Predicting sensitivity to palbociclib with early circulating tumor DNA dynamics in the PALOMA-3 trial.

• DOI: 10.1200/jco.2017.35.15_suppl.1018
• Publication Date: 2018-09-06T15:38:57Z
• Authors: Ben O'Leary; Sarah Hrebien; James P Morden; Matthew Beaney; Yuan Liu; Cynthia Huang Bar...; Maria Koehler; Massimo Cristofan...; Isaac Garcia-Muri...; Judith Bliss; Nicholas C. Turner
• Keywords: Palbociclib; Fulvestrant

1018 Background: Palbociclib improves progression free survival (PFS) in patients with advanced, hormone receptor positive, HER2-negative breast cancer. There are currently no biomarkers to predict sensitivity palbociclib. We investigated if early circulating tumour DNA (ctDNA) dynamics could clinical outcome on palbociclib (Palbo) and fulvestrant (F) the PALOMA-3 trial. Methods: Plasma samples were prospectively collected for ctDNA analysis at baseline, cycle 1 day 15 (D15) end of treatment (EOT), screened PIK3CA ESR1 mutations using digital PCR. The primary objective was assess whether dynamic changes would PFS treated Palbo + F. Suppression levels below an optimised cut-off D15, relative baseline levels, termed a ‘circulating ratio (CDR) response. Results: identified 22.0% (100/455) 52 these randomised F having matched D15 samples. Patients CDR response had median 11.2 months (95%CI 11.1 – undefined) whereas without 4.1 3.6 5.5) (HR 4.92, 95% CI 1.98 12.26, p = 0.0002). Overall, suppressed greater extent than placebo (p<0.0001). 25.6% (114/445) samples, 65 showed suppression mutations, more frequently undetectable EOT (25.8% 8/31, v 2.6% PIK3CA, 1/38, p=0.004). Clearance mutation associated loss ESR1at (p 0.027). Conclusions: Early tumor assessment may fulvestrant, validated by further allow be adapted prior progression. lost after fulvestrant.