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cfDNA analysis from phase I/II study of lerociclib (G1T38), a continuously dosed oral CDK4/6 inhibitor, with fulvestrant in HR+/HER2-advanced breast cancer patients
Krastev, B. Rai, R. Bulat, I. Maglakelidze, M. Murias, C. Arkenau, H. T. Baird, R. D. Wardley, Andrew M Roylance, R. Crijanovschi, A.
Krastev, B.
Rai, R.
Bulat, I.
Maglakelidze, M.
Murias, C.
Arkenau, H. T.
Baird, R. D.
Wardley, Andrew M
Roylance, R.
Crijanovschi, A.
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Abstract
Background: Despite significant improvements in progression-free survival for patients
(pts) with HR+/HER2- advanced breast cancer (ABC) treated with approved
CDK4/6 inhibitors combined with fulvestrant, treatment is limited by neutropenia and
gastrointestinal (GI) side effects. Lerociclib, dosed twice daily (BID) with no drug
holiday in combination with fulvestrant, has a favorable safety profile with low rates
of GI adverse events and Grade 3/4 neutropenia, as well as encouraging antitumor
activity in pts with HR+/HER2- ABC (NCT02983071). Cell-free DNA (cfDNA) analysis in
peripheral blood was conducted to characterize mechanisms of response and resistance
in pts that received lerociclib and fulvestrant.
Methods: Pts with pretreated ABC were enrolled across doses of lerociclib 200e650
mg once daily and 100e250 mg BID in combination with fulvestrant 500 mg. Peripheral
blood samples were drawn and cfDNA was isolated at baseline, cycle 1 day
15, each time point when tumor assessments were performed during the treatmentperiod, and at the end of treatment. Samples were analyzed using the Guardant360
platform.
Results: Currently, 58 pts have been evaluated at baseline, with 44 pts (75.9%)
harboring at least one somatic single nucleotide variant (mutation) in the genes
evaluated. Seventeen pts (29.3%) harbored mutations in PIK3CA, with H1047R being
the most common (8/17, 47.1%). Seven pts (12.1%) harbored mutations in ESR1, with
D583G being the most common (4/7, 57.1%). No pts had mutations in both ESR1 and
PIK3CA at baseline. Additionally, 3 pts (5.2%), 2 pts (3.4%), and 1 pt (1.7%) had
mutations in genes at baseline associated with CDK4/6 resistance (RB1, CCND1, and
CCNE1, respectively). Additional analyses of cfDNA (cycle 1 day 15 and end of
treatment) along with correlation of cfDNA dynamics with clinical response are
ongoing and will be presented.
Conclusions: The most common baseline mutations detected were PIK3CA and ESR1.
Additional analyses, including cycle 1 day 15 change from baseline and correlation
with clinical response, are anticipated to help elucidate predictors of response and/or
resistance to the combination of lerociclib and fulvestrant in patients with HR+ ABC.
Description
Date
2020
Publisher
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Keywords
Type
Meetings and Proceedings
Citation
Krastev B, Rai R, Bulat I, Maglakelidze M, Murias C, Arkenau HT, et al. 278MO cfDNA analysis from phase I/II study of lerociclib (G1T38), a continuously dosed oral CDK4/6 inhibitor, with fulvestrant in HR+/HER2- advanced breast cancer patients. Annals of Oncology. 2020;31:S351-S2.