Trastuzumab deruxtecan (T-DXd) is highly effective in metastatic HER2+ patients (pts). Elderly pts are underrepresented in trials. The impact of BMI and drug distribution is unclear. Drug-drug interactions (DDIs) can modify the metabolism and toxicity profile. In this multicentric retrospective study, we evaluate outcomes and toxicities in subgroups of pts treated with T-DXd.
HER2+ pts who received T-DXd were included. RECIST 1.1 and CTCAE v5 criteria were used to define response and adverse events (AEs). DDI was evaluated using Drug-PIN® which provides a score and tier (green for no significant DDIs, yellow to red for increasing DDIs). We considered age, HR status, menopausal status, line of treatment, BMI (<25 vs ≥25) and DDIs as relevant features.
143 pts were enrolled. Median(m) age was years 66 (37-84). Elderly pts were: 53% >65y, 35% >70y and 24% >75y. T-DXd was administered as the I/II or further line in 20 and 123 pts (average 4 lines; range 1-11). 75% of pts were HR+. mBMI was 24. mDrug-PIN score was 6.3 (1.7-190). 11, 3 and 2 pts had a yellow, dark yellow and red interaction tier. The ORR was 68% and mPFS was 16 months (mo). mPFS was similar in different age-based groups (>65y p=0.92; >70y p=0.68; >75y p=0.75) and among pre and post-menopausal pts (p=0.79). mPFS in I/II vs subsequent lines was 17 vs 15 mo (p=0.098). HR status did not impact PFS (p=0.078). There was no association between DDi and PFS. BMI>=25 was significantly associated with better PFS (18 vs 13 mo; 12mo-PFS 76% vs 50% p=0.02). Multivariate analysis with BMI and line of treatment, confirms BMI>25 as a biomarker of improved PFS (p=0.023). Most common AE was nausea (32%). AEs and severe AEs were similar among pts with >65y (p=0.15), >70y (p=0.46); >75y (p=0.32). AEs were more common in pts with BMI>25 (70% vs 48% p=0.01) while no association was found with severe AE (p=0.07). Asthenia and nausea were associated with an elevated DDI(score 5 P= 0.001 and p=0.02).
T-DXd is effective and safe in a real-world population and in elderly pts. Pts with BMI>25 have improved PFS. No difference in PFS and AEs was reported according to line of treatment, menopausal status and HR. DDI seems to be associated with specific toxicities such as nausea and asthenia.
Andrea Botticelli.
Has not received any funding.
A. Botticelli: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Lilly, Amgen, Sofos, Gilead, BMS; Financial Interests, Personal, Invited Speaker: MSD, Amgen, BMS. S. Scagnoli: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Roche, Lilly, BMS, MSD. S. Pisegna: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Pfizer, Roche, AstraZeneca. D. Santini: Financial Interests, Personal, Advisory Board: Amgen, Janssen, Astellas, Bayer, Servier, Novartis, MSD, Merck, Pfizer, Ipsen. M. De Laurentiis: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, celgene, Daiichi Sankyo, EIsai, Eli lilly, Exact science, Gilead, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen. R. Caputo: Financial Interests, Personal, Advisory Board: Roche, Lilly, Gilead, Daiichi Sankyo, Pierre-Fabre; Financial Interests, Personal, Invited Speaker: Novartis, MSD. A. Orlandi: Financial Interests, Invited Speaker: Amgen, Pfizer, Daiichi Sankyo; Financial Interests, Advisory Board: Lilly, Novartis, Gilead. M. Palleschi: Financial Interests, Advisory Board: Novartis, Lilly. M.A. Fabbri: Financial Interests, Invited Speaker: Lilly, Roche, Gilead; Financial Interests, Advisory Board: Pfizer, Novartis. G. D'Auria: Financial Interests, Advisory Board: Amgen, Lilly, Eisai, Novartis, Pfizer. P. Marchetti: Financial Interests, Personal, Advisory Role: BMS, Roche, Genentech, MSD, Novartis, Amgen, Incyte, Merck Serono, Pierre-Fabre. A. Fabi: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, Gilead, Sophos, Seagen, AstraZeneca, Lilly, Pierre Fabre, Exact Science. All other authors have declared no conflicts of interest.