1406P - Outcomes of patients with metastatic EGFR mutant lung cancer requiring dose modifications of first line osimertinib

Background

Osimertinib is a standard first line treatment for advanced EGFR mutant lung cancer. While EGFR tyrosine kinase inhibitors are generally well tolerated, side effects, including diarrhea and rash, are common and often require dose modifications. The impact of osimertinib dose modification on survival outcomes is not known.

Methods

Patients with metastatic EGFR mutant lung cancer who received first line osimertinib between 2020 and 2022 were retrospectively identified using pharmacy records in British Columbia, Canada. Patient charts were reviewed to determine the incidence of dose reductions or treatment cessation of osimertinib due to toxicity. The type of toxicity leading to the treatment modification was also recorded. The median time to treatment discontinuation (mTTD) and the median overall survival (mOS) of patients requiring dose modification was compared to those who did not require modification using Kaplan Meier analysis and log rank testing.

Results

The analysis identified 311 patients and with a median follow up time of 26 months. 72 (23%) patients required a dose modification due to toxicity. At time of analysis, 52/72 (72%) of the dose modification group had stopped osimertinib vs 142/239 (60%) in the no modification group. The most frequent toxicities leading to dose reduction or cessation included diarrhea (17), skin toxicity (13), respiratory symptoms (10), anorexia (9), and cardiotoxicity (6). Pneumonitis occurred in 9 patients (3% of the study population). Twenty patients ultimately discontinued osimertinib due to toxicity. The mTTD was shorter in the dose reduction group, 14.3 months (95%CI 11.0-21.3) vs 21.9 months (95%CI 16.9-24.5) in the no reduction group (p=0.042). Second line treatment was received by 19/52 (35%) in the dose modification group and 59/145 (42%) in the no modification group. The mOS of patients requiring dose modifications was 27.6 months (95% CI 21.1-34.1), which was similar to patients not requiring dose modifications, mOS 26.8 months (95% CI 21.9-33.1), p=0.868.

Conclusions

Nearly one quarter of patients treated with osimertinib required a dose reduction or treatment cessation. Despite this, dose modifications did not lead to worse mOS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Ho: Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Janssen, Jazz, Merck, Novartis, Pfizer, Roche, Takeda. B. Melosky: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca Canada, Bristol Myers Squibb, Roche, Pfizer, Johnson and Johnson, Novartis, Amgen. J. Laskin: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche Canada, Pfizer, Jazz, AstraZeneca. Y. Wang: Financial Interests, Personal, Speaker, Consultant, Advisor: Takeda, Merck, AstraZeneca. S. Sun: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, Takeda. All other authors have declared no conflicts of interest.