398P - Drug-induced electrolyte abnormalities in Oncology Phase I Trials: analysis of 1088 cases treated at The Royal Marsden Hospital

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Drug Development
Complications of Treatment
Presenter Alvaro Ingles Garces
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors A.H. Ingles Garces1, J.E. Ang1, M. Ameratunga1, M. Chenard-Poirier1, D. Dolling2, N. Diamantis1, S. Seeramreddi1, R. Sundar1, J. de Bono1, J. Lopez1, U. Banerji1
  • 1Drug Development Unit, The Royal Marsden NHS Foundation Trust, SM2 5PT - London/GB
  • 2Oncology, Institute of Cancer Research Royal Marsden Hospital, SM2 5PT - Sutton/GB

Abstract

Background

The incidence and clinical significance of electrolyte abnormalities (EAs) in phase I studies is not well documented. The objective of this study is to evaluate the incidence of EAs, graded according to CTCAE v4.03, and its correlation with factors influencing them.

Methods

A retrospective chart review was performed of 1088 cases in 82 phase 1 clinical trials consecutively treated from 2011 to 2015 at the Drug Development Unit, The Royal Marsden Hospital. Cox regression was used to examine the relationship between overall survival and baseline characteristics, treating the occurrence of grade 3/4 EAs as a time-varying covariate.

Results

The most common EAs in all grades during trials are: hyponatremia 62%, hypokalemia 40%, hypophosphatemia 32%, hypomagnesemia 17% and hypocalcemia 12%. Overall, grade 3/4 EAs occurred in 19% of cases. More specifically, grade 3/4 EAs were observed, as follow: hyponatremia 10%, hypophosphatemia 6%, hypokalemia 5%, hypomagnesemia 1%, hypermagnesemia 1%. Grade 3/4 EAs occurred during the dose-limiting toxicity window in 8.73% of cases. Overall, diarrhea was associated with hypomagnesemia in all grades (HR 1.78, 95% CI: 1.32-2.39, p 

Conclusions

Baseline EAs are common in patients with advanced cancers participating in phase I trials. This is the first study to demonstrate the clinical significance of baseline hypoalbuminemia and hyponatremia, which are predictors of development of other EAs in phase 1 patients. G3/4 EAs are adverse prognostic factors of OS independent of serum albumin levels.

Clinical trial identification

Legal entity responsible for the study

The Royal Marsden Hospital NHS Foundation Trust

Funding

None

Disclosure

J. de Bono: Consulting or advisory role: Astex, AstraZeneca, Genentech, Genmab, GSK, Merck, Pfizer, Sanofix. Research funding: AstraZeneca, Genentech, GSK, Sanofi, Janssen. U. Banerji: Receipt of grants/research supports: AstraZeneca, Chugai, Onyx, BTG. Receipt of honoraria or consultation fees: Astex, Karus Therapeutics, Novartis, Vernalis. All other authors have declared no conflicts of interest.