160MO - Concomitant medication (conmed) interactions with novel hormonal agents (NHAs) in metastatic castration resistant prostate cancer (mCRPC)

Background

NHAs abiraterone acetate (AA) and enzalutamide (ENZ) are well tolerated in mCRPC but have potential drug interactions, involving cytochrome (CYP) P450 enzymes. Real-world mCRPC patients are often older with polypharmacy risk. We evaluated the impact of conmeds on NHAs in mCRPC.

Methods

We identified patients receiving NHAs within the electronic CRPC Australian Database. Documented conmeds were collected. Conmed interaction categories C (monitor), D (modify) or X (avoid), defined by UpToDate Lexicomp and Stockley’s databases, were considered clinically significant. Baseline characteristics, drug interactions and patient outcomes were analysed.

Results

235 patients received first or second line NHAs for mCRPC (AA n=116, ENZ n=135), with median age 72 years and median 4 conmeds. 44% of patients on AA and 67% on ENZ had clinically significant conmed interactions. Category D and X interactions occurred in 5% and 3% of patients on AA; 19% and 0% on ENZ respectively. Most frequently prescribed interacting drug classes were statins (n=93) and antiplatelets (n=63) (Table). Common interactions reduced conmed concentrations via ENZ CYP3A4 induction (n=83) or increased conmed concentrations via AA CYP2D6 inhibition (n=24). Patients with significant conmed interactions had lower PSA50 response rates with ENZ (50% vs 74%, p=0.04), shorter median overall survival (ENZ 28 vs 45 months, p=0.04; AA 20 vs 26 months) and time to treatment failure (TTF) (ENZ 12 vs 24 months; AA 9 vs 15 months). Those with interactions had more conmeds (median 6 vs 2), but greater conmeds did not correlate with TTF and led to poorer OS in ENZ only. Table: 160MO

Common interacting drug classes and culprit drugs

Conclusions

In our real-world cohort, potential conmed interactions with NHAs were common, involving routinely prescribed drug classes. Poorer outcomes in patients with significant conmed interactions highlight the importance of conmed review in treatment selection.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Associate Professor Ben Tran, principal investigator.

Funding

Electronic CRPC Australian Database receives financial support from Amgen, Astellas, AstraZeneca, Janssen, MSD, Bayer.

Disclosure

A. Anton: Financial Interests, Personal and Institutional, Funding, Consulting, Honoraria: Amgen; Financial Interests, Institutional, Funding: Astellas Pharma, AstraZeneca, Janssen, Mundipharma; Financial Interests, Personal, Other, Honoraria: Eisai, Janssen-Cilag. L. Spain: Financial Interests, Personal, Advisory Board, Chaired Ad Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Invited speaker at COSA (Australian conference): Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory Board 03/2022: Ipsen; Financial Interests, Personal, Stocks/Shares, Stock in Impedimed: Impedimed; Financial Interests, Institutional, Invited Speaker, PROpel study PI for Eastern Health: Astra Zeneca; Financial Interests, Institutional, Invited Speaker, PI for Eastern Health for MDV3800-06: Pfizer; Financial Interests, Institutional, Invited Speaker, PI for Eastern Health for IPATential150 Study: Roche. P. Gibbs: Financial Interests, Personal and Institutional, Funding, Honoraria: Amgen, Merck, Roche; Financial Interests, Institutional, Funding: Bayer, Bristol -Myers Squibb/Sanofi, Pierre Fabre, Roche Molecular Diagnostics; Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal and Institutional, Funding, Honoraria, Travel expenses: Servier; Financial Interests, Personal, Advisory Role: Haystack Oncology. B. Tran: Financial Interests, Personal and Institutional, Funding, Consulting, Honoraria, Travel expenses: Amgen, Astellas Pharma; Financial Interests, Personal and Institutional, Funding, Consulting: AstraZeneca; Financial Interests, Personal and Institutional, Funding, Consulting, Honoraria: Bayer, Janssen-Cilag, Pfizer; Financial Interests, Personal, Funding, Consulting, Honoraria: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Genetech; Financial Interests, Personal, Funding, Consulting: Ipsen, MSD; Financial Interests, Personal, Advisory Role: IQvia, Novartis, Roche Molecular diagnostics; Financial Interests, Personal, Advisory Role, Honoraria: Sanofi, Tolmar. All other authors have declared no conflicts of interest.