Abstract 267P
Background
Abemaciclib demonstrated a clinical benefit in women affected by HR+/HER2- metastatic breast cancer (mBC). Drug-drug interactions (DDIs) can lead to a reduced treatment efficacy or increased toxicity. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the crucial role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. This retro-prospective study aimed to evaluate outcomes, toxicities and DDIs of abemaciclib combined with hormone therapy in a real-world setting.
Methods
Patients (pts) from 12 referral hospitals in Italy, affected by HR+/HER2- mBC who received abemaciclib were included. Availability of clinical data about comorbidities, concurrent medications, outcomes were inclusion criteria. Drug-PIN® was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow, orange, and red) for each pt. Univariate and multivariate analysis were performed to identify early predictors of patients PFS, toxicity or best response (BR).
Results
A total of 173 pts were included. Abemaciclib was administered in combination with fulvestrant or with aromatase inhibitors in 92 and 81 pts, respectively. Overall response rate (ORR) was 62.8%. The median PFS was 28.8 months.The most common toxicities were diarrhoea, asthenia and neutropenia in 63%,49%,49% of pts respectively. Median Drug-PIN score was 3.25 (range 0 -114.8) and 150, 6, 8, 6 and 3 pts were in the green, yellow, dark yellow, orange and red tier, respectively. At the univariate analysis, the number of drugs (p=0.003), the best response (p<0.0001), the high values of Drug-PIN score (p=0.015) and the Drug-PIN tier (from dark yellow to red, p=0.039) were associated with decreased PFS. Correcting for significant variables found at univariate analysis, only the association between BR (p<0.0001), Drug-PIN tier (dark yellow to red, p=0.007) and decreased PFS were confirmed at the multivariate analysis (p<0.0001).
Conclusions
Our study suggests that the concomitant use of multiple drugs is associated with higher toxicity in pts affected by mBC treated with abemaciclib. Moreover, a statistically significant association between decreased PFS and high Drug-PIN score was shown.
Clinical trial identification
Trial protocol number: 0799/2020 Approvated from local CE on Oct/28/2020.
Editorial acknowledgement
Legal entity responsible for the study
Fondazione per la Medicina Personalizzata (FMP).
Funding
Has not received any funding.
Disclosure
A. Botticelli: Financial Interests, Personal, Speaker’s Bureau: Roche, MSD, BMS; Financial Interests, Personal, Advisory Board: Novartis, Amgen, Lilly; Financial Interests, Personal, Invited Speaker: PFIZER. S. Scagnoli: Financial Interests, Personal, Speaker’s Bureau: Novartis, Pfizer, Roche, Lilly, MSD, BMS. S. Pisegna: Financial Interests, Institutional, Invited Speaker: Novartis. A. Toss: Financial Interests, Personal, Advisory Board: Lilly, Pfizer, AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD. A. Fabi: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, Gilead, SOPHOS, Seagen, AstrastraZeneca, Lilly, Pierre Fabre; Financial Interests, Personal, Invited Speaker: EXACT SCIENCE. C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli-Lilly, Roche; Financial Interests, Personal, Advisory Board: MSD, Seagen. G. D'Auria: Financial Interests, Personal, Advisory Board: Amgen, Pfizer, Lilly, Eisai; Financial Interests, Personal, Invited Speaker: Novartis. M.A. Fabbri: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Novartis; Financial Interests, Personal, Speaker’s Bureau: Roche. A. Orlandi: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Gilead, Daichii; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Invited Speaker: Amgen. R. Caputo: Financial Interests, Personal, Speaker’s Bureau: Novartis, Lilly, MSD, Daichii, AstraZeneca; Financial Interests, Personal, Advisory Board: Gilead. P. Vici: Financial Interests, Personal, Advisory Board: Lilly, Eisai, Novartis, Pfizer. M. Palleschi: Financial Interests, Personal, Advisory Board: Novartis, Lilly. G. Tomasello: Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Writing Engagements: Novartis, MercK; Financial Interests, Personal, Invited Speaker: AMGEN; Financial Interests, Personal, Advisory Board: Roche. M. simmaco: Financial Interests, Personal, Other, Scientific Committee Member: Drug PIN. R. Preissner: Financial Interests, Personal, Other, Scientific Committee Member: Drug Pin. E. Cortesi: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Sponsor/Funding: Merck; Financial Interests, Personal, Advisory Role: Astellas, Bayer. P. Marchetti: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Sponsor/Funding: Takeda, Novartis, Incyte; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Other, scientific commitee member: Drug Pin. All other authors have declared no conflicts of interest.