Abstract 86P
Background
Acute kidney injury (AKI), defined by the KDIGO Consensus as an increase in serum creatinine of ≧ 0.3 mg/dl or ≧ 1.5 times baseline value, is prevalent in patients treated for cancers secondary to drug-induced toxicities, cancer complication and comorbidities. AKI is associated with poorer prognosis. No data exists on the prevalence of AKI in early-phase oncology trials (EPT), risk factors and impact on patient outcomes.
Methods
We conducted a retrospective study of all patients included in EPT in our institution between 01/2018 and 12/2023. Creatinine levels and glomerular filtration rate (GFR) estimation by Cockroft-Gault (C-G), MDRD and CKD-EPI formulae at baseline and throughout the trial were collected as well as tumor location, age, sex, and time-to-treatment failure (TTF), defined as the time from treatment initiation to the end of treatment date, whatever its reason. The primary endpoint was the AKI rate.
Results
We analysed 2280 inclusions, corresponding to 2025 single patients. Mean age was 60 years and a majority of patients were male. Most of patients were treated for non-small-cell lung cancers (16%) or non-Hodgkin's lymphomas (8%). Baseline MDRD<60ml/min was more prevalent in patients with urothelial, kidney or endometrial cancers (30%, 25% and 24% respectively). We found high concordance between CKD-EPI and MDRD (R=0.89), but low concordance between C-G and MDRD (R=0.57) or CKD-EPI (R=0.61). AKI occurred in 265 (11.6%) inclusions corresponding to 262 patients (12.9%). Median time to AKI was 7.3 weeks. Occurrence of AKI was associated with cancer type (acute leukemia, thyroid, and prostate cancers, p=0.0005) and age (p=0.001) but not with lower baseline GFR, whatever the formula used. AKI and lower baseline GFR were not associated with poorer TTF (HR: 0.68 - p<0.001 and 0.76 - p=0.026 for AKI and CKD-EPI GFR < 60 mL/min respectively).
Conclusions
AKI is common in patients included in EPT but cannot be predicted using baseline GFR. AKI and lower baseline GFR are not associated with worse TTF. Our results, argue for the use of MDRD and/or CKD-EPI rather than C-G for baseline GFR estimation in the inclusion/exclusion criteria and for less stringent thresholds. A closer monitoring of kidney function throughout EPT is needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, Seattle Genetics, Taiho; Financial Interests, Personal, Other, lectures, Advisory Boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, Advisory Boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Invited Speaker: Janssen, Pfizer, Janssen, MSD, Janssen, Exelexis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Astellas, Gilead/Immunomedics, Basilea, Taiho; Non-Financial Interests, Personal, Member: ESMO, ASCO, AACR; Non-Financial Interests, Personal, Other, Scientific committee: ARC. C.P. Massard: Other, Personal, Other, Christophe Massard: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Netcancer, PegascyPrincipal/sub-Investigator of Clinical Trials for AbbVie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo Pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 Biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, MedImmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. All other authors have declared no conflicts of interest.