1142 - ABCB1 Genetic Polymorphism and Pharmacokinetic Analysis of Low Dose Erlotinib in Frail Patients with EGFR Mutation (mt) -positive, Non-small Cell Lung Cancer: TORG1425

Background

We conducted a trial evaluating the efficacy of low-dose erlotinib (ERL) in frail patients with EGFR-mt non-small cell lung cancer (NSCLC). The primary endpoint was met, with the objective response rate (ORR) of 60% (2018 ASCO Abstr. 9063). Previously, it has been reported that ABCB1 genetic polymorphisms affect pharmacokinetics (PK) of ERL and associated adverse events. We investigated ERL plasma concentration and efficacy, as well as the effects of ABCB1 genetic polymorphisms in the patients who participated in this trial.

Methods

Frail patients with EGFR-mt NSCLC who had not undergone chemotherapy were enrolled and administered 50 mg of ERL. Blood samples were collected prior to treatment for ABCB1 genetic polymorphism testing and at 15 days (±7 days) after initiating ERL administration to measure steady-state trough values. The samples were analyzed at the central laboratory. Plasma concentration was measured with a high-performance liquid chromatograph-tandem mass spectrometery and ABCB1 gene polymorphism analysis using the i-densy^TM genetic testing platform.

Results

Of the patients who participated in the trial between December 2014 and April 2017 (n = 80), ERL plasma concentration could be measured in 48 patients (males/females 17/31; median age 80 (range 49-90); PS 0-1/2/3-4 35/7/6) and genetic analysis in 45 patients. The ORR for low-dose ERL in the 48 patients was 62.5% (CR/PR/SD/PD/NE 1/29/12/3/3), and the median plasma concentration was 685 ng/ml (range 153-1950). ABCB genetic polymorphism analysis results were: C3435T; TT/non-TT 7/38, G2677T/A; TT/non-TT 7/38, C1236T; TT/non-TT 17/28, with all-TT/others: 5/40. The plasma ERL concentrations did not differ according to response: median plasma concentrations (ng/ml) of CR+PR/SD/PD cases were 701/737/590, p = 0.435. Genetic polymorphisms were not correlated with ERL PK, nor were they associated with diarrhea (p = 0.202) or rash (p = 0.29) by Mann-Whitney tests.

Conclusions

In this trial, no clear correlation was observed between ERL PK and efficacy. In frail patients, low-dose ERL administration of 50 mg is effective and safe, regardless of ABCB genetic polymorphisms.

Clinical trial identification

UMIN000015949, release date: 2014/12/15

Legal entity responsible for the study

NPO Thoracic Oncology Research Group.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

T. Tokkito: Chugai Pharmaceutical (Research funding), AstraZeneca (research funding), MSD (research funding). A. Bessho: Chugai Pharmaceutical Co. (honoraria). H. Tanaka: AstraZeneca (research funding, honoraria), Ono Pharmaceutical (research funding, honoraria), Chugai Pharma (research funding, honoraria), Boehringer Ingelheim (honoraria), MSD (research funding, honoraria), Lilly (research funding, honoraria), Taiho Pharmaceutical (research funding, honoraria), Bristol-Myers Squibb Japan (research funding, honoraria), Pfizer (research funding, honoraria), Novartis (honoraria), Takeda (research funding), Astellas Pharma (research funding), Merck Serono (research funding). T. Fukui: AstraZeneca K.K. (honoraria), Boehringer-Ingelheim Japan Inc. (honoraria), Chugai Pharmaceutical Co. Ltd. (honoraria), Novartis Pharma K.K. (honoraria), Ono Pharmaceutical Co. Ltd. (honoraria), Pfizer Japan Inc. (honoraria), Taiho Pharmaceutical Co. Ltd. (honoraria) Y. Hosomi: AstraZeneca (honoraria), Taiho Pharmaceutical (honoraria), Lilly Japan (honoraria), Chugai Pharma Ono Pharmaceutical (honoraria), Bristol-Myers Squibb Japan (honoraria), MSD (honoraria). K. Yamada: Pfizer Japan (honoraria), Chugai Pharmaceutical (honoraria), Eli Lilly Japan (honoraria), AstraZeneca (honoraria), Ono (honoraria). H. Okamoto: Takeda (research funding), MSD (research funding), Ono (research funding), Astrazeneca (research funding), Merck (research funding), Chugai (research funding), Taiho (research funding), Bristol (research funding), Eli Lilly (research funding), Daiich Sankyo (research funding). All other authors have declared no conflicts of interest.