asco@alo33:161855
|
Background: The PARP inhibitorolaparib Lynparza is being evaluated in combination ith other anticancer agents. We investigated the steady-state ss PK effects and safety of olaparib tablet co-administered ith the anti-hormonal agents tamoxifen, anastrozole, or letrozole. Methods: An open-label, nonrandomized study as conducted in 79 eligible patients ith advanced solid tumors. During three consecutive treatment periods, patients received: 1 olaparib 300 mg tice daily bd for 5 days, folloed by a 4-day ashout period; 2 either tamoxifen 60 mg once daily qd for 4 days loading dose then 20 mg qd to day 26 n=30 , or anastrozole 1 mg qd to day 19 n=23 , or letrozole 2.5 mg qd to day 38 n=26 ; 3 same as treatment period 2 concomitantly ith olaparib 300 mg bd for 5 days. Blood samples for PK analysis ere taken at ss. Safety as monitored throughout. Results: Olaparib AUC0-t and Cmax decreased by 27 percent and 20 percent, respectively, hen co-administered ith tamoxifen. Anastrozole and letrozole had no relevant impact on ss exposure to olaparib. Olaparib had minimal effects on ss exposure to tamoxifen, anastrozole or letrozole. Most AEs ere of mild or moderate severity and as expected in this patient population. Conclusions: Exposure to olaparib decreased slightly hen given ith tamoxifen; tamoxifen exposure increased slightly hen given ith olaparib. These effects ere considered unlikely to be clinically significant and no dose adjustments for either drugare required. There ere no drug interactions beteen olaparib and letrozole or anastrozole. Safety data ere consistent ith the knon safety profiles of study drugs. Clinical trial information: lta href=http:clinicaltrials.govshoNCT02093351 NCT02093351ltth class=border-bottom align-left rospan=2 ComparisonReference boundaryx002A;ltth class=border-bottom-broken colspan=2 Cmax GLS mean ratioltth class=border-bottom-broken colspan=2 AUC0-t GLS mean ratioPoint estimate90 percent CIPoint estimate90 percent CIT + O vs O0.71.430.800.710.900.730.630.84A + O vs O0.71.430.940.841.040.890.761.05L + O vs O0.71.431.090.991.211.151.071.25T + O vs T0.71.431.131.061.221.161.111.21A + O vs A0.81.250.900.840.970.860.800.93L + O vs L0.81.250.940.910.980.950.910.99ltfn id=TF-161855-001-1 ltp class=mtgabstract-table-fn x002A;90 percent CIs falling ithin this boundary indicate lack of interaction. Abbreviations: O, olaparib; T, tamoxifen; A, anastrozole; L, letrozole; GLS, geometric least squares.lttable-rap-foot ,J Clin Oncol 34, 2016 suppl; abstr 2562 ,NCT02093351,00:00.0,Developmental TherapeuticsClinical Pharmacology and Experimental Therapeutics
|