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E-Poster Display

1343P - Correlating osimertinib and erlotinib pharmacokinetics with efficacy and toxicity in EGFR-mutated NSCLC patients (START-TKI study)

Date

17 Sep 2020

Session

E-Poster Display

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

G.D. Marijn Veerman

Citation

Annals of Oncology (2020) 31 (suppl_4): S754-S840. 10.1016/annonc/annonc283

Authors

G.D..M. Veerman1, C.M.J. Steendam2, S.L. Koolen3, E. Oomen-de Hoop4, A.C. Dingemans5, J.G.J.V. Aerts6, R.H. Mathijssen7

Author affiliations

  • 1 Medical Oncology, Erasmus MC - University Medical Center, 3015 GD - Rotterdam/NL
  • 2 Pulmonology, Amphia Hospital, 4818 CK - Breda/NL
  • 3 Medical Oncology, Erasmus MC - University Medical Center, 3015 CE - Rotterdam/NL
  • 4 Medical Oncology Department, Erasmus MC Cancer Institute, 3015 GD - Rotterdam/NL
  • 5 Pulmonology Department, Erasmus MC - University Medical Center, 3015 CE - Rotterdam/NL
  • 6 Department Of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam/NL
  • 7 Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, 3075EA - Rotterdam/NL

Resources

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Abstract 1343P

Background

Osimertinib (OSI) and erlotinib (ERLO) are EGFR tyrosine kinase inhibitors used in NSCLC. For multiple TKIs relationships exist between pharmacokinetic (PK) parameters (e.g. minimal drug concentration or total exposure) and OS or PFS. For ERLO and OSI, no definite target plasma concentrations (C) have been described to optimize their efficacy. PK modelling showed OSI to relate with occurrence of skin rash and diarrhea. We performed an observational cohort study to search for correlations between TKI C and PFS and toxicity.

Methods

Patients were included at start of treatment with first line ERLO or second line OSI. During treatment, PK blood sample collection was performed at every hospital visit to measure ERLO or OSI trough C. The mean C per patient were analyzed by comparing mean C of total treatment duration in total and divided in three equal tertiles per patient. Changes in mean C in the first 6 weeks of treatment were compared with mean C 2 months prior to progression. Primary endpoint was correlation of TKI PK with PFS. Secondary endpoint was correlating TKI PK with toxicity. Cox regression and Kaplan-Meier were used for statistical analysis.

Results

A decrease of 10% or more in mean ERLO C in the second tertile compared to the first tertile of treatment was correlated with a significant shorter PFS (median PFS 8.9 versus 23.6 months; n= 13; p = 0.037). In this group, a significantly shorter time until severe toxicity occurred (median 11.8 versus 23.9 months; p = 0.031) and a trend towards more frequent dose reductions were seen (Chi square 67% versus 29%; p = 0.17). Moreover, ERLO treated patients of whom mean C decreased two months prior to progressive disease compared to mean C of the first six weeks of treatment, had a significantly lower PFS (4.7 versus 7.1 months; n = 5; p = 0.039). C was not correlated with severe toxicity for ERLO (in 67%) or OSI (in 14%).

Conclusions

A decrease in C of ERLO during treatment results in a significant shorter PFS. This suggests a dose-response effect and poses an argument to switch treatment from ERLO to OSI when ERLO C decreases occurs after several months of treatment, or when dose reduction is necessary. Further studies in larger cohorts of patients should confirm these findings.

Clinical trial identification

NL58664.078.16.

Editorial acknowledgement

Legal entity responsible for the study

Erasmus Medical Center.

Funding

Has not received any funding.

Disclosure

C.M.J. Steendam: Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution): AstraZeneca; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Roche. A-M.C. Dingemans: Advisory/Consultancy: Roche. J.G.J.V. Aerts: Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Amphera; Honoraria (self): Eli Lilly; Honoraria (self): Takeda; Honoraria (self): Bayer; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Licensing/Royalties: Amphera; Licensing/Royalties, combination immunotherapy in cancer: Patent pending; Licensing/Royalties, biomarker for immunotherapy: Patent pending. R.H. Mathijssen: Licensing/Royalties, biomarker for immunotherapy: Pamgene patent pending; Advisory/Consultancy: Servier; Honoraria (self): Novartis; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Pamgene; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Servier. All other authors have declared no conflicts of interest.

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