients with a high CDR15 in PIK3CA ctDNA level had a median PFS of 4.1 months and patients with a low CDR15 had a median PFS of 11.2 months, hazard ratio 4.92 (95% CI 1.98–12.26, log-rank test p = 0.0002, q = 0.007). It means that the clinical response of palbociclib and fulvestrant in breast cancer patients could be detected within 2 to 3 weeks by ctDNA tests. These results could be applied in future trials design and clinical disease management.
Source: O'Leary B, Hrebien S, Morden JP, et al. Nat Commun. 2018, 1;9(1):896.